Nutrient chapter

L-Carnitine

Independent small molecule record; interpretation is limited by each linked claim and its study context.

88 recorded mechanisms · 6 availability situations · 9 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Expressing human ALDH9 in bacteria produced NAD+-dependent trimethylaminobutyraldehyde dehydrogenase activity, completing the aldehyde-to-gamma-butyrobetaine step.
ALDH9A1 → gamma-Butyrobetaine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human ALDH9 compared with purified and recombinant rat enzyme.
limitations
NAD+ dependence does not establish benefit from niacin supplementation.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A niacin-derived coenzyme participates in making carnitine.
primary_references
Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10702312/ · DOI 10.1074/jbc.275.10.7390
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 18–24
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human ALDH9 compared with purified and recombinant rat enzyme. · source_derived_draft · unverified_draft
## l-carnitine-aldehyde-step A niacin-derived coenzyme participates in making carnitine. Expressing human ALDH9 in bacteria produced NAD+-dependent trimethylaminobutyraldehyde dehydrogenase activity, completing the aldehyde-to-gamma-butyrobetaine step. Model: Recombinant human ALDH9 compared with purified and recombinant rat enzyme. Limitations: NAD+ dependence does not establish benefit from niacin supplementation. Evidence access: Primary abstract Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10702312/ · DOI 10.1074/jbc.275.10.7390
Complete structured claim and evidence
Human tissue assays detected gamma-butyrobetaine-to-carnitine activity in liver, kidney and brain, but not heart or skeletal muscle; the earlier steps were detected in all five tissues.
gamma-Butyrobetaine → Human tissue carnitine biosynthetic enzyme activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human tissue homogenate enzyme assays.
limitations
Detection limits, developmental stage and sampled tissues constrain the result; not an absolute modern atlas.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Some tissues rely on importing the finished molecule.
primary_references
Tissue distribution of carnitine biosynthetic enzymes in man. · 1980 · https://pubmed.ncbi.nlm.nih.gov/6770910/ · DOI 10.1016/0304-4165(80)90133-6
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 26–32
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human tissue homogenate enzyme assays. · source_derived_draft · unverified_draft
## l-carnitine-tissue-synthesis Some tissues rely on importing the finished molecule. Human tissue assays detected gamma-butyrobetaine-to-carnitine activity in liver, kidney and brain, but not heart or skeletal muscle; the earlier steps were detected in all five tissues. Model: Human tissue homogenate enzyme assays. Limitations: Detection limits, developmental stage and sampled tissues constrain the result; not an absolute modern atlas. Evidence access: Primary abstract Tissue distribution of carnitine biosynthetic enzymes in man. · 1980 · https://pubmed.ncbi.nlm.nih.gov/6770910/ · DOI 10.1016/0304-4165(80)90133-6
Complete structured claim and evidence
Single oral L-carnitine doses had estimated bioavailability of 16% at 2 g and 5% at 6 g, with similar plasma exposure despite the higher dose.
L-Carnitine → Human oral supplemental carnitine bioavailability source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six healthy adults on a low-carnitine diet; oral and IV comparisons.
limitations
Supplement boluses do not establish food bioavailability or tissue loading.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A larger oral dose did not yield proportionally more circulating carnitine.
primary_references
Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects. · 1988 · https://pubmed.ncbi.nlm.nih.gov/3220097/ · DOI 10.1007/BF00555510
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 34–40
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six healthy adults on a low-carnitine diet; oral and IV comparisons. · source_derived_draft · unverified_draft
## l-carnitine-oral-dose A larger oral dose did not yield proportionally more circulating carnitine. Single oral L-carnitine doses had estimated bioavailability of 16% at 2 g and 5% at 6 g, with similar plasma exposure despite the higher dose. Model: Six healthy adults on a low-carnitine diet; oral and IV comparisons. Limitations: Supplement boluses do not establish food bioavailability or tissue loading. Evidence access: Primary abstract Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects. · 1988 · https://pubmed.ncbi.nlm.nih.gov/3220097/ · DOI 10.1007/BF00555510
Complete structured claim and evidence
Human OCTN2 transport measurements were consistent with approximately one sodium ion accompanying each carnitine molecule.
Human carnitine transporter OCTN2 / SLC22A5 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human OCTN2 expressed in HEK293 cells.
limitations
Does not imply that eating more salt improves carnitine uptake.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Cell entry depends on a sodium-coupled transporter.
primary_references
Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
transport_effect
raises Sodium-coupled, with about one sodium ion accompanying each carnitine molecule inward.
transport_pool
the expressing cell Sodium-coupled, with about one sodium ion accompanying each carnitine molecule inward.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 42–48
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human OCTN2 expressed in HEK293 cells. · source_derived_draft · unverified_draft
## l-carnitine-octn2-sodium Cell entry depends on a sodium-coupled transporter. Human OCTN2 transport measurements were consistent with approximately one sodium ion accompanying each carnitine molecule. Model: Human OCTN2 expressed in HEK293 cells. Limitations: Does not imply that eating more salt improves carnitine uptake. Evidence access: Primary abstract Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
Complete structured claim and evidence
Expressed human OCTN2 transported acetyl-L-carnitine in a sodium-dependent manner with a measured Km of 8.5 micromolar.
Human carnitine transporter OCTN2 / SLC22A5 → Acetyl-L-carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human OCTN2 in HEK293 cells.
limitations
A kinetic constant is not a treatment target.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The transporter also carries the acetylated form.
primary_references
Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
transport_effect
raises Sodium-dependent acetylcarnitine transport with a measured Km of 8.5 micromolar.
transport_pool
the expressing cell Sodium-dependent acetylcarnitine transport with a measured Km of 8.5 micromolar.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 50–56
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human OCTN2 in HEK293 cells. · source_derived_draft · unverified_draft
## l-carnitine-octn2-acetyl The transporter also carries the acetylated form. Expressed human OCTN2 transported acetyl-L-carnitine in a sodium-dependent manner with a measured Km of 8.5 micromolar. Model: Human OCTN2 in HEK293 cells. Limitations: A kinetic constant is not a treatment target. Evidence access: Primary abstract Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
Complete structured claim and evidence
Human OCTN2 transported D-carnitine with lower affinity than L-carnitine: reported Km values were 10.9 versus 4.3 micromolar.
D-Carnitine → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Transporter expression assay.
limitations
D-carnitine is an experimental comparator, not a substitute.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The two mirror-image molecules are handled differently.
primary_references
Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 58–64
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Transporter expression assay. · source_derived_draft · unverified_draft
## l-carnitine-octn2-stereo The two mirror-image molecules are handled differently. Human OCTN2 transported D-carnitine with lower affinity than L-carnitine: reported Km values were 10.9 versus 4.3 micromolar. Model: Transporter expression assay. Limitations: D-carnitine is an experimental comparator, not a substitute. Evidence access: Primary abstract Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
Complete structured claim and evidence
Fibroblasts carrying truncating OCTN2 variants from two unrelated patients lacked mediated carnitine transport.
Human carnitine transporter OCTN2 / SLC22A5 → Human OCTN2-mediated cellular carnitine transport source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human primary-carnitine-deficiency patient fibroblasts and variant expression.
limitations
Genetic transport failure differs from low dietary intake.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A broken cell-entry mechanism can produce primary carnitine deficiency.
primary_references
Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10051646/ · DOI 10.1073/pnas.96.5.2356
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 66–72
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human primary-carnitine-deficiency patient fibroblasts and variant expression. · source_derived_draft · unverified_draft
## l-carnitine-octn2-loss A broken cell-entry mechanism can produce primary carnitine deficiency. Fibroblasts carrying truncating OCTN2 variants from two unrelated patients lacked mediated carnitine transport. Model: Human primary-carnitine-deficiency patient fibroblasts and variant expression. Limitations: Genetic transport failure differs from low dietary intake. Evidence access: Primary abstract Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10051646/ · DOI 10.1073/pnas.96.5.2356
Complete structured claim and evidence
Transfecting patient fibroblasts with normal OCTN2 cDNA partially restored carnitine transport.
Human carnitine transporter OCTN2 / SLC22A5 → Human OCTN2-mediated cellular carnitine transport source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Patient fibroblast gene-complementation experiment.
limitations
This is experimental gene complementation, not a clinical gene-therapy result.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Replacing the missing transport function rescued uptake in cells.
primary_references
Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10051646/ · DOI 10.1073/pnas.96.5.2356
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 74–80
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Patient fibroblast gene-complementation experiment. · source_derived_draft · unverified_draft
## l-carnitine-octn2-rescue Replacing the missing transport function rescued uptake in cells. Transfecting patient fibroblasts with normal OCTN2 cDNA partially restored carnitine transport. Model: Patient fibroblast gene-complementation experiment. Limitations: This is experimental gene complementation, not a clinical gene-therapy result. Evidence access: Primary abstract Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10051646/ · DOI 10.1073/pnas.96.5.2356
Complete structured claim and evidence
In a reported patient with homozygous SLC22A5-associated primary carnitine deficiency and a cardiac presentation, cardiac function remained normal during 14 years of oral carnitine treatment.
L-Carnitine → Human cardiac function in primary carnitine deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Single human case and long-term follow-up.
limitations
One case, no untreated comparator; not proof of general cardiovascular benefit.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Treating a confirmed transport disorder can have a different role from general supplementation.
primary_references
Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26030785/ · DOI 10.1515/jpem-2014-0528
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 82–88
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Single human case and long-term follow-up. · source_derived_draft · unverified_draft
## l-carnitine-primary-heart Treating a confirmed transport disorder can have a different role from general supplementation. In a reported patient with homozygous SLC22A5-associated primary carnitine deficiency and a cardiac presentation, cardiac function remained normal during 14 years of oral carnitine treatment. Model: Single human case and long-term follow-up. Limitations: One case, no untreated comparator; not proof of general cardiovascular benefit. Evidence access: Primary abstract Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26030785/ · DOI 10.1515/jpem-2014-0528
Complete structured claim and evidence
Human CPT1B expressed in yeast catalyzed transfer from palmitoyl-CoA onto carnitine, forming palmitoylcarnitine and releasing CoA.
Human carnitine palmitoyltransferase 1B / CPT1B → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and reviewed UniProt catalytic-reaction record
experimental_model
Human heart/muscle isoform in Pichia mitochondria; canonical reaction also recorded in UniProt Q92523/Rhea 12661.
limitations
This isoform assay does not measure whole-body fat loss.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The outer-membrane enzyme loads a fatty-acid group onto carnitine.
primary_references
Functional studies of yeast-expressed human heart muscle carnitine palmitoyltransferase I. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9344464/ · DOI 10.1006/abbi.1997.0314
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 90–96
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human heart/muscle isoform in Pichia mitochondria; canonical reaction also recorded in UniProt Q92523/Rhea 12661. · source_derived_draft · unverified_draft
## l-carnitine-cpt1-transfer The outer-membrane enzyme loads a fatty-acid group onto carnitine. Human CPT1B expressed in yeast catalyzed transfer from palmitoyl-CoA onto carnitine, forming palmitoylcarnitine and releasing CoA. Model: Human heart/muscle isoform in Pichia mitochondria; canonical reaction also recorded in UniProt Q92523/Rhea 12661. Limitations: This isoform assay does not measure whole-body fat loss. Evidence access: Primary abstract and reviewed UniProt catalytic-reaction record Functional studies of yeast-expressed human heart muscle carnitine palmitoyltransferase I. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9344464/ · DOI 10.1006/abbi.1997.0314
Complete structured claim and evidence
Purified rat mitochondrial CACT reconstituted into liposomes exchanged carnitine and transported acylcarnitines of several chain lengths.
Rat carnitine-acylcarnitine translocase / Slc25a20 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant rat carrier and proteoliposomes.
limitations
Transport reconstitution is not a human flux measurement.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A separate carrier moves the loaded molecule across the inner membrane.
primary_references
Bacterial overexpression, purification, and reconstitution of the carnitine/acylcarnitine carrier from rat liver mitochondria. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9731180/ · DOI 10.1006/bbrc.1998.9197
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 98–104
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant rat carrier and proteoliposomes. · source_derived_draft · unverified_draft
## l-carnitine-cact-exchange A separate carrier moves the loaded molecule across the inner membrane. Purified rat mitochondrial CACT reconstituted into liposomes exchanged carnitine and transported acylcarnitines of several chain lengths. Model: Recombinant rat carrier and proteoliposomes. Limitations: Transport reconstitution is not a human flux measurement. Evidence access: Primary abstract Bacterial overexpression, purification, and reconstitution of the carnitine/acylcarnitine carrier from rat liver mitochondria. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9731180/ · DOI 10.1006/bbrc.1998.9197
Complete structured claim and evidence
Expressed human CPT2 formed medium- and long-chain acylcarnitines from acyl-CoAs; its physiological matrix-side reaction reconverts incoming acylcarnitines to acyl-CoAs plus free carnitine.
Human carnitine palmitoyltransferase 2 / CPT2 → Palmitoyl-L-carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and reviewed UniProt catalytic-reaction record
experimental_model
Human CPT2 in yeast homogenates; physiological direction from reviewed UniProt P23786/Rhea 12663.
limitations
The experiment directly measured the reverse reaction; direction in a cell depends on compartment and substrates.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The inner enzyme unloads the fatty-acid group and recycles carnitine.
primary_references
Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20538056/ · DOI 10.1016/j.bbadis.2010.06.002
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 106–112
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human CPT2 in yeast homogenates; physiological direction from reviewed UniProt P23786/Rhea 12663. · source_derived_draft · unverified_draft
## l-carnitine-cpt2-return The inner enzyme unloads the fatty-acid group and recycles carnitine. Expressed human CPT2 formed medium- and long-chain acylcarnitines from acyl-CoAs; its physiological matrix-side reaction reconverts incoming acylcarnitines to acyl-CoAs plus free carnitine. Model: Human CPT2 in yeast homogenates; physiological direction from reviewed UniProt P23786/Rhea 12663. Limitations: The experiment directly measured the reverse reaction; direction in a cell depends on compartment and substrates. Evidence access: Primary abstract and reviewed UniProt catalytic-reaction record Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20538056/ · DOI 10.1016/j.bbadis.2010.06.002
Complete structured claim and evidence
Human CPT2 had activity with C8-C18 acyl-CoAs but virtually none with short-chain acyl-CoAs or branched-chain amino-acid oxidation intermediates.
Human carnitine palmitoyltransferase 2 / CPT2 → Propionyl-CoA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human CPT2 substrate panel.
limitations
No claim that every acylcarnitine originates from CPT2.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The long-chain shuttle is not the same enzyme system as short-chain buffering.
primary_references
Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20538056/ · DOI 10.1016/j.bbadis.2010.06.002
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 114–120
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human CPT2 substrate panel. · source_derived_draft · unverified_draft
## l-carnitine-cpt2-specificity The long-chain shuttle is not the same enzyme system as short-chain buffering. Human CPT2 had activity with C8-C18 acyl-CoAs but virtually none with short-chain acyl-CoAs or branched-chain amino-acid oxidation intermediates. Model: Recombinant human CPT2 substrate panel. Limitations: No claim that every acylcarnitine originates from CPT2. Evidence access: Primary abstract Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20538056/ · DOI 10.1016/j.bbadis.2010.06.002
Complete structured claim and evidence
The human SLC25A20 p.Arg133Trp substitution impaired carrier activity after bacterial expression and liposome reconstitution.
Human carnitine-acylcarnitine translocase / SLC25A20 → Human CACT carnitine transport activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Functional variant study within a six-patient CACT-deficiency report.
limitations
CACT deficiency is distinct from OCTN2 deficiency; supplying substrate does not replace a transporter.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A second transport defect can block the mitochondrial shuttle even when carnitine exists.
primary_references
Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcarnitine translocase deficiency. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15365988/ · DOI 10.1002/humu.20085
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 122–128
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Functional variant study within a six-patient CACT-deficiency report. · source_derived_draft · unverified_draft
## l-carnitine-cact-loss A second transport defect can block the mitochondrial shuttle even when carnitine exists. The human SLC25A20 p.Arg133Trp substitution impaired carrier activity after bacterial expression and liposome reconstitution. Model: Functional variant study within a six-patient CACT-deficiency report. Limitations: CACT deficiency is distinct from OCTN2 deficiency; supplying substrate does not replace a transporter. Evidence access: Primary abstract Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcarnitine translocase deficiency. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15365988/ · DOI 10.1002/humu.20085
Complete structured claim and evidence
Myocytes derived from a CPT2-deficient patient accumulated palmitoylcarnitine; incubation at 38 degrees C accentuated accumulation relative to control myocytes.
Human carnitine palmitoyltransferase 2 / CPT2 → Human CPT2-deficient myocyte palmitoylcarnitine accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human patient-derived iPSC myocytes; heat challenge.
limitations
A cellular disease model, not a universal plasma threshold or a supplement trial.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A downstream block can leave more loaded carnitine behind.
primary_references
Functional analysis of iPSC-derived myocytes from a patient with carnitine palmitoyltransferase II deficiency. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24780397/ · DOI 10.1016/j.bbrc.2014.04.084
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 130–136
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human patient-derived iPSC myocytes; heat challenge. · source_derived_draft · unverified_draft
## l-carnitine-cpt2-heat A downstream block can leave more loaded carnitine behind. Myocytes derived from a CPT2-deficient patient accumulated palmitoylcarnitine; incubation at 38 degrees C accentuated accumulation relative to control myocytes. Model: Human patient-derived iPSC myocytes; heat challenge. Limitations: A cellular disease model, not a universal plasma threshold or a supplement trial. Evidence access: Primary abstract Functional analysis of iPSC-derived myocytes from a patient with carnitine palmitoyltransferase II deficiency. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24780397/ · DOI 10.1016/j.bbrc.2014.04.084
Complete structured claim and evidence
Copper inhibited rat-liver CACT carnitine exchange in proteoliposomes, with a native-protein IC50 of 1.6 micromolar.
Copper(II) ion → Rat mitochondrial CACT transport activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Native rat-liver carrier; recombinant cysteine mutants supported involvement of C136 and C155.
limitations
Free copper in an assay is not dietary copper exposure; no clinical deficiency or toxicity threshold follows.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Metal exposure can interfere with the carrier in a controlled assay.
primary_references
Effect of Copper on the Mitochondrial Carnitine/Acylcarnitine Carrier Via Interaction with Cys136 and Cys155. Possible Implications in Pathophysiology. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32070004/ · DOI 10.3390/molecules25040820
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 138–144
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Native rat-liver carrier; recombinant cysteine mutants supported involvement of C136 and C155. · source_derived_draft · unverified_draft
## l-carnitine-copper-carrier Metal exposure can interfere with the carrier in a controlled assay. Copper inhibited rat-liver CACT carnitine exchange in proteoliposomes, with a native-protein IC50 of 1.6 micromolar. Model: Native rat-liver carrier; recombinant cysteine mutants supported involvement of C136 and C155. Limitations: Free copper in an assay is not dietary copper exposure; no clinical deficiency or toxicity threshold follows. Evidence access: Primary abstract Effect of Copper on the Mitochondrial Carnitine/Acylcarnitine Carrier Via Interaction with Cys136 and Cys155. Possible Implications in Pathophysiology. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32070004/ · DOI 10.3390/molecules25040820
Complete structured claim and evidence
Adding reduced glutathione reversed copper inhibition of the reconstituted native rat carnitine-acylcarnitine carrier.
GSH → Rat mitochondrial CACT transport activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat-liver CACT proteoliposome assay.
limitations
Does not demonstrate oral glutathione-carnitine synergy.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The redox environment can change whether the carrier works.
primary_references
Effect of Copper on the Mitochondrial Carnitine/Acylcarnitine Carrier Via Interaction with Cys136 and Cys155. Possible Implications in Pathophysiology. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32070004/ · DOI 10.3390/molecules25040820
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 146–152
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat-liver CACT proteoliposome assay. · source_derived_draft · unverified_draft
## l-carnitine-gsh-carrier The redox environment can change whether the carrier works. Adding reduced glutathione reversed copper inhibition of the reconstituted native rat carnitine-acylcarnitine carrier. Model: Rat-liver CACT proteoliposome assay. Limitations: Does not demonstrate oral glutathione-carnitine synergy. Evidence access: Primary abstract Effect of Copper on the Mitochondrial Carnitine/Acylcarnitine Carrier Via Interaction with Cys136 and Cys155. Possible Implications in Pathophysiology. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32070004/ · DOI 10.3390/molecules25040820
Complete structured claim and evidence
Muscle Crat deletion reduced short-chain acyltransferase activity and acetylcarnitine pools, supporting transfer of acetyl groups from acetyl-CoA to carnitine.
Mouse carnitine acetyltransferase / Crat → Acetyl-L-carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text Figures 1-4
experimental_model
Muscle-specific mouse knockout, enzyme assays and metabolomics.
limitations
Crat buffer function depends on tissue and substrate conditions.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Carnitine can carry excess acetyl groups as well as long fatty-acid groups.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 154–160
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Muscle-specific mouse knockout, enzyme assays and metabolomics. · source_derived_draft · unverified_draft
## l-carnitine-crat-buffer Carnitine can carry excess acetyl groups as well as long fatty-acid groups. Muscle Crat deletion reduced short-chain acyltransferase activity and acetylcarnitine pools, supporting transfer of acetyl groups from acetyl-CoA to carnitine. Model: Muscle-specific mouse knockout, enzyme assays and metabolomics. Limitations: Crat buffer function depends on tissue and substrate conditions. Evidence access: Primary abstract and full-text Figures 1-4 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
Complete structured claim and evidence
Adding carnitine stimulated PDH activity 1.8-fold in control muscle mitochondria but did not stimulate it in Crat-null mitochondria.
L-Carnitine → Mouse muscle mitochondrial pyruvate dehydrogenase activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 4
experimental_model
Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay.
limitations
The effect is context-dependent; liver mitochondria also lacked the stimulation.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Carnitine needs the acetyl-transfer enzyme to relieve this brake on glucose oxidation.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 162–168
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay. · source_derived_draft · unverified_draft
## l-carnitine-crat-pdh Carnitine needs the acetyl-transfer enzyme to relieve this brake on glucose oxidation. Adding carnitine stimulated PDH activity 1.8-fold in control muscle mitochondria but did not stimulate it in Crat-null mitochondria. Model: Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay. Limitations: The effect is context-dependent; liver mitochondria also lacked the stimulation. Evidence access: Primary full-text Figure 4 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
Complete structured claim and evidence
Silencing CRAT in primary human myotubes reduced acetylcarnitine export by 47%.
Human carnitine acetyltransferase / CRAT → Human primary myotube acetylcarnitine export source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 6 and methods
experimental_model
Human myotubes; adenoviral silencing, approximately 60% lower enzyme activity.
limitations
Cell culture, not human supplementation.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
An independent enzyme controls acetyl-group export from muscle cells.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 170–176
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human myotubes; adenoviral silencing, approximately 60% lower enzyme activity. · source_derived_draft · unverified_draft
## l-carnitine-crat-knockdown-export An independent enzyme controls acetyl-group export from muscle cells. Silencing CRAT in primary human myotubes reduced acetylcarnitine export by 47%. Model: Human myotubes; adenoviral silencing, approximately 60% lower enzyme activity. Limitations: Cell culture, not human supplementation. Evidence access: Primary full-text Figure 6 and methods Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
Complete structured claim and evidence
Silencing CRAT in human myotubes reduced glucose uptake by 13% while increasing oleate oxidation.
Human carnitine acetyltransferase / CRAT → Human primary myotube glucose uptake source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 6
experimental_model
Primary human myotube loss-of-function experiment.
limitations
No universal reciprocal rule for all tissues.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
More fat oxidation did not mean better glucose handling in this experiment.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 178–184
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary human myotube loss-of-function experiment. · source_derived_draft · unverified_draft
## l-carnitine-crat-knockdown-glucose More fat oxidation did not mean better glucose handling in this experiment. Silencing CRAT in human myotubes reduced glucose uptake by 13% while increasing oleate oxidation. Model: Primary human myotube loss-of-function experiment. Limitations: No universal reciprocal rule for all tissues. Evidence access: Primary full-text Figure 6 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
Complete structured claim and evidence
Twice-daily carnitine tartrate plus carbohydrate for 24 weeks increased muscle total carnitine by 21%; carbohydrate-only controls did not show loading.
L-Carnitine → Human skeletal-muscle total carnitine content source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Fourteen healthy men; 2 g L-carnitine L-tartrate plus 80 g carbohydrate twice daily.
limitations
Tartrate mass is not pure carnitine mass; the study does not isolate carnitine without carbohydrate.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Human muscle loading depended on the tested intake pattern and time.
primary_references
Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21224234/ · DOI 10.1113/jphysiol.2010.201343
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 186–192
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Fourteen healthy men; 2 g L-carnitine L-tartrate plus 80 g carbohydrate twice daily. · source_derived_draft · unverified_draft
## l-carnitine-muscle-loading Human muscle loading depended on the tested intake pattern and time. Twice-daily carnitine tartrate plus carbohydrate for 24 weeks increased muscle total carnitine by 21%; carbohydrate-only controls did not show loading. Model: Fourteen healthy men; 2 g L-carnitine L-tartrate plus 80 g carbohydrate twice daily. Limitations: Tartrate mass is not pure carnitine mass; the study does not isolate carnitine without carbohydrate. Evidence access: Primary abstract Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21224234/ · DOI 10.1113/jphysiol.2010.201343
Complete structured claim and evidence
After the loading regimen, muscle glycogen use at 50% exercise intensity was 55% lower than in carbohydrate-only controls.
L-Carnitine → Human exercise muscle glycogen utilization source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same 24-week trial; muscle biopsies during cycling.
limitations
Glycogen sparing is compatible with more fat use, but is not proof of body-fat loss.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The fuel effect changed with exercise demand.
primary_references
Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21224234/ · DOI 10.1113/jphysiol.2010.201343
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 194–200
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same 24-week trial; muscle biopsies during cycling. · source_derived_draft · unverified_draft
## l-carnitine-low-work-glycogen The fuel effect changed with exercise demand. After the loading regimen, muscle glycogen use at 50% exercise intensity was 55% lower than in carbohydrate-only controls. Model: Same 24-week trial; muscle biopsies during cycling. Limitations: Glycogen sparing is compatible with more fat use, but is not proof of body-fat loss. Evidence access: Primary abstract Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21224234/ · DOI 10.1113/jphysiol.2010.201343
Complete structured claim and evidence
At 80% exercise intensity after loading, muscle PDC activation was 38% higher and lactate was lower than in controls.
L-Carnitine → Human exercise muscle pyruvate dehydrogenase complex activation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same human trial, higher-intensity exercise phase.
limitations
Different workload explains the different direction; this is not a contradiction.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
At higher demand, the same intervention supported glucose oxidation.
primary_references
Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21224234/ · DOI 10.1113/jphysiol.2010.201343
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 202–208
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same human trial, higher-intensity exercise phase. · source_derived_draft · unverified_draft
## l-carnitine-high-work-pdc At higher demand, the same intervention supported glucose oxidation. At 80% exercise intensity after loading, muscle PDC activation was 38% higher and lactate was lower than in controls. Model: Same human trial, higher-intensity exercise phase. Limitations: Different workload explains the different direction; this is not a contradiction. Evidence access: Primary abstract Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21224234/ · DOI 10.1113/jphysiol.2010.201343
Complete structured claim and evidence
Isotope-labeled acetylcarnitine supplied acetyl-CoA and fatty-acid carbon in glucose-limited human U87MG glioma cells.
Acetyl-L-carnitine → Human U87MG acetyl-CoA labeling from acetylcarnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human U87MG culture, isotope tracing.
limitations
Does not show that oral acetylcarnitine causes or treats cancer.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The acetylated form can deliver carbon for cellular synthesis.
primary_references
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 210–216
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human U87MG culture, isotope tracing. · source_derived_draft · unverified_draft
## l-carnitine-acetyl-carbon The acetylated form can deliver carbon for cellular synthesis. Isotope-labeled acetylcarnitine supplied acetyl-CoA and fatty-acid carbon in glucose-limited human U87MG glioma cells. Model: Human U87MG culture, isotope tracing. Limitations: Does not show that oral acetylcarnitine causes or treats cancer. Evidence access: Primary abstract Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
Complete structured claim and evidence
Deleting CROT reduced labeling of acetyl-CoA and palmitate from exogenous acetylcarnitine; CROT cDNA rescue restored acetyl-CoA labeling.
Human carnitine octanoyltransferase / CROT → Human U87MG acetyl-CoA labeling from acetylcarnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 5 and enzyme assays
experimental_model
Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation.
limitations
Compartment and substrate supply may explain why this enzyme dominates in these cells.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Another carnitine enzyme provided this carbon route.
primary_references
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 218–224
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation. · source_derived_draft · unverified_draft
## l-carnitine-crot-knockout Another carnitine enzyme provided this carbon route. Deleting CROT reduced labeling of acetyl-CoA and palmitate from exogenous acetylcarnitine; CROT cDNA rescue restored acetyl-CoA labeling. Model: Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation. Limitations: Compartment and substrate supply may explain why this enzyme dominates in these cells. Evidence access: Primary full-text Figure 5 and enzyme assays Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
Complete structured claim and evidence
Deleting CRAT did not diminish acetyl-CoA labeling from supplied acetylcarnitine in U87MG cells.
Human carnitine acetyltransferase / CRAT → Human U87MG acetyl-CoA labeling from acetylcarnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 4
experimental_model
Human U87MG knockout and tracer experiment.
limitations
Incoming acetylcarnitine utilization differs from mitochondrial production; not a conflict with muscle export.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The enzyme needed to make acetylcarnitine need not be the one that uses it.
primary_references
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 226–232
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human U87MG knockout and tracer experiment. · source_derived_draft · unverified_draft
## l-carnitine-crat-null-assimilation The enzyme needed to make acetylcarnitine need not be the one that uses it. Deleting CRAT did not diminish acetyl-CoA labeling from supplied acetylcarnitine in U87MG cells. Model: Human U87MG knockout and tracer experiment. Limitations: Incoming acetylcarnitine utilization differs from mitochondrial production; not a conflict with muscle export. Evidence access: Primary full-text Figure 4 Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
Complete structured claim and evidence
Adding acetylcarnitine increased histone acetylation in lipid-depleted mouse HCC cells lacking both ACLY and ACSS2.
Acetyl-L-carnitine → Mouse HCC-cell histone acetylation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 6 and cell-line methods
experimental_model
Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing.
limitations
An engineered cancer-cell bypass is not a general epigenetic benefit.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Acetyl-group transport can connect energy metabolism to chromatin chemistry.
primary_references
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 234–240
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing. · source_derived_draft · unverified_draft
## l-carnitine-histone-carbon Acetyl-group transport can connect energy metabolism to chromatin chemistry. Adding acetylcarnitine increased histone acetylation in lipid-depleted mouse HCC cells lacking both ACLY and ACSS2. Model: Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing. Limitations: An engineered cancer-cell bypass is not a general epigenetic benefit. Evidence access: Primary full-text Figure 6 and cell-line methods Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115
Complete structured claim and evidence
Removing Crat impaired glucose-derived lipid synthesis in ACLY-deficient mouse HCC cells.
Mouse carnitine acetyltransferase / Crat → Mouse HCC-cell glucose-derived lipid synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text and cell-line methods
experimental_model
Mouse HCC cell genetic perturbation and carbon tracing.
limitations
Dependence arises in the specified metabolic background.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The acetyl shuttle can supply lipid synthesis when a usual route is missing.
primary_references
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 242–248
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse HCC cell genetic perturbation and carbon tracing. · source_derived_draft · unverified_draft
## l-carnitine-crat-lipogenesis The acetyl shuttle can supply lipid synthesis when a usual route is missing. Removing Crat impaired glucose-derived lipid synthesis in ACLY-deficient mouse HCC cells. Model: Mouse HCC cell genetic perturbation and carbon tracing. Limitations: Dependence arises in the specified metabolic background. Evidence access: Primary full text and cell-line methods Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115
Complete structured claim and evidence
Giving L-carnitine to three patients with propionic acidemia increased urinary propionylcarnitine, verified by mass spectrometry.
L-Carnitine → Human urinary propionylcarnitine excretion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine.
limitations
Restoration of mitochondrial free CoA was a proposed mechanism, not directly measured.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Acyl-group disposal can consume and export carnitine.
primary_references
L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6725560/ · DOI 10.1172/JCI111387
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 250–256
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine. · source_derived_draft · unverified_draft
## l-carnitine-organic-acid-export Acyl-group disposal can consume and export carnitine. Giving L-carnitine to three patients with propionic acidemia increased urinary propionylcarnitine, verified by mass spectrometry. Model: Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine. Limitations: Restoration of mitochondrial free CoA was a proposed mechanism, not directly measured. Evidence access: Primary abstract L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6725560/ · DOI 10.1172/JCI111387
Complete structured claim and evidence
Four patients with propionic or methylmalonic aciduria had low plasma free carnitine and elevated short-chain acylcarnitine excretion; muscle carnitine was low in two biopsied patients.
Propionylcarnitine → Human free carnitine pools in organic acidemias source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Two PA and two MMA cases; plasma, urine and selected muscle measurements.
limitations
Export-driven tissue depletion is the authors' mechanism; these inherited conditions are not synonymous with dietary B12 deficiency.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A metabolic block can tie up carnitine and lead to its loss in urine.
primary_references
Propionylcarnitine excretion in propionic and methylmalonic acidurias: a cause of carnitine deficiency. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6723070/ · DOI 10.1016/0009-8981(84)90187-6
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 258–264
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Two PA and two MMA cases; plasma, urine and selected muscle measurements. · source_derived_draft · unverified_draft
## l-carnitine-organic-acid-loss A metabolic block can tie up carnitine and lead to its loss in urine. Four patients with propionic or methylmalonic aciduria had low plasma free carnitine and elevated short-chain acylcarnitine excretion; muscle carnitine was low in two biopsied patients. Model: Two PA and two MMA cases; plasma, urine and selected muscle measurements. Limitations: Export-driven tissue depletion is the authors' mechanism; these inherited conditions are not synonymous with dietary B12 deficiency. Evidence access: Primary abstract Propionylcarnitine excretion in propionic and methylmalonic acidurias: a cause of carnitine deficiency. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6723070/ · DOI 10.1016/0009-8981(84)90187-6
Complete structured claim and evidence
Twelve days of pivmecillinam reduced mean serum free carnitine from 42.8 to 11.6 micromolar, while measured muscle carnitine was unchanged.
Pivmecillinam → Human serum L-carnitine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Six healthy men; 1200 mg/day.
limitations
A small provocation study, not a universal drug effect size.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A drug-associated shortfall can differ between blood and muscle.
primary_references
Impaired ketogenesis in carnitine depletion caused by short-term administration of pivalic acid prodrug. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7917463/ · DOI 10.1006/bmmb.1994.1028
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 266–272
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six healthy men; 1200 mg/day. · source_derived_draft · unverified_draft
## l-carnitine-pivalate-depletion A drug-associated shortfall can differ between blood and muscle. Twelve days of pivmecillinam reduced mean serum free carnitine from 42.8 to 11.6 micromolar, while measured muscle carnitine was unchanged. Model: Six healthy men; 1200 mg/day. Limitations: A small provocation study, not a universal drug effect size. Evidence access: Primary abstract Impaired ketogenesis in carnitine depletion caused by short-term administration of pivalic acid prodrug. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7917463/ · DOI 10.1006/bmmb.1994.1028
Complete structured claim and evidence
After pivmecillinam-associated carnitine depletion, two of six subjects showed impaired ketone production during a 36-hour fast.
Pivmecillinam → Human fasting ketone production after pivmecillinam source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human before-and-after fasting challenge.
limitations
Only a subset was affected; no universal plasma cutoff or dietary diagnosis was established.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Low carnitine can limit the switch to fat-derived fasting fuel.
primary_references
Impaired ketogenesis in carnitine depletion caused by short-term administration of pivalic acid prodrug. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7917463/ · DOI 10.1006/bmmb.1994.1028
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 274–280
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human before-and-after fasting challenge. · source_derived_draft · unverified_draft
## l-carnitine-pivalate-ketones Low carnitine can limit the switch to fat-derived fasting fuel. After pivmecillinam-associated carnitine depletion, two of six subjects showed impaired ketone production during a 36-hour fast. Model: Human before-and-after fasting challenge. Limitations: Only a subset was affected; no universal plasma cutoff or dietary diagnosis was established. Evidence access: Primary abstract Impaired ketogenesis in carnitine depletion caused by short-term administration of pivalic acid prodrug. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7917463/ · DOI 10.1006/bmmb.1994.1028
Complete structured claim and evidence
In the patient observed when starting valproate, plasma carnitine fell during weeks 1-3 and recovered by weeks 3-5.
Valproate → Human plasma carnitine during valproate therapy source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
One longitudinal initiation case plus ten long-term patients.
limitations
Suppressed synthesis and increased OCTN2 expression were proposed explanations, not directly measured human mechanisms.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Drug-associated carnitine changes can evolve over time.
primary_references
Effect of short- and long-term treatment with valproate on carnitine homeostasis in humans. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22743351/ · DOI 10.1097/FTD.0b013e3182608e2f
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 282–288
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · One longitudinal initiation case plus ten long-term patients. · source_derived_draft · unverified_draft
## l-carnitine-valproate-timecourse Drug-associated carnitine changes can evolve over time. In the patient observed when starting valproate, plasma carnitine fell during weeks 1-3 and recovered by weeks 3-5. Model: One longitudinal initiation case plus ten long-term patients. Limitations: Suppressed synthesis and increased OCTN2 expression were proposed explanations, not directly measured human mechanisms. Evidence access: Primary abstract Effect of short- and long-term treatment with valproate on carnitine homeostasis in humans. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22743351/ · DOI 10.1097/FTD.0b013e3182608e2f
Complete structured claim and evidence
Valproylcarnitine fractional renal excretion approached 100%, unlike the strongly reabsorbed free carnitine pool; transporter assays showed low OCTN2 affinity.
Valproyl-L-carnitine → Human renal fractional excretion of valproylcarnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human urine/plasma measurements and OCTN2 assays.
limitations
The authors found that excreted valproylcarnitine did not impair renal handling of free carnitine in vivo.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The drug-linked ester is handled differently from free carnitine.
primary_references
Effect of short- and long-term treatment with valproate on carnitine homeostasis in humans. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22743351/ · DOI 10.1097/FTD.0b013e3182608e2f
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 290–296
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human urine/plasma measurements and OCTN2 assays. · source_derived_draft · unverified_draft
## l-carnitine-valproate-clearance The drug-linked ester is handled differently from free carnitine. Valproylcarnitine fractional renal excretion approached 100%, unlike the strongly reabsorbed free carnitine pool; transporter assays showed low OCTN2 affinity. Model: Human urine/plasma measurements and OCTN2 assays. Limitations: The authors found that excreted valproylcarnitine did not impair renal handling of free carnitine in vivo. Evidence access: Primary abstract Effect of short- and long-term treatment with valproate on carnitine homeostasis in humans. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22743351/ · DOI 10.1097/FTD.0b013e3182608e2f
Complete structured claim and evidence
Adding 10 mM carnitine reduced nuclear T3 uptake in human HepG2 cells by about 35%; 50 mM produced a larger reduction.
L-Carnitine → Human HepG2 nuclear T3 uptake source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human HepG2 uptake assay; high millimolar exposures.
limitations
No direct inhibition of T3 binding to isolated nuclei was observed; not proof of iodine depletion or routine-dose hypothyroidism.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Carnitine can affect thyroid-hormone access to the nucleus in cell experiments.
primary_references
Carnitine is a naturally occurring inhibitor of thyroid hormone nuclear uptake. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11201848/ · DOI 10.1089/thy.2000.10.1043
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 298–304
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HepG2 uptake assay; high millimolar exposures. · source_derived_draft · unverified_draft
## l-carnitine-thyroid-nuclear Carnitine can affect thyroid-hormone access to the nucleus in cell experiments. Adding 10 mM carnitine reduced nuclear T3 uptake in human HepG2 cells by about 35%; 50 mM produced a larger reduction. Model: Human HepG2 uptake assay; high millimolar exposures. Limitations: No direct inhibition of T3 binding to isolated nuclei was observed; not proof of iodine depletion or routine-dose hypothyroidism. Evidence access: Primary abstract Carnitine is a naturally occurring inhibitor of thyroid hormone nuclear uptake. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11201848/ · DOI 10.1089/thy.2000.10.1043
Complete structured claim and evidence
In a six-month trial of 50 women on fixed TSH-suppressive thyroxine, 2 or 4 g/day carnitine reduced or limited several hyperthyroid symptoms during treatment periods.
L-Carnitine → Human thyroxine-induced hyperthyroid symptoms source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Five groups of ten; randomized, double-blind placebo-controlled treatment periods.
limitations
Specific iatrogenic hyperthyroidism context; does not justify changing thyroid medication or establish universal safety.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A small clinical trial tested peripheral thyroid-hormone effects.
primary_references
Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11502782/ · DOI 10.1210/jcem.86.8.7747
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 306–312
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Five groups of ten; randomized, double-blind placebo-controlled treatment periods. · source_derived_draft · unverified_draft
## l-carnitine-thyroid-clinical A small clinical trial tested peripheral thyroid-hormone effects. In a six-month trial of 50 women on fixed TSH-suppressive thyroxine, 2 or 4 g/day carnitine reduced or limited several hyperthyroid symptoms during treatment periods. Model: Five groups of ten; randomized, double-blind placebo-controlled treatment periods. Limitations: Specific iatrogenic hyperthyroidism context; does not justify changing thyroid medication or establish universal safety. Evidence access: Primary abstract Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11502782/ · DOI 10.1210/jcem.86.8.7747
Complete structured claim and evidence
Acetyl-L-carnitine treatment increased Grm2-associated H3K27 acetylation and mGlu2 expression in Flinders Sensitive Line rats.
Acetyl-L-carnitine → Rat hippocampal and prefrontal Grm2-associated acetylation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat depression-model hippocampus and prefrontal cortex.
limitations
Histone acetylation differs from DNA methylation; this is not proof of human antidepressant efficacy.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The acetylated form altered a glutamate-signaling pathway in a rodent model.
primary_references
L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23382250/ · DOI 10.1073/pnas.1216100110
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 314–320
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat depression-model hippocampus and prefrontal cortex. · source_derived_draft · unverified_draft
## l-carnitine-brain-acetylation The acetylated form altered a glutamate-signaling pathway in a rodent model. Acetyl-L-carnitine treatment increased Grm2-associated H3K27 acetylation and mGlu2 expression in Flinders Sensitive Line rats. Model: Rat depression-model hippocampus and prefrontal cortex. Limitations: Histone acetylation differs from DNA methylation; this is not proof of human antidepressant efficacy. Evidence access: Primary abstract L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23382250/ · DOI 10.1073/pnas.1216100110
Complete structured claim and evidence
Acetyl-L-carnitine did not produce the reported behavioral benefit in mGlu2-knockout mice exposed to chronic unpredictable stress.
Mouse metabotropic glutamate receptor 2 / Grm2 → Mouse stress-model behavioral response to acetylcarnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse knockout and stress-behavior experiments.
limitations
Behavioral tests are not human depression outcomes.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Removing the receptor tested whether the rodent effect depended on it.
primary_references
L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23382250/ · DOI 10.1073/pnas.1216100110
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 322–328
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout and stress-behavior experiments. · source_derived_draft · unverified_draft
## l-carnitine-brain-receptor-required Removing the receptor tested whether the rodent effect depended on it. Acetyl-L-carnitine did not produce the reported behavioral benefit in mGlu2-knockout mice exposed to chronic unpredictable stress. Model: Mouse knockout and stress-behavior experiments. Limitations: Behavioral tests are not human depression outcomes. Evidence access: Primary abstract L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23382250/ · DOI 10.1073/pnas.1216100110
Complete structured claim and evidence
In a 409-patient randomized trial during adjuvant taxane chemotherapy, acetyl-L-carnitine did not significantly improve the primary 12-week neuropathy endpoint.
Acetyl-L-carnitine → Human taxane-associated peripheral neuropathy severity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Women with breast cancer; 3 g/day acetyl-L-carnitine versus placebo.
limitations
A finding for this derivative and treatment context, not every carnitine use.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A plausible nerve-protection idea failed its main clinical test.
primary_references
Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23733756/ · DOI 10.1200/JCO.2012.44.8738
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 330–336
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Women with breast cancer; 3 g/day acetyl-L-carnitine versus placebo. · source_derived_draft · unverified_draft
## l-carnitine-alc-neuropathy-null A plausible nerve-protection idea failed its main clinical test. In a 409-patient randomized trial during adjuvant taxane chemotherapy, acetyl-L-carnitine did not significantly improve the primary 12-week neuropathy endpoint. Model: Women with breast cancer; 3 g/day acetyl-L-carnitine versus placebo. Limitations: A finding for this derivative and treatment context, not every carnitine use. Evidence access: Primary abstract Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23733756/ · DOI 10.1200/JCO.2012.44.8738
Complete structured claim and evidence
At 24 weeks in the same taxane trial, the acetyl-L-carnitine arm had worse neuropathy scores and more severe neurotoxicity than placebo.
Acetyl-L-carnitine → Human taxane-associated peripheral neuropathy severity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same randomized trial; prespecified secondary follow-up.
limitations
Not a demonstrated molecular explanation of the harm; keep the clinical outcome visible.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Longer follow-up revealed harm in that setting.
primary_references
Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23733756/ · DOI 10.1200/JCO.2012.44.8738
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 338–344
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same randomized trial; prespecified secondary follow-up. · source_derived_draft · unverified_draft
## l-carnitine-alc-neuropathy-harm Longer follow-up revealed harm in that setting. At 24 weeks in the same taxane trial, the acetyl-L-carnitine arm had worse neuropathy scores and more severe neurotoxicity than placebo. Model: Same randomized trial; prespecified secondary follow-up. Limitations: Not a demonstrated molecular explanation of the harm; keep the clinical outcome visible. Evidence access: Primary abstract Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23733756/ · DOI 10.1200/JCO.2012.44.8738
Complete structured claim and evidence
Human tracer, fecal culture and antibiotic studies supported microbial conversion of carnitine to gamma-butyrobetaine, occurring rapidly in both dietary groups.
L-Carnitine → gamma-Butyrobetaine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Omnivores and vegans/vegetarians; labeled oral substrates, cultures and antibiotics.
limitations
This host-microbe direction differs from human BBOX1 synthesis of carnitine; no single universal flux.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Gut microbes can send carnitine into a different chemical pathway.
primary_references
l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30530985/ · DOI 10.1172/JCI94601
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 346–352
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Omnivores and vegans/vegetarians; labeled oral substrates, cultures and antibiotics. · source_derived_draft · unverified_draft
## l-carnitine-microbial-first-step Gut microbes can send carnitine into a different chemical pathway. Human tracer, fecal culture and antibiotic studies supported microbial conversion of carnitine to gamma-butyrobetaine, occurring rapidly in both dietary groups. Model: Omnivores and vegans/vegetarians; labeled oral substrates, cultures and antibiotics. Limitations: This host-microbe direction differs from human BBOX1 synthesis of carnitine; no single universal flux. Evidence access: Primary abstract l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30530985/ · DOI 10.1172/JCI94601
Complete structured claim and evidence
Chronic carnitine exposure increased microbial gamma-butyrobetaine-to-TMA conversion; baseline labeled TMAO generation was greater in omnivores.
L-Carnitine → Human gut microbial gamma-butyrobetaine-to-TMA conversion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human isotope challenges before/after at least two months of supplementation.
limitations
A metabolite-production study does not prove cardiovascular events from a given supplement dose.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The response depends partly on microbial adaptation and diet.
primary_references
l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30530985/ · DOI 10.1172/JCI94601
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 354–360
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human isotope challenges before/after at least two months of supplementation. · source_derived_draft · unverified_draft
## l-carnitine-microbial-induction The response depends partly on microbial adaptation and diet. Chronic carnitine exposure increased microbial gamma-butyrobetaine-to-TMA conversion; baseline labeled TMAO generation was greater in omnivores. Model: Human isotope challenges before/after at least two months of supplementation. Limitations: A metabolite-production study does not prove cardiovascular events from a given supplement dose. Evidence access: Primary abstract l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30530985/ · DOI 10.1172/JCI94601
Complete structured claim and evidence
Adding E. timonensis in coculture completed the carnitine-to-TMA conversion using other microbes' gamma-butyrobetaine production.
Emergencia timonensis → Human gut microbial gamma-butyrobetaine-to-TMA conversion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cultured human fecal commensals under anaerobic conditions.
limitations
Community capability does not establish the abundance or activity in every person.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Different microbes can carry out consecutive steps.
primary_references
l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30530985/ · DOI 10.1172/JCI94601
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 362–368
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cultured human fecal commensals under anaerobic conditions. · source_derived_draft · unverified_draft
## l-carnitine-microbial-coculture Different microbes can carry out consecutive steps. Adding E. timonensis in coculture completed the carnitine-to-TMA conversion using other microbes' gamma-butyrobetaine production. Model: Cultured human fecal commensals under anaerobic conditions. Limitations: Community capability does not establish the abundance or activity in every person. Evidence access: Primary abstract l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30530985/ · DOI 10.1172/JCI94601
Complete structured claim and evidence
Purified BbuB and BbuC together transferred CoA onto gamma-butyrobetaine; neither component alone reproduced the tested activity.
Emergencia timonensis BbuB CoA-transferase component → Gamma-butyrobetainyl-CoA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 3 and enzyme experiments
experimental_model
E. timonensis enzymes; recombinant expression and reconstitution.
limitations
Acetyl-CoA was preferred among tested donors; in vivo donor use can differ.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The microbial route first activates its substrate with CoA.
primary_references
Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34362844/ · DOI 10.1073/pnas.2101498118
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 370–376
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · E. timonensis enzymes; recombinant expression and reconstitution. · source_derived_draft · unverified_draft
## l-carnitine-bbu-coa The microbial route first activates its substrate with CoA. Purified BbuB and BbuC together transferred CoA onto gamma-butyrobetaine; neither component alone reproduced the tested activity. Model: E. timonensis enzymes; recombinant expression and reconstitution. Limitations: Acetyl-CoA was preferred among tested donors; in vivo donor use can differ. Evidence access: Primary full-text Figure 3 and enzyme experiments Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34362844/ · DOI 10.1073/pnas.2101498118
Complete structured claim and evidence
BbuA converted gamma-butyrobetainyl-CoA to TMA and crotonyl-CoA in the reconstituted anaerobic pathway.
Emergencia timonensis BbuA / GbuA TMA-generating enzyme → Gamma-butyrobetainyl-CoA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text and pathway reconstitution
experimental_model
E. timonensis BbuA biochemical characterization.
limitations
Flavin participation is supported; detailed catalytic chemistry remained proposed in this paper.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A microbial enzyme releases the trimethylamine group.
primary_references
Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34362844/ · DOI 10.1073/pnas.2101498118
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 378–384
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · E. timonensis BbuA biochemical characterization. · source_derived_draft · unverified_draft
## l-carnitine-bbua-lyase A microbial enzyme releases the trimethylamine group. BbuA converted gamma-butyrobetainyl-CoA to TMA and crotonyl-CoA in the reconstituted anaerobic pathway. Model: E. timonensis BbuA biochemical characterization. Limitations: Flavin participation is supported; detailed catalytic chemistry remained proposed in this paper. Evidence access: Primary full text and pathway reconstitution Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34362844/ · DOI 10.1073/pnas.2101498118
Complete structured claim and evidence
Acinetobacter baumannii CntA/CntB catalyzed oxygen-dependent carnitine cleavage to TMA and malic semialdehyde.
Acinetobacter baumannii CntA carnitine monooxygenase component → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified bacterial enzyme complex, spectroscopy and mutagenesis.
limitations
This aerobic chemistry is not assumed to dominate the anoxic colon.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A separate microbial route needs oxygen.
primary_references
Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32694223/ · DOI 10.1074/jbc.RA120.014266
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 386–392
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial enzyme complex, spectroscopy and mutagenesis. · source_derived_draft · unverified_draft
## l-carnitine-cnta-cleavage A separate microbial route needs oxygen. Acinetobacter baumannii CntA/CntB catalyzed oxygen-dependent carnitine cleavage to TMA and malic semialdehyde. Model: Purified bacterial enzyme complex, spectroscopy and mutagenesis. Limitations: This aerobic chemistry is not assumed to dominate the anoxic colon. Evidence access: Primary abstract Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32694223/ · DOI 10.1074/jbc.RA120.014266
Complete structured claim and evidence
CntB passed NADH-derived electrons through FMN and iron-sulfur centers to support CntA oxygen activation.
Acinetobacter baumannii CntB reductase component → Acinetobacter baumannii CntA carnitine monooxygenase component source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Acinetobacter enzyme redox spectroscopy and site-directed mutants.
limitations
Bacterial cofactor dependence does not show that human B2 or iron supplementation increases TMAO.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Riboflavin-derived FMN, iron centers and NADH connect to microbial carnitine chemistry.
primary_references
Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32694223/ · DOI 10.1074/jbc.RA120.014266
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 394–400
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Acinetobacter enzyme redox spectroscopy and site-directed mutants. · source_derived_draft · unverified_draft
## l-carnitine-cntb-redox Riboflavin-derived FMN, iron centers and NADH connect to microbial carnitine chemistry. CntB passed NADH-derived electrons through FMN and iron-sulfur centers to support CntA oxygen activation. Model: Acinetobacter enzyme redox spectroscopy and site-directed mutants. Limitations: Bacterial cofactor dependence does not show that human B2 or iron supplementation increases TMAO. Evidence access: Primary abstract Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32694223/ · DOI 10.1074/jbc.RA120.014266
Complete structured claim and evidence
Adding E. timonensis to defined microbial communities in gnotobiotic mice completed carnitine-to-TMA conversion, raised TMAO and enhanced thrombosis after arterial injury.
Emergencia timonensis → Gnotobiotic mouse arterial-injury thrombosis potential source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Gnotobiotic mouse transplantation with defined communities.
limitations
Not a human clinical-event trial.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A microbial addition tested a downstream vascular consequence.
primary_references
The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34949826/ · DOI 10.1038/s41564-021-01010-x
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 402–408
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Gnotobiotic mouse transplantation with defined communities. · source_derived_draft · unverified_draft
## l-carnitine-mouse-microbial-thrombosis A microbial addition tested a downstream vascular consequence. Adding E. timonensis to defined microbial communities in gnotobiotic mice completed carnitine-to-TMA conversion, raised TMAO and enhanced thrombosis after arterial injury. Model: Gnotobiotic mouse transplantation with defined communities. Limitations: Not a human clinical-event trial. Evidence access: Primary abstract The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34949826/ · DOI 10.1038/s41564-021-01010-x
Complete structured claim and evidence
Chronic dietary carnitine increased atherosclerosis in the studied mice; concurrent microbial suppression prevented that increase.
L-Carnitine → Mouse atherosclerotic lesions during carnitine exposure, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Atherosclerosis-prone mice; dietary intervention with microbiota suppression comparison.
limitations
Human cohort associations in the same paper are not randomized supplement effects.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
One mouse study linked carnitine metabolism to more arterial lesions.
primary_references
Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23563705/ · DOI 10.1038/nm.3145
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 410–416
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Atherosclerosis-prone mice; dietary intervention with microbiota suppression comparison. · source_derived_draft · unverified_draft
## l-carnitine-mouse-atheroma-increase One mouse study linked carnitine metabolism to more arterial lesions. Chronic dietary carnitine increased atherosclerosis in the studied mice; concurrent microbial suppression prevented that increase. Model: Atherosclerosis-prone mice; dietary intervention with microbiota suppression comparison. Limitations: Human cohort associations in the same paper are not randomized supplement effects. Evidence access: Primary abstract Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23563705/ · DOI 10.1038/nm.3145
Complete structured claim and evidence
In male ApoE-null mice expressing human CETP, carnitine raised TMAO but higher TMAO correlated with smaller aortic lesions across treatment groups.
Trimethylamine N-oxide / TMAO → Mouse atherosclerotic lesions during carnitine exposure, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Twelve-week carnitine and/or methimazole study; hCETP-expressing ApoE-null mice.
limitations
The inverse correlation does not establish TMAO protection; genotype, sex and co-treatment differ.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Another mouse model did not show the same adverse relationship.
primary_references
L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(-/-) transgenic mice expressing CETP. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26584136/ · DOI 10.1016/j.atherosclerosis.2015.10.108
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 418–424
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Twelve-week carnitine and/or methimazole study; hCETP-expressing ApoE-null mice. · source_derived_draft · unverified_draft
## l-carnitine-mouse-atheroma-inverse Another mouse model did not show the same adverse relationship. In male ApoE-null mice expressing human CETP, carnitine raised TMAO but higher TMAO correlated with smaller aortic lesions across treatment groups. Model: Twelve-week carnitine and/or methimazole study; hCETP-expressing ApoE-null mice. Limitations: The inverse correlation does not establish TMAO protection; genotype, sex and co-treatment differ. Evidence access: Primary abstract L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(-/-) transgenic mice expressing CETP. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26584136/ · DOI 10.1016/j.atherosclerosis.2015.10.108
Complete structured claim and evidence
Two grams/day carnitine for six months did not significantly change the primary total-carotid-plaque-volume outcome versus placebo.
L-Carnitine → Human carotid total plaque volume source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
157 participants with metabolic syndrome and pre-existing plaque; randomized trial.
limitations
A six-month imaging endpoint is not a lifetime clinical-event result.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The human trial did not show a plaque-volume benefit or increase.
primary_references
Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35366920/ · DOI 10.1186/s12986-022-00661-9
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 426–432
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · 157 participants with metabolic syndrome and pre-existing plaque; randomized trial. · source_derived_draft · unverified_draft
## l-carnitine-human-plaque-null The human trial did not show a plaque-volume benefit or increase. Two grams/day carnitine for six months did not significantly change the primary total-carotid-plaque-volume outcome versus placebo. Model: 157 participants with metabolic syndrome and pre-existing plaque; randomized trial. Limitations: A six-month imaging endpoint is not a lifetime clinical-event result. Evidence access: Primary abstract Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35366920/ · DOI 10.1186/s12986-022-00661-9
Complete structured claim and evidence
The carnitine arm in the same trial had greater progression of carotid stenosis than placebo, reported as a 9.3% difference; total and LDL cholesterol also increased.
L-Carnitine → Human carotid atherosclerotic stenosis source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same 157-participant randomized trial; secondary endpoints.
limitations
Different endpoints are not a contradiction; the study does not isolate TMAO as the mediator.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A different vascular endpoint showed a concerning signal.
primary_references
Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35366920/ · DOI 10.1186/s12986-022-00661-9
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 434–440
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same 157-participant randomized trial; secondary endpoints. · source_derived_draft · unverified_draft
## l-carnitine-human-stenosis A different vascular endpoint showed a concerning signal. The carnitine arm in the same trial had greater progression of carotid stenosis than placebo, reported as a 9.3% difference; total and LDL cholesterol also increased. Model: Same 157-participant randomized trial; secondary endpoints. Limitations: Different endpoints are not a contradiction; the study does not isolate TMAO as the mediator. Evidence access: Primary abstract Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35366920/ · DOI 10.1186/s12986-022-00661-9
Complete structured claim and evidence
Genetic loss of Cpt1a or Cpt2 did not reproduce the strong block of IL-4-driven macrophage polarization caused by high-dose etomoxir.
Mouse carnitine palmitoyltransferase 2 / Cpt2 → Mouse macrophage IL-4-induced polarization source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text mouse macrophage methods
experimental_model
Mouse macrophage genetic and pharmacologic comparisons.
limitations
Context-specific immune result, not a statement that fatty-acid oxidation never matters.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A drug effect did not prove that the carnitine shuttle was required.
primary_references
Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 442–448
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophage genetic and pharmacologic comparisons. · source_derived_draft · unverified_draft
## l-carnitine-macrophage-cpt-loss A drug effect did not prove that the carnitine shuttle was required. Genetic loss of Cpt1a or Cpt2 did not reproduce the strong block of IL-4-driven macrophage polarization caused by high-dose etomoxir. Model: Mouse macrophage genetic and pharmacologic comparisons. Limitations: Context-specific immune result, not a statement that fatty-acid oxidation never matters. Evidence access: Primary abstract and full-text mouse macrophage methods Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001
Complete structured claim and evidence
High etomoxir exposure depleted free CoA and inhibited IL-4 macrophage polarization even without Cpt1a or Cpt2 expression.
Etomoxir → Mouse macrophage free CoA pool source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text genetic/pharmacologic experiments
experimental_model
Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1.
limitations
Etomoxiryl-CoA formation was the proposed depletion mechanism; not evidence that carnitine depletes CoA.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The experiment exposed a CoA-related off-target effect.
primary_references
Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 450–456
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1. · source_derived_draft · unverified_draft
## l-carnitine-etomoxir-coa The experiment exposed a CoA-related off-target effect. High etomoxir exposure depleted free CoA and inhibited IL-4 macrophage polarization even without Cpt1a or Cpt2 expression. Model: Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1. Limitations: Etomoxiryl-CoA formation was the proposed depletion mechanism; not evidence that carnitine depletes CoA. Evidence access: Primary abstract and full-text genetic/pharmacologic experiments Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001
Complete structured claim and evidence
T-cell-specific Cpt1a deletion showed that the ACC2/Cpt1a pathway was largely dispensable for memory and regulatory T-cell formation in the tested models.
Mouse carnitine palmitoyltransferase 1A / Cpt1a → Mouse memory and regulatory T-cell formation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text mouse genetic methods
experimental_model
Mouse T-cell conditional knockout and differentiation/infection experiments.
limitations
Does not exclude other tissue or immune contexts.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Genetic tests limit broad claims about carnitine-shuttle dependence of immunity.
primary_references
Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043753/ · DOI 10.1016/j.cmet.2018.06.002
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 458–464
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse T-cell conditional knockout and differentiation/infection experiments. · source_derived_draft · unverified_draft
## l-carnitine-tcell-cpt-loss Genetic tests limit broad claims about carnitine-shuttle dependence of immunity. T-cell-specific Cpt1a deletion showed that the ACC2/Cpt1a pathway was largely dispensable for memory and regulatory T-cell formation in the tested models. Model: Mouse T-cell conditional knockout and differentiation/infection experiments. Limitations: Does not exclude other tissue or immune contexts. Evidence access: Primary abstract and full-text mouse genetic methods Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043753/ · DOI 10.1016/j.cmet.2018.06.002
Complete structured claim and evidence
Expressing mouse ATB0,+ in HRPE cells enabled carnitine transport requiring both sodium and chloride; activation analysis was consistent with two sodium ions and one chloride ion.
Mouse amino-acid transporter ATB0,+ / Slc6a14 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse colon transporter expressed in human retinal pigment epithelial cells and frog oocytes.
limitations
The transporter is mouse-derived even in a human host cell; dietary sodium/chloride effects were not tested.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A second uptake route couples carnitine to both salt ions.
primary_references
Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11306651/ · DOI 10.1111/j.1469-7793.2001.0297f.x
transport_effect
raises Carnitine transport requiring both sodium and chloride, which is inward.
transport_pool
the expressing cell Carnitine transport requiring both sodium and chloride, which is inward.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 466–472
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse colon transporter expressed in human retinal pigment epithelial cells and frog oocytes. · source_derived_draft · unverified_draft
## l-carnitine-atb-carnitine A second uptake route couples carnitine to both salt ions. Expressing mouse ATB0,+ in HRPE cells enabled carnitine transport requiring both sodium and chloride; activation analysis was consistent with two sodium ions and one chloride ion. Model: Mouse colon transporter expressed in human retinal pigment epithelial cells and frog oocytes. Limitations: The transporter is mouse-derived even in a human host cell; dietary sodium/chloride effects were not tested. Evidence access: Primary abstract Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11306651/ · DOI 10.1111/j.1469-7793.2001.0297f.x
Complete structured claim and evidence
Amino-acid substrates inhibited carnitine transport through expressed mouse ATB0,+.
Mouse amino-acid transporter ATB0,+ / Slc6a14 → Mouse ATB0,+-mediated carnitine transport source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse Slc6a14 heterologous expression assays.
limitations
This finding concerns ATB0,+, not OCTN2; in vitro competition does not establish a meal or supplement interaction.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Some amino acids share and compete for this transport route.
primary_references
Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11306651/ · DOI 10.1111/j.1469-7793.2001.0297f.x
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 474–480
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse Slc6a14 heterologous expression assays. · source_derived_draft · unverified_draft
## l-carnitine-atb-competition Some amino acids share and compete for this transport route. Amino-acid substrates inhibited carnitine transport through expressed mouse ATB0,+. Model: Mouse Slc6a14 heterologous expression assays. Limitations: This finding concerns ATB0,+, not OCTN2; in vitro competition does not establish a meal or supplement interaction. Evidence access: Primary abstract Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11306651/ · DOI 10.1111/j.1469-7793.2001.0297f.x
Complete structured claim and evidence
Human CT2 expressed in Xenopus oocytes mediated high-affinity carnitine transport; tissue staining located CT2 in epididymal luminal membranes and Sertoli cells.
Human carnitine transporter CT2 / SLC22A16 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human transporter cloning, oocyte transport and tissue immunohistochemistry.
limitations
Transport/localization do not establish improved fertility from carnitine supplements.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A distinct transporter connects carnitine with the reproductive tract.
primary_references
Molecular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12089149/ · DOI 10.1074/jbc.M203883200
transport_effect
raises High-affinity carnitine transport measured in expressing oocytes.
transport_pool
the expressing cell High-affinity carnitine transport measured in expressing oocytes.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 482–488
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human transporter cloning, oocyte transport and tissue immunohistochemistry. · source_derived_draft · unverified_draft
## l-carnitine-ct2-transport A distinct transporter connects carnitine with the reproductive tract. Human CT2 expressed in Xenopus oocytes mediated high-affinity carnitine transport; tissue staining located CT2 in epididymal luminal membranes and Sertoli cells. Model: Human transporter cloning, oocyte transport and tissue immunohistochemistry. Limitations: Transport/localization do not establish improved fertility from carnitine supplements. Evidence access: Primary abstract Molecular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12089149/ · DOI 10.1074/jbc.M203883200
Complete structured claim and evidence
Human OCTN2 cryo-EM structures identified a sodium-binding cavity separate from the carnitine site, with allosteric coupling supported by electrophysiology.
Sodium ion → Human OCTN2 allosteric sodium-binding site source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human OCTN2 structures in ligand-free, carnitine/sodium-bound and ipratropium-bound conformations; 2025 primary study.
limitations
Structural coupling does not show that more sodium intake increases transport.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Sodium supports transport through a separate coupled binding site.
primary_references
Structural basis of sodium ion-dependent carnitine transport by OCTN2. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41318751/ · DOI 10.1038/s41467-025-66867-6
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 490–496
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human OCTN2 structures in ligand-free, carnitine/sodium-bound and ipratropium-bound conformations; 2025 primary study. · source_derived_draft · unverified_draft
## l-carnitine-octn2-structure Sodium supports transport through a separate coupled binding site. Human OCTN2 cryo-EM structures identified a sodium-binding cavity separate from the carnitine site, with allosteric coupling supported by electrophysiology. Model: Human OCTN2 structures in ligand-free, carnitine/sodium-bound and ipratropium-bound conformations; 2025 primary study. Limitations: Structural coupling does not show that more sodium intake increases transport. Evidence access: Primary abstract Structural basis of sodium ion-dependent carnitine transport by OCTN2. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41318751/ · DOI 10.1038/s41467-025-66867-6
Complete structured claim and evidence
Purified recombinant human CRAT transferred short-chain acyl groups including acetyl from acyl-CoA substrates to carnitine in enzyme assays.
Human carnitine acetyltransferase / CRAT → Acetyl-L-carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Table 1 and recombinant enzyme methods
experimental_model
Human CRAT expressed in E. coli; steady-state kinetic substrate panel.
limitations
Purified-enzyme capacity does not identify the dominant flux in every compartment.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The human enzyme directly connects carnitine and the CoA pool.
primary_references
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 498–504
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human CRAT expressed in E. coli; steady-state kinetic substrate panel. · source_derived_draft · unverified_draft
## l-carnitine-human-crat-reaction The human enzyme directly connects carnitine and the CoA pool. Purified recombinant human CRAT transferred short-chain acyl groups including acetyl from acyl-CoA substrates to carnitine in enzyme assays. Model: Human CRAT expressed in E. coli; steady-state kinetic substrate panel. Limitations: Purified-enzyme capacity does not identify the dominant flux in every compartment. Evidence access: Primary full-text Table 1 and recombinant enzyme methods Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
Complete structured claim and evidence
Adding palmitoylcarnitine impaired mitochondrial membrane potential and spare respiratory capacity in leukocytes from healthy donors.
Palmitoyl-L-carnitine → Human leukocyte respiration during palmitoylcarnitine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text PBMC exposure methods and results
experimental_model
Human donor leukocytes ex vivo; a separate cohort comparison measured acylcarnitines in decompensated cirrhosis.
limitations
PBMCs were exposed to 2.5-25 micromolar palmitoylcarnitine for four hours; this is not equivalent to taking free L-carnitine.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A loaded carnitine molecule can have effects beyond carrying fuel.
primary_references
Palmitoylcarnitine impairs immunity in decompensated cirrhosis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39524205/ · DOI 10.1016/j.jhepr.2024.101187
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 506–512
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human donor leukocytes ex vivo; a separate cohort comparison measured acylcarnitines in decompensated cirrhosis. · source_derived_draft · unverified_draft
## l-carnitine-acyl-immune-respiration A loaded carnitine molecule can have effects beyond carrying fuel. Adding palmitoylcarnitine impaired mitochondrial membrane potential and spare respiratory capacity in leukocytes from healthy donors. Model: Human donor leukocytes ex vivo; a separate cohort comparison measured acylcarnitines in decompensated cirrhosis. Limitations: PBMCs were exposed to 2.5-25 micromolar palmitoylcarnitine for four hours; this is not equivalent to taking free L-carnitine. Evidence access: Primary abstract and full-text PBMC exposure methods and results Palmitoylcarnitine impairs immunity in decompensated cirrhosis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39524205/ · DOI 10.1016/j.jhepr.2024.101187
Complete structured claim and evidence
Palmitoylcarnitine exposure increased CXCL8 expression and IL-8 release in human donor leukocytes.
Palmitoyl-L-carnitine → Human leukocyte IL-8 release during palmitoylcarnitine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text PBMC exposure methods and results
experimental_model
Human PBMCs; 2.5-25 micromolar dose range, four-hour exposure.
limitations
Does not prove a clinical inflammatory effect of carnitine supplements.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The acylated molecule can promote an inflammatory response in cells.
primary_references
Palmitoylcarnitine impairs immunity in decompensated cirrhosis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39524205/ · DOI 10.1016/j.jhepr.2024.101187
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 514–520
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human PBMCs; 2.5-25 micromolar dose range, four-hour exposure. · source_derived_draft · unverified_draft
## l-carnitine-acyl-immune-cytokine The acylated molecule can promote an inflammatory response in cells. Palmitoylcarnitine exposure increased CXCL8 expression and IL-8 release in human donor leukocytes. Model: Human PBMCs; 2.5-25 micromolar dose range, four-hour exposure. Limitations: Does not prove a clinical inflammatory effect of carnitine supplements. Evidence access: Primary abstract and full-text PBMC exposure methods and results Palmitoylcarnitine impairs immunity in decompensated cirrhosis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39524205/ · DOI 10.1016/j.jhepr.2024.101187
Complete structured claim and evidence
Albumin reduced palmitoylcarnitine-associated oxidative stress and membrane-potential impairment in donor leukocytes.
Human serum albumin → Human leukocyte oxidative stress during palmitoylcarnitine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text PBMC exposure methods and results
experimental_model
Human PBMCs with 5 mg/ml human serum albumin, given 30 minutes before or alongside the four-hour exposure.
limitations
This comparison does not by itself prove a binding mechanism or clinical efficacy.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The surrounding protein environment changed the observed effect.
primary_references
Palmitoylcarnitine impairs immunity in decompensated cirrhosis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39524205/ · DOI 10.1016/j.jhepr.2024.101187
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 522–528
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human PBMCs with 5 mg/ml human serum albumin, given 30 minutes before or alongside the four-hour exposure. · source_derived_draft · unverified_draft
## l-carnitine-acyl-albumin The surrounding protein environment changed the observed effect. Albumin reduced palmitoylcarnitine-associated oxidative stress and membrane-potential impairment in donor leukocytes. Model: Human PBMCs with 5 mg/ml human serum albumin, given 30 minutes before or alongside the four-hour exposure. Limitations: This comparison does not by itself prove a binding mechanism or clinical efficacy. Evidence access: Primary abstract and full-text PBMC exposure methods and results Palmitoylcarnitine impairs immunity in decompensated cirrhosis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39524205/ · DOI 10.1016/j.jhepr.2024.101187
Complete structured claim and evidence
Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis.
Protein-bound N-epsilon-trimethyllysine residues → Free N-epsilon-trimethyl-L-lysine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Radiolabeled asialofetuin metabolism in rats and perfused rat liver
limitations
Direct tracer evidence is rat; do not replace this with a direct free-lysine-to-carnitine edge.
organism
Rattus norvegicus
plain_language
Protein breakdown releases the modified lysine used to make carnitine.
primary_references
[labadie1976] Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976). https://pubmed.ncbi.nlm.nih.gov/64247/ DOI: 10.1042/bj1600085
tissue_or_cell_type
Liver lysosomes and downstream metabolism
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 156–164
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled asialofetuin metabolism in rats and perfused rat liver · source_derived_draft · unverified_draft
### protein-tml-release Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis. Plain language: Protein breakdown releases the modified lysine used to make carnitine. Condition category: normal organism: Rattus norvegicus tissue_or_cell_type: Liver lysosomes and downstream metabolism experimental_model: Radiolabeled asialofetuin metabolism in rats and perfused rat liver limitations: Direct tracer evidence is rat; do not replace this with a direct free-lysine-to-carnitine edge. [labadie1976] Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976). https://pubmed.ncbi.nlm.nih.gov/64247/ DOI: 10.1042/bj1600085
Complete structured claim and evidence
Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.
Free N-epsilon-trimethyl-L-lysine → (2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays
limitations
The substrate is free trimethyllysine after proteolysis, not ordinary free lysine.
organism
Homo sapiens
plain_language
TMLHE begins conversion of released trimethyllysine toward carnitine.
primary_references
[lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A
tissue_or_cell_type
Mitochondrial carnitine-biosynthesis step
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 166–175
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays · source_derived_draft · unverified_draft
### tmlhe-hydroxylation Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation. Plain language: TMLHE begins conversion of released trimethyllysine toward carnitine. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial carnitine-biosynthesis step experimental_model: Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays limitations: The substrate is free trimethyllysine after proteolysis, not ordinary free lysine. [lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A
Complete structured claim and evidence
Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine.
(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine → 4-Trimethylaminobutyraldehyde source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human enzyme; NMR and coupled activity assays
limitations
Whole-body flux contribution remains unquantified.
organism
Homo sapiens
plain_language
SHMT1 can perform the second carnitine-synthesis reaction.
primary_references
[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
tissue_or_cell_type
Cytosolic enzyme tested in vitro
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 177–185
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme; NMR and coupled activity assays · source_derived_draft · unverified_draft
### shmt1-html-cleavage Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine. Plain language: SHMT1 can perform the second carnitine-synthesis reaction. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic enzyme tested in vitro experimental_model: Purified human enzyme; NMR and coupled activity assays limitations: Whole-body flux contribution remains unquantified. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
Complete structured claim and evidence
Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1.
(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine → 4-Trimethylaminobutyraldehyde source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human enzyme kinetic assay
limitations
Mouse Tha1 specialization should not be assigned to a human THA1 enzyme.
organism
Homo sapiens
plain_language
SHMT2 provides another demonstrated aldolase activity.
primary_references
[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
tissue_or_cell_type
Mitochondrial enzyme tested in vitro
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 187–195
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme kinetic assay · source_derived_draft · unverified_draft
### shmt2-html-cleavage Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1. Plain language: SHMT2 provides another demonstrated aldolase activity. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial enzyme tested in vitro experimental_model: Purified human enzyme kinetic assay limitations: Mouse Tha1 specialization should not be assigned to a human THA1 enzyme. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
Complete structured claim and evidence
BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron.
gamma-Butyrobetaine → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human cDNA expression and human tissue activity assays
limitations
Do not generalize full carnitine-synthesis capacity to every tissue.
organism
Homo sapiens
plain_language
BBOX1 completes carnitine synthesis.
primary_references
[vaz1998] Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase (1998). https://pubmed.ncbi.nlm.nih.gov/9753662/ DOI: 10.1006/bbrc.1998.9343 [rebouche1980] Tissue distribution of carnitine biosynthetic enzymes in man (1980). https://pubmed.ncbi.nlm.nih.gov/6770910/ DOI: 10.1016/0304-4165(80)90133-6
tissue_or_cell_type
Kidney, liver and brain; abundance differs
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 207–216
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA expression and human tissue activity assays · source_derived_draft · unverified_draft
### bbox1-carnitine-formation BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron. Plain language: BBOX1 completes carnitine synthesis. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Kidney, liver and brain; abundance differs experimental_model: Human cDNA expression and human tissue activity assays limitations: Do not generalize full carnitine-synthesis capacity to every tissue. [vaz1998] Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase (1998). https://pubmed.ncbi.nlm.nih.gov/9753662/ DOI: 10.1006/bbrc.1998.9343 [rebouche1980] Tissue distribution of carnitine biosynthetic enzymes in man (1980). https://pubmed.ncbi.nlm.nih.gov/6770910/ DOI: 10.1016/0304-4165(80)90133-6
Complete structured claim and evidence
Omission controls with recombinant human MBP-TMLH-a showed that ascorbate, Fe(II) and 2-oxoglutarate were each needed for efficient conversion of free trimethyllysine to 3-hydroxytrimethyllysine.
L-Ascorbate → Trimethyllysine hydroxylase / TMLHE source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C + iron support hydroxylation of a modified lysine precursor; downstream existing SHMT steps use B6-derived PLP and ALDH9A1 uses NAD+.
experimental_model
Recombinant human MBP-TMLH-a; mass spectrometry and NMR
exposure
500 micromolar trimethyllysine and 3 micromolar enzyme, FeSO4/2OG/ascorbate, 37 C for 30 minutes; cofactor omission controls.
limitations
New record isolates the ascorbate cofactor dependence; the existing substrate-to-product UUID is reused. Fusion-protein assay does not quantify whole-body flux.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
The first carnitine-synthesis hydroxylation needs vitamin C support alongside iron and 2-oxoglutarate.
primary_references
[tmlh2016] Substrate scope for trimethyllysine hydroxylase catalysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27730239/ DOI: 10.1039/c6cc07845a
tissue_or_cell_type
Cell-free recombinant enzyme
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 689–700
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MBP-TMLH-a; mass spectrometry and NMR · source_derived_draft · unverified_draft
### vc-enzyme-tmlh-ascorbate-dependency Omission controls with recombinant human MBP-TMLH-a showed that ascorbate, Fe(II) and 2-oxoglutarate were each needed for efficient conversion of free trimethyllysine to 3-hydroxytrimethyllysine. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first carnitine-synthesis hydroxylation needs vitamin C support alongside iron and 2-oxoglutarate. organism: Homo sapiens tissue_or_cell_type: Cell-free recombinant enzyme experimental_model: Recombinant human MBP-TMLH-a; mass spectrometry and NMR limitations: New record isolates the ascorbate cofactor dependence; the existing substrate-to-product UUID is reused. Fusion-protein assay does not quantify whole-body flux. cross_nutrient: Vitamin C + iron support hydroxylation of a modified lysine precursor; downstream existing SHMT steps use B6-derived PLP and ALDH9A1 uses NAD+. exposure: 500 micromolar trimethyllysine and 3 micromolar enzyme, FeSO4/2OG/ascorbate, 37 C for 30 minutes; cofactor omission controls. [tmlh2016] Substrate scope for trimethyllysine hydroxylase catalysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27730239/ DOI: 10.1039/c6cc07845a
Complete structured claim and evidence
Increasing ascorbate supplementation increased carnitine accumulation from gamma-butyrobetaine in primary guinea-pig hepatocytes after four hours.
L-Ascorbate → Guinea-pig hepatocyte carnitine content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Primary cultured male guinea-pig hepatocyte monolayers
exposure
Ascorbate preloading followed by 4-hour gamma-butyrobetaine incubation; precursor range includes 0.05–1.0 mM and 5 mM.
limitations
Species-specific cell exposure; accumulation reflects production and other handling, not directly a human dietary dose-response.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Cavia porcellus
plain_language
Vitamin C helped isolated liver cells convert a supplied precursor into carnitine.
primary_references
[hepatocytes1991] The regulatory effect of ascorbate on the carnitine synthesis in primary cultured guinea pig hepatocytes. (1991). https://pubmed.ncbi.nlm.nih.gov/1765841/ DOI: 10.3177/jnsv.37.371
tissue_or_cell_type
Hepatocytes
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 702–713
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary cultured male guinea-pig hepatocyte monolayers · source_derived_draft · unverified_draft
### vc-enzyme-hepatocyte-carnitine Increasing ascorbate supplementation increased carnitine accumulation from gamma-butyrobetaine in primary guinea-pig hepatocytes after four hours. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C helped isolated liver cells convert a supplied precursor into carnitine. organism: Cavia porcellus tissue_or_cell_type: Hepatocytes experimental_model: Primary cultured male guinea-pig hepatocyte monolayers limitations: Species-specific cell exposure; accumulation reflects production and other handling, not directly a human dietary dose-response. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Ascorbate preloading followed by 4-hour gamma-butyrobetaine incubation; precursor range includes 0.05–1.0 mM and 5 mM. [hepatocytes1991] The regulatory effect of ascorbate on the carnitine synthesis in primary cultured guinea pig hepatocytes. (1991). https://pubmed.ncbi.nlm.nih.gov/1765841/ DOI: 10.3177/jnsv.37.371
Complete structured claim and evidence
Gamma-butyrobetaine supplementation lowered both reduced and total cellular vitamin C content during the guinea-pig hepatocyte carnitine-synthesis experiment.
gamma-Butyrobetaine → Guinea-pig hepatocyte ascorbate content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Primary cultured male guinea-pig hepatocyte monolayers
exposure
Ascorbate preloading followed by 4-hour gamma-butyrobetaine incubation; precursor range includes 0.05–1.0 mM and 5 mM.
limitations
Pool decrease alone does not establish exact ascorbate stoichiometry or identify all oxidation, export and degradation pathways.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Cavia porcellus
plain_language
Supplying the carnitine precursor lowered the cells’ measured vitamin C pools.
primary_references
[hepatocytes1991] The regulatory effect of ascorbate on the carnitine synthesis in primary cultured guinea pig hepatocytes. (1991). https://pubmed.ncbi.nlm.nih.gov/1765841/ DOI: 10.3177/jnsv.37.371
tissue_or_cell_type
Hepatocytes
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 715–726
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary cultured male guinea-pig hepatocyte monolayers · source_derived_draft · unverified_draft
### vc-enzyme-precursor-lowers-cell-ascorbate Gamma-butyrobetaine supplementation lowered both reduced and total cellular vitamin C content during the guinea-pig hepatocyte carnitine-synthesis experiment. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying the carnitine precursor lowered the cells’ measured vitamin C pools. organism: Cavia porcellus tissue_or_cell_type: Hepatocytes experimental_model: Primary cultured male guinea-pig hepatocyte monolayers limitations: Pool decrease alone does not establish exact ascorbate stoichiometry or identify all oxidation, export and degradation pathways. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Ascorbate preloading followed by 4-hour gamma-butyrobetaine incubation; precursor range includes 0.05–1.0 mM and 5 mM. [hepatocytes1991] The regulatory effect of ascorbate on the carnitine synthesis in primary cultured guinea pig hepatocytes. (1991). https://pubmed.ncbi.nlm.nih.gov/1765841/ DOI: 10.3177/jnsv.37.371
Complete structured claim and evidence
Guinea pigs with tissue vitamin C around 12% saturation had significantly lower muscle carnitine than animals near 100% saturation, without the customary overt hypovitaminosis-C signs in this experiment.
Vitamin C → Guinea-pig muscle carnitine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Guinea pigs with graded dietary vitamin C supply
exposure
Dietary regimens produced tissue vitamin C approximately 12% versus 100% saturation; regimen duration/dose not verified in abstract.
limitations
No direct synthesis-rate measurement; suggested explanation for human fatigue was not tested.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Cavia porcellus
plain_language
Low vitamin C coincided with lower muscle carnitine before obvious scurvy signs in these animals.
primary_references
[carnitine1980] Dietary ascorbic acid and muscle carnitine (beta-OH-gamma-(trimethylamino) butyric acid) in guinea-pigs. (1980). https://pubmed.ncbi.nlm.nih.gov/7378344/ DOI: 10.1079/bjn19800102
tissue_or_cell_type
Skeletal muscle
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 728–739
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Guinea pigs with graded dietary vitamin C supply · source_derived_draft · unverified_draft
### vc-enzyme-low-c-muscle-carnitine Guinea pigs with tissue vitamin C around 12% saturation had significantly lower muscle carnitine than animals near 100% saturation, without the customary overt hypovitaminosis-C signs in this experiment. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low vitamin C coincided with lower muscle carnitine before obvious scurvy signs in these animals. organism: Cavia porcellus tissue_or_cell_type: Skeletal muscle experimental_model: Guinea pigs with graded dietary vitamin C supply limitations: No direct synthesis-rate measurement; suggested explanation for human fatigue was not tested. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Dietary regimens produced tissue vitamin C approximately 12% versus 100% saturation; regimen duration/dose not verified in abstract. [carnitine1980] Dietary ascorbic acid and muscle carnitine (beta-OH-gamma-(trimethylamino) butyric acid) in guinea-pigs. (1980). https://pubmed.ncbi.nlm.nih.gov/7378344/ DOI: 10.1079/bjn19800102
Complete structured claim and evidence
Oral trimethyllysine increased urine-based estimated carnitine synthesis by 32–40 micromol/kg/day across ascorbate-replete, deficient and pair-fed guinea-pig groups; vitamin C deficiency did not abolish the precursor response.
Free N-epsilon-trimethyl-L-lysine → Guinea-pig carnitine synthesis estimated from urinary output source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Guinea-pig dietary deficiency with pair feeding and precursor loading
exposure
Vitamin C deficient diet for 28 days; oral trimethyllysine or gamma-butyrobetaine 0.5 mmol/kg/day on days 19–28, with replete and pair-fed controls.
limitations
Estimate is derived from excretion during a large precursor load, not isotope-resolved basal flux; does not show all tissues are vitamin-C-independent.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Cavia porcellus
plain_language
Even vitamin-C-deficient animals could make substantial carnitine when given this precursor.
primary_references
[carnitine1995] The ability of guinea pigs to synthesize carnitine at a normal rate from epsilon-N-trimethyllysine or gamma-butyrobetaine in vivo is not compromised by experimental vitamin C deficiency. (1995). https://pubmed.ncbi.nlm.nih.gov/7752911/ DOI: 10.1016/0026-0495(95)90120-5
tissue_or_cell_type
Whole animal; urine-based synthesis estimate
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 754–765
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Guinea-pig dietary deficiency with pair feeding and precursor loading · source_derived_draft · unverified_draft
### vc-enzyme-deficient-tml-response Oral trimethyllysine increased urine-based estimated carnitine synthesis by 32–40 micromol/kg/day across ascorbate-replete, deficient and pair-fed guinea-pig groups; vitamin C deficiency did not abolish the precursor response. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Even vitamin-C-deficient animals could make substantial carnitine when given this precursor. organism: Cavia porcellus tissue_or_cell_type: Whole animal; urine-based synthesis estimate experimental_model: Guinea-pig dietary deficiency with pair feeding and precursor loading limitations: Estimate is derived from excretion during a large precursor load, not isotope-resolved basal flux; does not show all tissues are vitamin-C-independent. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Vitamin C deficient diet for 28 days; oral trimethyllysine or gamma-butyrobetaine 0.5 mmol/kg/day on days 19–28, with replete and pair-fed controls. [carnitine1995] The ability of guinea pigs to synthesize carnitine at a normal rate from epsilon-N-trimethyllysine or gamma-butyrobetaine in vivo is not compromised by experimental vitamin C deficiency. (1995). https://pubmed.ncbi.nlm.nih.gov/7752911/ DOI: 10.1016/0026-0495(95)90120-5
Complete structured claim and evidence
Oral gamma-butyrobetaine increased urine-based estimated carnitine synthesis by 41–50 micromol/kg/day across ascorbate-replete, deficient and pair-fed guinea-pig groups; vitamin C deficiency did not abolish the precursor response.
gamma-Butyrobetaine → Guinea-pig carnitine synthesis estimated from urinary output source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Guinea-pig dietary deficiency with pair feeding and precursor loading
exposure
Vitamin C deficient diet for 28 days; oral trimethyllysine or gamma-butyrobetaine 0.5 mmol/kg/day on days 19–28, with replete and pair-fed controls.
limitations
Estimate is derived from excretion during a large precursor load, not isotope-resolved basal flux; does not show all tissues are vitamin-C-independent.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Cavia porcellus
plain_language
Even vitamin-C-deficient animals could make substantial carnitine when given this precursor.
primary_references
[carnitine1995] The ability of guinea pigs to synthesize carnitine at a normal rate from epsilon-N-trimethyllysine or gamma-butyrobetaine in vivo is not compromised by experimental vitamin C deficiency. (1995). https://pubmed.ncbi.nlm.nih.gov/7752911/ DOI: 10.1016/0026-0495(95)90120-5
tissue_or_cell_type
Whole animal; urine-based synthesis estimate
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 767–778
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Guinea-pig dietary deficiency with pair feeding and precursor loading · source_derived_draft · unverified_draft
### vc-enzyme-deficient-bb-response Oral gamma-butyrobetaine increased urine-based estimated carnitine synthesis by 41–50 micromol/kg/day across ascorbate-replete, deficient and pair-fed guinea-pig groups; vitamin C deficiency did not abolish the precursor response. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Even vitamin-C-deficient animals could make substantial carnitine when given this precursor. organism: Cavia porcellus tissue_or_cell_type: Whole animal; urine-based synthesis estimate experimental_model: Guinea-pig dietary deficiency with pair feeding and precursor loading limitations: Estimate is derived from excretion during a large precursor load, not isotope-resolved basal flux; does not show all tissues are vitamin-C-independent. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Vitamin C deficient diet for 28 days; oral trimethyllysine or gamma-butyrobetaine 0.5 mmol/kg/day on days 19–28, with replete and pair-fed controls. [carnitine1995] The ability of guinea pigs to synthesize carnitine at a normal rate from epsilon-N-trimethyllysine or gamma-butyrobetaine in vivo is not compromised by experimental vitamin C deficiency. (1995). https://pubmed.ncbi.nlm.nih.gov/7752911/ DOI: 10.1016/0026-0495(95)90120-5
Complete structured claim and evidence
Without carnitine-precursor supplements, vitamin-C-deficient guinea pigs excreted approximately three times as much free and total carnitine as replete animals on days 19–28; pair feeding alone did not produce that pattern.
Vitamin C → Guinea-pig urinary carnitine excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Guinea-pig dietary deficiency with pair feeding and precursor loading
exposure
Vitamin C deficient diet for 28 days; oral trimethyllysine or gamma-butyrobetaine 0.5 mmol/kg/day on days 19–28, with replete and pair-fed controls.
limitations
Authors favored excessive excretion as an explanation for depletion; this does not isolate a renal transporter or quantify its contribution in human deficiency.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Cavia porcellus
plain_language
Greater loss in urine can contribute to low carnitine during vitamin C deficiency.
primary_references
[carnitine1995] The ability of guinea pigs to synthesize carnitine at a normal rate from epsilon-N-trimethyllysine or gamma-butyrobetaine in vivo is not compromised by experimental vitamin C deficiency. (1995). https://pubmed.ncbi.nlm.nih.gov/7752911/ DOI: 10.1016/0026-0495(95)90120-5
tissue_or_cell_type
Whole animal; urine-based synthesis estimate
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 780–791
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Guinea-pig dietary deficiency with pair feeding and precursor loading · source_derived_draft · unverified_draft
### vc-enzyme-deficient-carnitine-excretion Without carnitine-precursor supplements, vitamin-C-deficient guinea pigs excreted approximately three times as much free and total carnitine as replete animals on days 19–28; pair feeding alone did not produce that pattern. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Greater loss in urine can contribute to low carnitine during vitamin C deficiency. organism: Cavia porcellus tissue_or_cell_type: Whole animal; urine-based synthesis estimate experimental_model: Guinea-pig dietary deficiency with pair feeding and precursor loading limitations: Authors favored excessive excretion as an explanation for depletion; this does not isolate a renal transporter or quantify its contribution in human deficiency. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Vitamin C deficient diet for 28 days; oral trimethyllysine or gamma-butyrobetaine 0.5 mmol/kg/day on days 19–28, with replete and pair-fed controls. [carnitine1995] The ability of guinea pigs to synthesize carnitine at a normal rate from epsilon-N-trimethyllysine or gamma-butyrobetaine in vivo is not compromised by experimental vitamin C deficiency. (1995). https://pubmed.ncbi.nlm.nih.gov/7752911/ DOI: 10.1016/0026-0495(95)90120-5
Complete structured claim and evidence
Palmitoylcarnitine antagonized acetyl-CoA inhibition of human PANK2, providing a positive regulatory input in biochemical assays.
Palmitoyl-L-carnitine → Human pantothenate kinase 2 / PANK2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Human PANK2 in 293T-cell lysates and purified enzyme assays
exposure
Human PANK2 in 293T lysates and purified-enzyme assays; indexed Fig. 1 used 0.2 micromolar acetyl-CoA.
limitations
Acylcarnitine is a specific molecule; this does not show that free-carnitine supplements activate PANK2 in people. Intact-organism fatty-acid-demand interpretation was proposed.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
A long-chain acylcarnitine can release the brake on PANK2.
primary_references
[b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 613–624
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PANK2 in 293T-cell lysates and purified enzyme assays · source_derived_draft · unverified_draft
### b5-bio-pank2-palmitoylcarnitine Palmitoylcarnitine antagonized acetyl-CoA inhibition of human PANK2, providing a positive regulatory input in biochemical assays. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A long-chain acylcarnitine can release the brake on PANK2. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human PANK2 in 293T-cell lysates and purified enzyme assays limitations: Acylcarnitine is a specific molecule; this does not show that free-carnitine supplements activate PANK2 in people. Intact-organism fatty-acid-demand interpretation was proposed. exposure: Human PANK2 in 293T lysates and purified-enzyme assays; indexed Fig. 1 used 0.2 micromolar acetyl-CoA. cross_nutrient: true [b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104
Complete structured claim and evidence
Free carnitine did not activate purified human PANK2 in the experiment shown in Fig. 4B.
L-Carnitine → Human pantothenate kinase 2 / PANK2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Human PANK2 in 293T-cell lysates and purified enzyme assays
exposure
Primary Fig. 4B purified-enzyme assay; carnitine concentration range not extracted.
limitations
The same paper observed free-carnitine activation in lysate preparations at higher concentrations, so the purified-enzyme negative result must not be generalized to every lysate condition. Neither assay tests clinical carnitine supplementation.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
The purified enzyme did not respond directly to free carnitine.
primary_references
[b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 626–637
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PANK2 in 293T-cell lysates and purified enzyme assays · source_derived_draft · unverified_draft
### b5-bio-pank2-free-carnitine Free carnitine did not activate purified human PANK2 in the experiment shown in Fig. 4B. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The purified enzyme did not respond directly to free carnitine. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human PANK2 in 293T-cell lysates and purified enzyme assays limitations: The same paper observed free-carnitine activation in lysate preparations at higher concentrations, so the purified-enzyme negative result must not be generalized to every lysate condition. Neither assay tests clinical carnitine supplementation. exposure: Primary Fig. 4B purified-enzyme assay; carnitine concentration range not extracted. cross_nutrient: true [b5-bio-pank2reg] Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. (2007). https://pubmed.ncbi.nlm.nih.gov/17242360/ DOI: 10.1073/pnas.0607621104
Complete structured claim and evidence
Biotin-deficient but carnitine-sufficient HepG2 cells had more than tenfold higher intracellular 3-hydroxyisovalerylcarnitine than doubly sufficient cells.
Biotin → HepG2 3-hydroxyisovalerylcarnitine pool source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/biotin-research/25527659.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f", "start_char": 0, "end_char": 2372, "text_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f"}
experimental_model
Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells
exposure
Separate and combined biotin and carnitine depletion
limitations
This is a cell-culture demonstration of marker masking; it does not validate a diagnostic correction formula in pregnancy or the general population.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
When carnitine is available, the biotin-related bottleneck produces a strong side-product signal.
primary_references
[b7-p25527659] In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/25527659/ DOI: 10.3945/jn.114.201343
tissue_or_cell_type
HepG2 hepatoma cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 949–960
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells · source_derived_draft · unverified_draft
### b7-c5oh-biotin-low Biotin-deficient but carnitine-sufficient HepG2 cells had more than tenfold higher intracellular 3-hydroxyisovalerylcarnitine than doubly sufficient cells. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: When carnitine is available, the biotin-related bottleneck produces a strong side-product signal. organism: Homo sapiens tissue_or_cell_type: HepG2 hepatoma cells experimental_model: Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells limitations: This is a cell-culture demonstration of marker masking; it does not validate a diagnostic correction formula in pregnancy or the general population. exposure: Separate and combined biotin and carnitine depletion evidence_span: {"source_cache": "artifacts/biotin-research/25527659.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f", "start_char": 0, "end_char": 2372, "text_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f"} [b7-p25527659] In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/25527659/ DOI: 10.3945/jn.114.201343
Complete structured claim and evidence
Combined biotin and carnitine deficiency largely masked the increase in substrate-derived acylcarnitines observed with isolated biotin deficiency in HepG2 cells.
L-Carnitine → HepG2 3-hydroxyisovalerylcarnitine pool source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/biotin-research/25527659.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f", "start_char": 0, "end_char": 2372, "text_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f"}
experimental_model
Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells
exposure
Separate and combined biotin and carnitine depletion
limitations
This is a cell-culture demonstration of marker masking; it does not validate a diagnostic correction formula in pregnancy or the general population.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
A second shortage can hide the laboratory signature of the first.
primary_references
[b7-p25527659] In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/25527659/ DOI: 10.3945/jn.114.201343
tissue_or_cell_type
HepG2 hepatoma cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 962–973
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells · source_derived_draft · unverified_draft
### b7-carnitine-hides-c5oh Combined biotin and carnitine deficiency largely masked the increase in substrate-derived acylcarnitines observed with isolated biotin deficiency in HepG2 cells. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second shortage can hide the laboratory signature of the first. organism: Homo sapiens tissue_or_cell_type: HepG2 hepatoma cells experimental_model: Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells limitations: This is a cell-culture demonstration of marker masking; it does not validate a diagnostic correction formula in pregnancy or the general population. exposure: Separate and combined biotin and carnitine depletion evidence_span: {"source_cache": "artifacts/biotin-research/25527659.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f", "start_char": 0, "end_char": 2372, "text_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f"} [b7-p25527659] In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/25527659/ DOI: 10.3945/jn.114.201343
Complete structured claim and evidence
Carnitine repletion of doubly deficient HepG2 cells increased acetylcarnitine, propionylcarnitine and 3-hydroxyisovalerylcarnitine each by more than 50-fold.
L-Carnitine → HepG2 acylcarnitine response to carnitine repletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/biotin-research/25527659.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f", "start_char": 0, "end_char": 2372, "text_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f"}
experimental_model
Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells
exposure
Separate and combined biotin and carnitine depletion
limitations
This is a cell-culture demonstration of marker masking; it does not validate a diagnostic correction formula in pregnancy or the general population.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
Restoring carnitine exposed the unresolved biotin-related bottleneck.
primary_references
[b7-p25527659] In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/25527659/ DOI: 10.3945/jn.114.201343
tissue_or_cell_type
HepG2 hepatoma cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 975–986
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells · source_derived_draft · unverified_draft
### b7-carnitine-unmasking Carnitine repletion of doubly deficient HepG2 cells increased acetylcarnitine, propionylcarnitine and 3-hydroxyisovalerylcarnitine each by more than 50-fold. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring carnitine exposed the unresolved biotin-related bottleneck. organism: Homo sapiens tissue_or_cell_type: HepG2 hepatoma cells experimental_model: Two-factor biotin/carnitine depletion and carnitine repletion in human HepG2 cells limitations: This is a cell-culture demonstration of marker masking; it does not validate a diagnostic correction formula in pregnancy or the general population. exposure: Separate and combined biotin and carnitine depletion evidence_span: {"source_cache": "artifacts/biotin-research/25527659.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f", "start_char": 0, "end_char": 2372, "text_sha256": "4a368eb2fa2020bb1cabc99b31a3420870a8256886d5934d3d834c90b078238f"} [b7-p25527659] In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency. (2015). https://pubmed.ncbi.nlm.nih.gov/25527659/ DOI: 10.3945/jn.114.201343
Complete structured claim and evidence
Human OCTN2 expression increased sodium-dependent carnitine uptake with an apparent Km of 4.34 micromolar.
Human carnitine transporter OCTN2 / SLC22A5 → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sodium-research/9685390.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6", "start_char": 0, "end_char": 1549, "text_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6"}
experimental_model
Cloning and functional expression
exposure
Radiolabeled carnitine uptake and sodium dependence
limitations
Expression assay; dietary sodium intake, mitochondrial fatty-acid oxidation and clinical supplementation were not directly tested.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Human OCTN2 in HEK293 cells
plain_language
The sodium gradient helps bring carnitine into cells.
primary_references
[sodium-p9685390] Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. (1998). https://pubmed.ncbi.nlm.nih.gov/9685390/ DOI: 10.1074/jbc.273.32.20378
tissue_or_cell_type
Cell plasma membrane
transport_effect
raises Expression increased sodium-dependent carnitine uptake.
transport_pool
the expressing cell Expression increased sodium-dependent carnitine uptake.
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 616–627
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and functional expression · source_derived_draft · unverified_draft
### sodium-octn2-carnitine Human OCTN2 expression increased sodium-dependent carnitine uptake with an apparent Km of 4.34 micromolar. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium gradient helps bring carnitine into cells. organism: Human OCTN2 in HEK293 cells tissue_or_cell_type: Cell plasma membrane experimental_model: Cloning and functional expression limitations: Expression assay; dietary sodium intake, mitochondrial fatty-acid oxidation and clinical supplementation were not directly tested. exposure: Radiolabeled carnitine uptake and sodium dependence evidence_span: {"source_cache": "artifacts/sodium-research/9685390.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6", "start_char": 0, "end_char": 1549, "text_sha256": "08cdedaad32299795a52b81183d565d2b476b7a190b2af7b950c829f8c11ddf6"} [sodium-p9685390] Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. (1998). https://pubmed.ncbi.nlm.nih.gov/9685390/ DOI: 10.1074/jbc.273.32.20378
Complete structured claim and evidence
Wild-type human CPT1B showed high-affinity malonyl-CoA binding and inhibition in recombinant mitochondrial assays.
Malonyl-CoA → Human carnitine palmitoyltransferase 1B / CPT1B source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/biotin-research/10651636.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e99728ef83700f17a810421385b71ea243576419df807dc4749b588beb01d400", "start_char": 0, "end_char": 1542, "text_sha256": "e99728ef83700f17a810421385b71ea243576419df807dc4749b588beb01d400"}
experimental_model
Human CPT1B wild type and N-terminal deletions expressed in yeast mitochondria
exposure
Malonyl-CoA binding and activity assays
limitations
Expression host is yeast; these data concern human CPT1B, not every CPT1 isoform or a biotin supplementation outcome.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
Malonyl-CoA links the carboxylase pathway to the carnitine-dependent fat-entry step.
primary_references
[b7-p10651636] The first 28 N-terminal amino acid residues of human heart muscle carnitine palmitoyltransferase I are essential for malonyl CoA sensitivity and high-affinity binding. (2000). https://pubmed.ncbi.nlm.nih.gov/10651636/ DOI: 10.1021/bi9918700
tissue_or_cell_type
Recombinant human muscle/heart CPT1B
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 741–752
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CPT1B wild type and N-terminal deletions expressed in yeast mitochondria · source_derived_draft · unverified_draft
### b7-malonyl-cpt1b Wild-type human CPT1B showed high-affinity malonyl-CoA binding and inhibition in recombinant mitochondrial assays. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Malonyl-CoA links the carboxylase pathway to the carnitine-dependent fat-entry step. organism: Homo sapiens tissue_or_cell_type: Recombinant human muscle/heart CPT1B experimental_model: Human CPT1B wild type and N-terminal deletions expressed in yeast mitochondria limitations: Expression host is yeast; these data concern human CPT1B, not every CPT1 isoform or a biotin supplementation outcome. exposure: Malonyl-CoA binding and activity assays evidence_span: {"source_cache": "artifacts/biotin-research/10651636.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e99728ef83700f17a810421385b71ea243576419df807dc4749b588beb01d400", "start_char": 0, "end_char": 1542, "text_sha256": "e99728ef83700f17a810421385b71ea243576419df807dc4749b588beb01d400"} [b7-p10651636] The first 28 N-terminal amino acid residues of human heart muscle carnitine palmitoyltransferase I are essential for malonyl CoA sensitivity and high-affinity binding. (2000). https://pubmed.ncbi.nlm.nih.gov/10651636/ DOI: 10.1021/bi9918700
Complete structured claim and evidence
Purified human ACC2 formed malonyl-CoA from acetyl-CoA in assays varying bicarbonate and ATP.
Human acetyl-CoA carboxylase 2 / ACACB → Acetyl-CoA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/biotin-research/19236960.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bedd791235b10ff5942ef7177b54bca5b2243883da02fb24572691aaf5975be5", "start_char": 0, "end_char": 896, "text_sha256": "bedd791235b10ff5942ef7177b54bca5b2243883da02fb24572691aaf5975be5"}
experimental_model
Steady-state kinetics of purified recombinant human ACC2; LC-MS/MS malonyl-CoA assay
exposure
Bicarbonate, ATP, acetyl-CoA and citrate concentration matrices
limitations
Kinetic constants are assay properties; they do not define a dietary biotin or B5 threshold.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
ACC2 makes the same carbon product as ACC1 but serves a distinct enzyme context.
primary_references
[b7-p19236960] Characterization of recombinant human acetyl-CoA carboxylase-2 steady-state kinetics. (2009). https://pubmed.ncbi.nlm.nih.gov/19236960/ DOI: 10.1016/j.bbapap.2009.02.004
tissue_or_cell_type
Purified human ACC2
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 676–687
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Steady-state kinetics of purified recombinant human ACC2; LC-MS/MS malonyl-CoA assay · source_derived_draft · unverified_draft
### b7-acc2-reaction Purified human ACC2 formed malonyl-CoA from acetyl-CoA in assays varying bicarbonate and ATP. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ACC2 makes the same carbon product as ACC1 but serves a distinct enzyme context. organism: Homo sapiens tissue_or_cell_type: Purified human ACC2 experimental_model: Steady-state kinetics of purified recombinant human ACC2; LC-MS/MS malonyl-CoA assay limitations: Kinetic constants are assay properties; they do not define a dietary biotin or B5 threshold. exposure: Bicarbonate, ATP, acetyl-CoA and citrate concentration matrices evidence_span: {"source_cache": "artifacts/biotin-research/19236960.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bedd791235b10ff5942ef7177b54bca5b2243883da02fb24572691aaf5975be5", "start_char": 0, "end_char": 896, "text_sha256": "bedd791235b10ff5942ef7177b54bca5b2243883da02fb24572691aaf5975be5"} [b7-p19236960] Characterization of recombinant human acetyl-CoA carboxylase-2 steady-state kinetics. (2009). https://pubmed.ncbi.nlm.nih.gov/19236960/ DOI: 10.1016/j.bbapap.2009.02.004
Complete structured claim and evidence
The enzyme comparison demonstrated FMO3-mediated oxidation of TMA to TMAO.
Human flavin-containing monooxygenase 3 → Trimethylamine / TMA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"}
experimental_model
Recombinant FMO comparison, mouse manipulation and human expression analyses
exposure
FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing
limitations
Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human recombinant FMO3 assay
plain_language
The liver-side enzyme processes a product generated by microbial metabolism.
primary_references
[choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
tissue_or_cell_type
Hepatic TMA oxidation
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1114–1125
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FMO comparison, mouse manipulation and human expression analyses · source_derived_draft · unverified_draft
### choline-fmo3-tmao The enzyme comparison demonstrated FMO3-mediated oxidation of TMA to TMAO. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver-side enzyme processes a product generated by microbial metabolism. organism: Human recombinant FMO3 assay tissue_or_cell_type: Hepatic TMA oxidation experimental_model: Recombinant FMO comparison, mouse manipulation and human expression analyses limitations: Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species. exposure: FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing evidence_span: {"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"} [choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
Complete structured claim and evidence
Human PCC supplies (S)-methylmalonyl-CoA by propionyl-CoA carboxylation upstream of the MCEE-MMUT sequence examined in fibroblast assays.
Human propionyl-CoA carboxylase / PCC → Propionyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Indexed primary abstract; Full text Methods 2.6 and Results 3.6; Figure 5
experimental_model
Human fibroblast PCC and coupled-pathway assays
exposure
Propionyl-CoA, ATP and bicarbonate in enzyme pathway
limitations
Pathway assignment combines human PCC characterization with coupled assays; it is not a simultaneous dietary biotin/B12 intervention.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it.
primary_references
[hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021
tissue_or_cell_type
Fibroblasts
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1159–1172
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human fibroblast PCC and coupled-pathway assays · source_derived_draft · unverified_draft
### pcc-carboxylation-upstream-b12 Human PCC supplies (S)-methylmalonyl-CoA by propionyl-CoA carboxylation upstream of the MCEE-MMUT sequence examined in fibroblast assays. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Human fibroblast PCC and coupled-pathway assays limitations: Pathway assignment combines human PCC characterization with coupled assays; it is not a simultaneous dietary biotin/B12 intervention. exposure: Propionyl-CoA, ATP and bicarbonate in enzyme pathway cross_nutrient: true evidence_location: Indexed primary abstract; Full text Methods 2.6 and Results 3.6; Figure 5 [hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021
Complete structured claim and evidence
Adenosylcobalamin-loaded human MMUT converts (R)-methylmalonyl-CoA to succinyl-CoA in the coupled enzyme assay.
Human methylmalonyl-CoA mutase / MMUT → (R)-Methylmalonyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods
experimental_model
Purified human proteins
exposure
AdoCbl-loaded MMUT and methylmalonyl-CoA; thiokinase-coupled readout
limitations
Product formation is a coupled assay; cellular net flux was not measured.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Purified human MMUT used activated B12 to make succinyl-CoA from the matching methylmalonyl-CoA epimer.
primary_references
[mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4
tissue_or_cell_type
Purified protein assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1103–1115
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human proteins · source_derived_draft · unverified_draft
### mmut-isomerizes-r-methylmalonyl-coa Adenosylcobalamin-loaded human MMUT converts (R)-methylmalonyl-CoA to succinyl-CoA in the coupled enzyme assay. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Purified human MMUT used activated B12 to make succinyl-CoA from the matching methylmalonyl-CoA epimer. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Product formation is a coupled assay; cellular net flux was not measured. exposure: AdoCbl-loaded MMUT and methylmalonyl-CoA; thiokinase-coupled readout cross_nutrient: false evidence_location: Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4
Complete structured claim and evidence
A post-bypass patient had fasting hypoglycemia, low BHB and high free fatty acids; carnitine replacement resolved fasting hypoglycemia.
L-Carnitine → Hypoglycemia with inadequate ketone availability source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Cachectic 69-year-old woman, 12 years after gastric bypass; supervised diagnostic fast.
limitations
Single case; impaired mitochondrial transport was inferred. This is not a general carnitine supplement recommendation.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Fat release was not enough when the next transport step appeared limited.
primary_references
Fasting hypoglycaemia secondary to carnitine deficiency: a late consequence of gastric bypass. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34281938/ · DOI 10.1136/bcr-2021-241703
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 168–174
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cachectic 69-year-old woman, 12 years after gastric bypass; supervised diagnostic fast. · source_derived_draft · unverified_draft
## fast-carnitine-case Fat release was not enough when the next transport step appeared limited. A post-bypass patient had fasting hypoglycemia, low BHB and high free fatty acids; carnitine replacement resolved fasting hypoglycemia. Model: Cachectic 69-year-old woman, 12 years after gastric bypass; supervised diagnostic fast. Limitations: Single case; impaired mitochondrial transport was inferred. This is not a general carnitine supplement recommendation. Evidence access: Primary abstract Fasting hypoglycaemia secondary to carnitine deficiency: a late consequence of gastric bypass. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34281938/ · DOI 10.1136/bcr-2021-241703
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Primary transport failure reduces cellular carnitine uptake

Condition: machinery_impairment · Pathogenic SLC22A5 variants.

Normal role: OCTN2 supplies cells with carnitine.

Recorded consequence: Patient fibroblasts lose mediated uptake; normal-gene complementation partially restores it.

Scope: Human fibroblast experiments and a separate long-term cardiac case.

Mitochondrial transport failure blocks the shuttle

Condition: machinery_impairment · Pathogenic SLC25A20 p.Arg133Trp.

Normal role: CACT transfers acylcarnitine across the inner membrane.

Recorded consequence: Reconstituted carrier activity falls.

Scope: Human variant expressed in bacteria and tested in liposomes.

Carnitine deficiency associated with inadequate fasting ketones

Condition: nutrient_deficiency · Acquired carnitine deficiency in a post-bypass patient.

Normal role: Available substrate and intact production, transport and utilization machinery support the fasting fuel transition.

Recorded consequence: A post-bypass patient had fasting hypoglycemia, low BHB and high free fatty acids; carnitine replacement resolved fasting hypoglycemia.

Scope: Mechanism failure relevant to fasting; fasting is the physiological-state collection, not a deficient nutrient.

A downstream enzyme defect causes acylcarnitine accumulation

Condition: machinery_impairment · Inherited CPT2 deficiency plus heat challenge.

Normal role: CPT2 reconverts incoming acylcarnitine to acyl-CoA.

Recorded consequence: Palmitoylcarnitine accumulation increases, especially at 38 degrees C.

Scope: Patient-derived iPSC myocytes.

Exporting excess acyl groups can drain free carnitine

Condition: nutrient_deficiency · Inherited propionic or methylmalonic acid metabolism defects.

Normal role: Carnitine supports acyl-group transfer and disposal.

Recorded consequence: Low free carnitine accompanies urinary acylcarnitine loss and, in tested biopsies, low muscle carnitine.

Scope: Four patients, with two muscle biopsies.

Drug-associated depletion can impair fasting ketone production

Condition: nutrient_deficiency · Twelve days of pivmecillinam exposure.

Normal role: Carnitine supports hepatic long-chain fatty-acid use.

Recorded consequence: Serum free carnitine falls; two of six subjects have impaired ketogenesis during fasting.

Scope: Six healthy men in a before-and-after drug/fasting study.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Choline: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Carnitine-derived TMAO and mouse atherosclerosis: adverse versus inverse relationshipsA carnitine/microbiota intervention increased lesions in one mouse study, whereas a later hCETP-expressing ApoE-null model found higher TMAO associated with smaller lesions. The papers support opposing interpretations of a universal proatherogenic TMAO relationship, but the second result is a correlation in a different model.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

L-Carnitine

The mechanisms

Expressing human ALDH9 in bacteria produced NAD+-dependent trimethylaminobutyraldehyde dehydrogenase activity, completing the aldehyde-to-gamma-butyrobetaine step.

Human tissue assays detected gamma-butyrobetaine-to-carnitine activity in liver, kidney and brain, but not heart or skeletal muscle; the earlier steps were detected in all five tissues.

Single oral L-carnitine doses had estimated bioavailability of 16% at 2 g and 5% at 6 g, with similar plasma exposure despite the higher dose.

Human OCTN2 transport measurements were consistent with approximately one sodium ion accompanying each carnitine molecule.

Expressed human OCTN2 transported acetyl-L-carnitine in a sodium-dependent manner with a measured Km of 8.5 micromolar.

Human OCTN2 transported D-carnitine with lower affinity than L-carnitine: reported Km values were 10.9 versus 4.3 micromolar.

Fibroblasts carrying truncating OCTN2 variants from two unrelated patients lacked mediated carnitine transport.

Transfecting patient fibroblasts with normal OCTN2 cDNA partially restored carnitine transport.

In a reported patient with homozygous SLC22A5-associated primary carnitine deficiency and a cardiac presentation, cardiac function remained normal during 14 years of oral carnitine treatment.

Human CPT1B expressed in yeast catalyzed transfer from palmitoyl-CoA onto carnitine, forming palmitoylcarnitine and releasing CoA.

Purified rat mitochondrial CACT reconstituted into liposomes exchanged carnitine and transported acylcarnitines of several chain lengths.

Expressed human CPT2 formed medium- and long-chain acylcarnitines from acyl-CoAs; its physiological matrix-side reaction reconverts incoming acylcarnitines to acyl-CoAs plus free carnitine.

Human CPT2 had activity with C8-C18 acyl-CoAs but virtually none with short-chain acyl-CoAs or branched-chain amino-acid oxidation intermediates.

The human SLC25A20 p.Arg133Trp substitution impaired carrier activity after bacterial expression and liposome reconstitution.

Myocytes derived from a CPT2-deficient patient accumulated palmitoylcarnitine; incubation at 38 degrees C accentuated accumulation relative to control myocytes.

Copper inhibited rat-liver CACT carnitine exchange in proteoliposomes, with a native-protein IC50 of 1.6 micromolar.

Adding reduced glutathione reversed copper inhibition of the reconstituted native rat carnitine-acylcarnitine carrier.

Muscle Crat deletion reduced short-chain acyltransferase activity and acetylcarnitine pools, supporting transfer of acetyl groups from acetyl-CoA to carnitine.

Adding carnitine stimulated PDH activity 1.8-fold in control muscle mitochondria but did not stimulate it in Crat-null mitochondria.

Silencing CRAT in primary human myotubes reduced acetylcarnitine export by 47%.

Silencing CRAT in human myotubes reduced glucose uptake by 13% while increasing oleate oxidation.

Twice-daily carnitine tartrate plus carbohydrate for 24 weeks increased muscle total carnitine by 21%; carbohydrate-only controls did not show loading.

After the loading regimen, muscle glycogen use at 50% exercise intensity was 55% lower than in carbohydrate-only controls.

At 80% exercise intensity after loading, muscle PDC activation was 38% higher and lactate was lower than in controls.

Isotope-labeled acetylcarnitine supplied acetyl-CoA and fatty-acid carbon in glucose-limited human U87MG glioma cells.

Deleting CROT reduced labeling of acetyl-CoA and palmitate from exogenous acetylcarnitine; CROT cDNA rescue restored acetyl-CoA labeling.

Deleting CRAT did not diminish acetyl-CoA labeling from supplied acetylcarnitine in U87MG cells.

Adding acetylcarnitine increased histone acetylation in lipid-depleted mouse HCC cells lacking both ACLY and ACSS2.

Removing Crat impaired glucose-derived lipid synthesis in ACLY-deficient mouse HCC cells.

Giving L-carnitine to three patients with propionic acidemia increased urinary propionylcarnitine, verified by mass spectrometry.

Four patients with propionic or methylmalonic aciduria had low plasma free carnitine and elevated short-chain acylcarnitine excretion; muscle carnitine was low in two biopsied patients.

Twelve days of pivmecillinam reduced mean serum free carnitine from 42.8 to 11.6 micromolar, while measured muscle carnitine was unchanged.

After pivmecillinam-associated carnitine depletion, two of six subjects showed impaired ketone production during a 36-hour fast.

In the patient observed when starting valproate, plasma carnitine fell during weeks 1-3 and recovered by weeks 3-5.

Valproylcarnitine fractional renal excretion approached 100%, unlike the strongly reabsorbed free carnitine pool; transporter assays showed low OCTN2 affinity.

Adding 10 mM carnitine reduced nuclear T3 uptake in human HepG2 cells by about 35%; 50 mM produced a larger reduction.

In a six-month trial of 50 women on fixed TSH-suppressive thyroxine, 2 or 4 g/day carnitine reduced or limited several hyperthyroid symptoms during treatment periods.

Acetyl-L-carnitine treatment increased Grm2-associated H3K27 acetylation and mGlu2 expression in Flinders Sensitive Line rats.

Acetyl-L-carnitine did not produce the reported behavioral benefit in mGlu2-knockout mice exposed to chronic unpredictable stress.

In a 409-patient randomized trial during adjuvant taxane chemotherapy, acetyl-L-carnitine did not significantly improve the primary 12-week neuropathy endpoint.

At 24 weeks in the same taxane trial, the acetyl-L-carnitine arm had worse neuropathy scores and more severe neurotoxicity than placebo.

Human tracer, fecal culture and antibiotic studies supported microbial conversion of carnitine to gamma-butyrobetaine, occurring rapidly in both dietary groups.

Chronic carnitine exposure increased microbial gamma-butyrobetaine-to-TMA conversion; baseline labeled TMAO generation was greater in omnivores.

Adding E. timonensis in coculture completed the carnitine-to-TMA conversion using other microbes' gamma-butyrobetaine production.

Purified BbuB and BbuC together transferred CoA onto gamma-butyrobetaine; neither component alone reproduced the tested activity.

BbuA converted gamma-butyrobetainyl-CoA to TMA and crotonyl-CoA in the reconstituted anaerobic pathway.

Acinetobacter baumannii CntA/CntB catalyzed oxygen-dependent carnitine cleavage to TMA and malic semialdehyde.

CntB passed NADH-derived electrons through FMN and iron-sulfur centers to support CntA oxygen activation.

Adding E. timonensis to defined microbial communities in gnotobiotic mice completed carnitine-to-TMA conversion, raised TMAO and enhanced thrombosis after arterial injury.

Chronic dietary carnitine increased atherosclerosis in the studied mice; concurrent microbial suppression prevented that increase.

In male ApoE-null mice expressing human CETP, carnitine raised TMAO but higher TMAO correlated with smaller aortic lesions across treatment groups.

Two grams/day carnitine for six months did not significantly change the primary total-carotid-plaque-volume outcome versus placebo.

The carnitine arm in the same trial had greater progression of carotid stenosis than placebo, reported as a 9.3% difference; total and LDL cholesterol also increased.

Genetic loss of Cpt1a or Cpt2 did not reproduce the strong block of IL-4-driven macrophage polarization caused by high-dose etomoxir.

High etomoxir exposure depleted free CoA and inhibited IL-4 macrophage polarization even without Cpt1a or Cpt2 expression.

T-cell-specific Cpt1a deletion showed that the ACC2/Cpt1a pathway was largely dispensable for memory and regulatory T-cell formation in the tested models.

Expressing mouse ATB0,+ in HRPE cells enabled carnitine transport requiring both sodium and chloride; activation analysis was consistent with two sodium ions and one chloride ion.

Amino-acid substrates inhibited carnitine transport through expressed mouse ATB0,+.

Human CT2 expressed in Xenopus oocytes mediated high-affinity carnitine transport; tissue staining located CT2 in epididymal luminal membranes and Sertoli cells.

Human OCTN2 cryo-EM structures identified a sodium-binding cavity separate from the carnitine site, with allosteric coupling supported by electrophysiology.

Purified recombinant human CRAT transferred short-chain acyl groups including acetyl from acyl-CoA substrates to carnitine in enzyme assays.

Adding palmitoylcarnitine impaired mitochondrial membrane potential and spare respiratory capacity in leukocytes from healthy donors.

Palmitoylcarnitine exposure increased CXCL8 expression and IL-8 release in human donor leukocytes.

Albumin reduced palmitoylcarnitine-associated oxidative stress and membrane-potential impairment in donor leukocytes.

Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis.

Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.

Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine.

Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1.

BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron.

Omission controls with recombinant human MBP-TMLH-a showed that ascorbate, Fe(II) and 2-oxoglutarate were each needed for efficient conversion of free trimethyllysine to 3-hydroxytrimethyllysine.

Increasing ascorbate supplementation increased carnitine accumulation from gamma-butyrobetaine in primary guinea-pig hepatocytes after four hours.

Gamma-butyrobetaine supplementation lowered both reduced and total cellular vitamin C content during the guinea-pig hepatocyte carnitine-synthesis experiment.

Guinea pigs with tissue vitamin C around 12% saturation had significantly lower muscle carnitine than animals near 100% saturation, without the customary overt hypovitaminosis-C signs in this experiment.

Oral trimethyllysine increased urine-based estimated carnitine synthesis by 32–40 micromol/kg/day across ascorbate-replete, deficient and pair-fed guinea-pig groups; vitamin C deficiency did not abolish the precursor response.

Oral gamma-butyrobetaine increased urine-based estimated carnitine synthesis by 41–50 micromol/kg/day across ascorbate-replete, deficient and pair-fed guinea-pig groups; vitamin C deficiency did not abolish the precursor response.

Without carnitine-precursor supplements, vitamin-C-deficient guinea pigs excreted approximately three times as much free and total carnitine as replete animals on days 19–28; pair feeding alone did not produce that pattern.

Palmitoylcarnitine antagonized acetyl-CoA inhibition of human PANK2, providing a positive regulatory input in biochemical assays.

Free carnitine did not activate purified human PANK2 in the experiment shown in Fig. 4B.