Component

Human citrin / SLC25A13

Human citrin / SLC25A13. Species, exposure and limitations are retained in each linked claim.

8 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. Reconstituted citrin exchanged aspartate for glutamate plus a proton.

    Human citrin / SLC25A13 → Mitochondrial aspartate/glutamate exchange source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"}
    experimental_model
    Reconstituted transporter and transfected-cell assays
    exposure
    Aspartate exchange for glutamate plus proton; external calcium stimulation
    limitations
    Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human citrin and aralar proteins
    plain_language
    Moving aspartate between compartments helps connect nitrogen handling and redox metabolism.
    primary_references
    [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
    tissue_or_cell_type
    Inner mitochondrial membrane transport; malate-aspartate shuttle

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 359–370

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted transporter and transfected-cell assays · source_derived_draft · unverified_draft

    ### citrulline-citrin-aspartate Reconstituted citrin exchanged aspartate for glutamate plus a proton. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Moving aspartate between compartments helps connect nitrogen handling and redox metabolism. organism: Human citrin and aralar proteins tissue_or_cell_type: Inner mitochondrial membrane transport; malate-aspartate shuttle experimental_model: Reconstituted transporter and transfected-cell assays limitations: Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency. exposure: Aspartate exchange for glutamate plus proton; external calcium stimulation evidence_span: {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"} [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
    Complete structured claim and evidence

  2. Citrin overexpression increased malate-aspartate shuttle activity in transfected human cells.

    Human citrin / SLC25A13 → Malate-aspartate shuttle activity source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"}
    experimental_model
    Reconstituted transporter and transfected-cell assays
    exposure
    Aspartate exchange for glutamate plus proton; external calcium stimulation
    limitations
    Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human citrin and aralar proteins
    plain_language
    The same transporter participates in moving reducing equivalents between compartments.
    primary_references
    [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
    tissue_or_cell_type
    Inner mitochondrial membrane transport; malate-aspartate shuttle

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 385–396

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted transporter and transfected-cell assays · source_derived_draft · unverified_draft

    ### citrulline-citrin-shuttle Citrin overexpression increased malate-aspartate shuttle activity in transfected human cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same transporter participates in moving reducing equivalents between compartments. organism: Human citrin and aralar proteins tissue_or_cell_type: Inner mitochondrial membrane transport; malate-aspartate shuttle experimental_model: Reconstituted transporter and transfected-cell assays limitations: Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency. exposure: Aspartate exchange for glutamate plus proton; external calcium stimulation evidence_span: {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"} [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
    Complete structured claim and evidence

What acts on it

  1. Calcium on the external side of the inner mitochondrial membrane stimulated citrin-mediated exchange.

    Calcium ion → Human citrin / SLC25A13 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"}
    experimental_model
    Reconstituted transporter and transfected-cell assays
    exposure
    Aspartate exchange for glutamate plus proton; external calcium stimulation
    limitations
    Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human citrin and aralar proteins
    plain_language
    Calcium is a regulatory signal for the transporter.
    primary_references
    [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
    tissue_or_cell_type
    Inner mitochondrial membrane transport; malate-aspartate shuttle

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 372–383

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted transporter and transfected-cell assays · source_derived_draft · unverified_draft

    ### citrulline-citrin-calcium Calcium on the external side of the inner mitochondrial membrane stimulated citrin-mediated exchange. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium is a regulatory signal for the transporter. organism: Human citrin and aralar proteins tissue_or_cell_type: Inner mitochondrial membrane transport; malate-aspartate shuttle experimental_model: Reconstituted transporter and transfected-cell assays limitations: Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency. exposure: Aspartate exchange for glutamate plus proton; external calcium stimulation evidence_span: {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"} [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
    Complete structured claim and evidence

  2. Human citrin regulatory-domain structures resolved calcium at EF-hand 2; the other EF-hand motifs were not all calcium-binding sites.

    Calcium ion → Human citrin / SLC25A13 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human SLC25A13 regulatory-domain crystallography; calcium-bound and calcium-free structures.
    limitations
    Domain structures do not define a dietary calcium threshold or a treatment for citrin deficiency.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Several similarly named structural motifs do not mean several equivalent calcium switches.
    primary_references
    Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 98–104

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SLC25A13 regulatory-domain crystallography; calcium-bound and calcium-free structures. · source_derived_draft · unverified_draft

    ## l-aspartate-citrin-calcium-site Several similarly named structural motifs do not mean several equivalent calcium switches. Human citrin regulatory-domain structures resolved calcium at EF-hand 2; the other EF-hand motifs were not all calcium-binding sites. Model: Human SLC25A13 regulatory-domain crystallography; calcium-bound and calcium-free structures. Limitations: Domain structures do not define a dietary calcium threshold or a treatment for citrin deficiency. Evidence access: Primary full text Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. ASS1-deficient citrullinemia type I models showed greater pyrimidine synthesis and proliferation than citrin-deficient type II models, where aspartate delivery was restricted.

    Comparison of ASS1 deficiency and citrin deficiency → Pyrimidine synthesis in citrullinemia study models source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human disorder-derived observations and experimental disease/cancer comparisons.
    limitations
    Neither condition is simple low dietary aspartate; do not turn cellular proliferation measures into patient cancer-risk estimates.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Two defects affecting the same cycle can leave very different amounts of substrate for another pathway.
    primary_references
    Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 178–184

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human disorder-derived observations and experimental disease/cancer comparisons. · source_derived_draft · unverified_draft

    ## l-aspartate-ass1-citrin-difference Two defects affecting the same cycle can leave very different amounts of substrate for another pathway. ASS1-deficient citrullinemia type I models showed greater pyrimidine synthesis and proliferation than citrin-deficient type II models, where aspartate delivery was restricted. Model: Human disorder-derived observations and experimental disease/cancer comparisons. Limitations: Neither condition is simple low dietary aspartate; do not turn cellular proliferation measures into patient cancer-risk estimates. Evidence access: Primary abstract Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
    Complete structured claim and evidence

  2. Absolute proteomics found citrin/aralar molar ratios of about 7.8 in mouse liver and 397 in human liver, indicating much less endogenous aralar relative to citrin in humans.

    Species-dependent liver aspartate-carrier expression → Human aralar / SLC25A12 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse and human liver quantitative proteomics.
    limitations
    Sampled expression ratios are not universal constants or proof of a clinical rescue strategy.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    A mouse may compensate for a missing carrier more readily than a human.
    primary_references
    Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 138–144

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse and human liver quantitative proteomics. · source_derived_draft · unverified_draft

    ## l-aspartate-carrier-species-expression A mouse may compensate for a missing carrier more readily than a human. Absolute proteomics found citrin/aralar molar ratios of about 7.8 in mouse liver and 397 in human liver, indicating much less endogenous aralar relative to citrin in humans. Model: Mouse and human liver quantitative proteomics. Limitations: Sampled expression ratios are not universal constants or proof of a clinical rescue strategy. Evidence access: Primary full text Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967
    Complete structured claim and evidence

  3. Calcium-associated movement of the mobile regulatory domain opened a vestibule in regulatory-domain structures; the authors proposed that this controls substrate access.

    Calcium ion → Regulatory vestibule of human aspartate/glutamate carriers source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human citrin/aralar domain structures and structural model.
    limitations
    The substrate-access gating mechanism is structure-supported interpretation, not direct observation of an entire transport cycle.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Calcium binding can change access to the transport machinery.
    primary_references
    Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 114–120

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human citrin/aralar domain structures and structural model. · source_derived_draft · unverified_draft

    ## l-aspartate-carrier-vestibule Calcium binding can change access to the transport machinery. Calcium-associated movement of the mobile regulatory domain opened a vestibule in regulatory-domain structures; the authors proposed that this controls substrate access. Model: Human citrin/aralar domain structures and structural model. Limitations: The substrate-access gating mechanism is structure-supported interpretation, not direct observation of an entire transport cycle. Evidence access: Primary full text Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491
    Complete structured claim and evidence

  4. Loss of shuttle components reduced pyruvate/lactate ratios and glucose-derived serine synthesis in the studied human A549 models.

    Genetic loss of shuttle components in human A549 cells → Glucose-derived serine synthesis in human A549 cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract and primary figure descriptions
    experimental_model
    Human lung-cancer cell gene editing, metabolite ratios and carbon tracing.
    limitations
    A ratio is a redox proxy, and no dietary serine/aspartate deficiency threshold was measured.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Redox handling connects aspartate machinery to synthesis of another amino acid.
    primary_references
    Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 234–240

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung-cancer cell gene editing, metabolite ratios and carbon tracing. · source_derived_draft · unverified_draft

    ## l-aspartate-shuttle-serine-link Redox handling connects aspartate machinery to synthesis of another amino acid. Loss of shuttle components reduced pyruvate/lactate ratios and glucose-derived serine synthesis in the studied human A549 models. Model: Human lung-cancer cell gene editing, metabolite ratios and carbon tracing. Limitations: A ratio is a redox proxy, and no dietary serine/aspartate deficiency threshold was measured. Evidence access: Primary abstract and primary figure descriptions Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004
    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