Component

1-Deoxysphingolipids

Context-specific entity; species, compartment and exposure are stated on each claim.

11 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Deoxysphingolipid exposure caused photoreceptor-cell death in human retinal organoids, which was prevented by tested regulators of lipid metabolism.

    1-Deoxysphingolipids → Photoreceptor survival in human retinal organoids source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human retinal organoid exposure experiment.
    limitations
    The result does not establish effective serine treatment for people with MacTel.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    The abnormal lipid can itself damage cells in an experimental retinal model.
    primary_references
    Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 286–292

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human retinal organoid exposure experiment. · source_derived_draft · unverified_draft

    ## l-serine-organoid-lipid-toxicity The abnormal lipid can itself damage cells in an experimental retinal model. Deoxysphingolipid exposure caused photoreceptor-cell death in human retinal organoids, which was prevented by tested regulators of lipid metabolism. Model: Human retinal organoid exposure experiment. Limitations: The result does not establish effective serine treatment for people with MacTel. Evidence access: Primary abstract Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
    Complete structured claim and evidence

What acts on it

  1. Targeting mitochondrial pyruvate transport promoted alanine oxidation, reduced deoxysphingolipid production and restored growth under serine/glycine-restricted conditions.

    Mitochondrial pyruvate carrier targeting in colorectal cancer models → 1-Deoxysphingolipids source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Colorectal cancer model metabolic interventions and tracing.
    limitations
    Context-specific rerouting; it does not establish a universal protective effect of MPC inhibition.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    Changing use of alanine in mitochondria changed its availability to another pathway.
    primary_references
    Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 464–470

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Colorectal cancer model metabolic interventions and tracing. · source_derived_draft · unverified_draft

    ## alanine-serine-mpc-interaction Changing use of alanine in mitochondria changed its availability to another pathway. Targeting mitochondrial pyruvate transport promoted alanine oxidation, reduced deoxysphingolipid production and restored growth under serine/glycine-restricted conditions. Model: Colorectal cancer model metabolic interventions and tracing. Limitations: Context-specific rerouting; it does not establish a universal protective effect of MPC inhibition. Evidence access: Primary full text Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
    Complete structured claim and evidence

  2. Serine/glycine restriction increased alanine-derived deoxysphingolipid synthesis in the tested colorectal cancer models and constrained growth.

    Serine/glycine restriction in human colorectal cancer models → 1-Deoxysphingolipids source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts.
    limitations
    Cancer nutrient-restriction experiments are not a recommendation to restrict serine or glycine.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    The ratio of available substrates can redirect a shared enzyme even without the inherited neuropathy setting.
    primary_references
    Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 456–462

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts. · source_derived_draft · unverified_draft

    ## alanine-serine-restriction-lipids The ratio of available substrates can redirect a shared enzyme even without the inherited neuropathy setting. Serine/glycine restriction increased alanine-derived deoxysphingolipid synthesis in the tested colorectal cancer models and constrained growth. Model: Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts. Limitations: Cancer nutrient-restriction experiments are not a recommendation to restrict serine or glycine. Evidence access: Primary full text Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
    Complete structured claim and evidence

  3. A pilot study in 14 HSAN1 patients found reduced deoxysphingolipid levels during oral serine supplementation.

    L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Small human HSAN1 serine-supplementation pilot.
    limitations
    Biomarker lowering alone does not establish neurological recovery, and the intervention was serine rather than alanine.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    The human pilot measured a biochemical response.
    primary_references
    Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 448–454

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small human HSAN1 serine-supplementation pilot. · source_derived_draft · unverified_draft

    ## alanine-spt-human-serine The human pilot measured a biochemical response. A pilot study in 14 HSAN1 patients found reduced deoxysphingolipid levels during oral serine supplementation. Model: Small human HSAN1 serine-supplementation pilot. Limitations: Biomarker lowering alone does not establish neurological recovery, and the intervention was serine rather than alanine. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
    Complete structured claim and evidence

  4. A 10% alanine-enriched diet increased deoxysphingolipids and led to severe peripheral neuropathy in mice expressing the HSAN1-associated C133W SPTLC1 transgene.

    L-Alanine → 1-Deoxysphingolipids source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Transgenic HSAN1 mouse model; 10% enriched diet.
    limitations
    High-dose disease model, not a toxicity threshold for ordinary human alanine intake.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    High alanine exposure worsened a specific genetically altered pathway.
    primary_references
    Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 432–438

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transgenic HSAN1 mouse model; 10% enriched diet. · source_derived_draft · unverified_draft

    ## alanine-spt-mouse-alanine High alanine exposure worsened a specific genetically altered pathway. A 10% alanine-enriched diet increased deoxysphingolipids and led to severe peripheral neuropathy in mice expressing the HSAN1-associated C133W SPTLC1 transgene. Model: Transgenic HSAN1 mouse model; 10% enriched diet. Limitations: High-dose disease model, not a toxicity threshold for ordinary human alanine intake. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
    Complete structured claim and evidence

  5. Human SPTLC1 mutant expression in HEK cells shifted substrate use toward alanine and increased production of deoxysphingolipids; amino-acid availability modulated this production.

    Human HSAN1-associated SPTLC1 variants → 1-Deoxysphingolipids source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human SPTLC1 variants expressed in HEK cells.
    limitations
    Variant-dependent abnormal chemistry is not a universal response to alanine intake.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    An enzyme can make different lipids when its substrate preference changes.
    primary_references
    Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 424–430

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SPTLC1 variants expressed in HEK cells. · source_derived_draft · unverified_draft

    ## alanine-spt-mutant-substrate An enzyme can make different lipids when its substrate preference changes. Human SPTLC1 mutant expression in HEK cells shifted substrate use toward alanine and increased production of deoxysphingolipids; amino-acid availability modulated this production. Model: Human SPTLC1 variants expressed in HEK cells. Limitations: Variant-dependent abnormal chemistry is not a universal response to alanine intake. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
    Complete structured claim and evidence

  6. A 10% serine-enriched diet reduced deoxysphingolipids and improved selected motor and sensory outcomes in C133W SPTLC1 transgenic mice.

    L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    HSAN1 transgenic mouse dietary intervention.
    limitations
    Mouse neurological outcomes do not establish human clinical benefit.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    Restoring the competing normal substrate changed the abnormal lipid output.
    primary_references
    Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 440–446

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HSAN1 transgenic mouse dietary intervention. · source_derived_draft · unverified_draft

    ## alanine-spt-serine-rescue Restoring the competing normal substrate changed the abnormal lipid output. A 10% serine-enriched diet reduced deoxysphingolipids and improved selected motor and sensory outcomes in C133W SPTLC1 transgenic mice. Model: HSAN1 transgenic mouse dietary intervention. Limitations: Mouse neurological outcomes do not establish human clinical benefit. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
    Complete structured claim and evidence

  7. In the randomized HSAN1 trial, oral L-serine reduced deoxysphinganine by 59% versus an 11% increase with placebo after one year.

    L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    18 randomized adults; 16 completed; 400 mg/kg/day versus placebo for one year followed by open-label treatment.
    limitations
    High-dose disease-specific research regimen, not a general supplement recommendation.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Changing substrate supply changed the abnormal lipid product in this inherited disorder.
    primary_references
    Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30626650/ · DOI 10.1212/WNL.0000000000006811

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 294–300

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 18 randomized adults; 16 completed; 400 mg/kg/day versus placebo for one year followed by open-label treatment. · source_derived_draft · unverified_draft

    ## l-serine-hsan-trial-lipids Changing substrate supply changed the abnormal lipid product in this inherited disorder. In the randomized HSAN1 trial, oral L-serine reduced deoxysphinganine by 59% versus an 11% increase with placebo after one year. Model: 18 randomized adults; 16 completed; 400 mg/kg/day versus placebo for one year followed by open-label treatment. Limitations: High-dose disease-specific research regimen, not a general supplement recommendation. Evidence access: Primary abstract Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30626650/ · DOI 10.1212/WNL.0000000000006811
    Complete structured claim and evidence

  8. Among 125 MacTel type 2 patients without pathogenic SPT variants and 94 controls, circulating serine was lower and deoxysphingolipids higher in the patient group.

    L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human case-control metabolomics; serine 20.6% lower and deoxysphingolipids 84.2% higher.
    limitations
    Association does not establish a dietary cause, universal threshold or supplementation benefit.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    A low measured amino-acid pool was associated with an abnormal lipid signature.
    primary_references
    Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 270–276

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human case-control metabolomics; serine 20.6% lower and deoxysphingolipids 84.2% higher. · source_derived_draft · unverified_draft

    ## l-serine-mac-tel-association A low measured amino-acid pool was associated with an abnormal lipid signature. Among 125 MacTel type 2 patients without pathogenic SPT variants and 94 controls, circulating serine was lower and deoxysphingolipids higher in the patient group. Model: Human case-control metabolomics; serine 20.6% lower and deoxysphingolipids 84.2% higher. Limitations: Association does not establish a dietary cause, universal threshold or supplementation benefit. Evidence access: Primary abstract Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Experimentally lowering serine in mice increased retinal deoxysphingolipids and compromised visual function.

    L-Serine → Retinal deoxysphingolipid accumulation in low-serine mice source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse low-serine model in the MacTel study.
    limitations
    Mouse manipulation is distinct from the observational human plasma comparison.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Reduced availability can change the products of lipid synthesis.
    primary_references
    Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 278–284

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse low-serine model in the MacTel study. · source_derived_draft · unverified_draft

    ## l-serine-mouse-low-serine-retina Reduced availability can change the products of lipid synthesis. Experimentally lowering serine in mice increased retinal deoxysphingolipids and compromised visual function. Model: Mouse low-serine model in the MacTel study. Limitations: Mouse manipulation is distinct from the observational human plasma comparison. Evidence access: Primary abstract Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
    Complete structured claim and evidence

  2. Limiting serine in cells expressing SPTLC1-ALS variants increased deoxysphingolipids and shifted the lipid profile toward an HSAN1-like signature.

    L-Serine → Substrate-dependent lipid signature in human SPTLC1-ALS models source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context.
    limitations
    Neither unrestricted supplementation nor restriction is shown to be a universal remedy.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Restricting substrate can trade one abnormal lipid pattern for another.
    primary_references
    SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35900868/ · DOI 10.1172/JCI161908
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 326–332

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context. · source_derived_draft · unverified_draft

    ## l-serine-spt-low-serine-switch Restricting substrate can trade one abnormal lipid pattern for another. Limiting serine in cells expressing SPTLC1-ALS variants increased deoxysphingolipids and shifted the lipid profile toward an HSAN1-like signature. Model: Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context. Limitations: Neither unrestricted supplementation nor restriction is shown to be a universal remedy. Evidence access: Primary abstract SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35900868/ · DOI 10.1172/JCI161908
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards