Component

Human serine palmitoyltransferase long-chain base subunit 1

Human serine palmitoyltransferase long-chain base subunit 1

7 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. Four dominantly acting SPTLC1 variants in childhood-onset ALS families disrupted ORMDL-mediated feedback, increasing canonical sphingolipid synthesis.

    Human serine palmitoyltransferase long-chain base subunit 1 → ORMDL restraint of human serine palmitoyltransferase source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human families and engineered cellular lipid-synthesis experiments.
    limitations
    This molecular subtype differs from HSAN1-associated substrate-switching variants.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Some variants remove the brake rather than change the preferred amino-acid substrate.
    primary_references
    Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34059824/ · DOI 10.1038/s41591-021-01346-1
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 310–316

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human families and engineered cellular lipid-synthesis experiments. · source_derived_draft · unverified_draft

    ## l-serine-als-spt-feedback Some variants remove the brake rather than change the preferred amino-acid substrate. Four dominantly acting SPTLC1 variants in childhood-onset ALS families disrupted ORMDL-mediated feedback, increasing canonical sphingolipid synthesis. Model: Human families and engineered cellular lipid-synthesis experiments. Limitations: This molecular subtype differs from HSAN1-associated substrate-switching variants. Evidence access: Primary abstract Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34059824/ · DOI 10.1038/s41591-021-01346-1
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. 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

  2. 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

  3. 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

  4. 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

  5. Human SPT structures place PLP at the SPTLC1-SPTLC2 interface, with the catalytic lysine supplied by SPTLC2.

    PLP → Human serine palmitoyltransferase long-chain base subunit 2 source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays
    exposure
    Cryo-EM of recombinant complexes.
    limitations
    No dietary B6 manipulation.
    nutrient_topic
    Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
    organism
    Homo sapiens
    plain_language
    SPT uses activated B6 where its two core subunits meet.
    primary_references
    [wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1108–1118

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays · source_derived_draft · unverified_draft

    ### b6-neuro-spt-plp-site Human SPT structures place PLP at the SPTLC1-SPTLC2 interface, with the catalytic lysine supplied by SPTLC2. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: SPT uses activated B6 where its two core subunits meet. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays limitations: No dietary B6 manipulation. exposure: Cryo-EM of recombinant complexes. [wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
    Complete structured claim and evidence

  6. 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.

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