The AtlasAmino acidsNegatively charged
AspartateAsp · D
The shortest acidic amino acid: a carrier of electrons into mitochondria, of nitrogen into urea, and the metabolite growing cells breathe to make.
Molecule · Asp · 9 heavy atoms
Aspartate
C4H7NO4133.10 g/mol
The shortest acidic amino acid: a carrier of electrons into mitochondria, of nitrogen into urea, and the metabolite growing cells breathe to make.
Built fromthe charted ones open their own entry
- Codes
- Asp · D
- Formula
- C4H7NO4
- Molar mass
- 133.10 g/mol
- Systematic name
- (2S)-2-aminobutanedioic acid
- Side chain
- Carboxymethyl: one carbon and a carboxylic acid; negatively charged at the pH of blood.
- Class
- Negatively charged
- In the diet
- Dispensable
- Carbon skeleton
- Glucogenic
- pKa
- α-COOH 1.88 · α-NH3+ 9.60 · side chain 3.65
- Isoelectric point
- pH 2.77
- Hydropathy
- -3.5 (Kyte–Doolittle)
- Codons
GAUGAC- Main transporters
- SLC25A13 (citrin (AGC2)), SLC25A12 (aralar (AGC1)), SLC1A3 (EAAT1)
pKa and isoelectric point: Nelson and Cox, Lehninger Principles of Biochemistry, table of amino acid properties (free amino acid, 25 °C). Hydropathy: Kyte and Doolittle, J Mol Biol 1982. Essentiality: Reeds, J Nutr 2000. Formula and mass computed from the structure.
In brief
What it is
An amino acid whose side chain is a single carbon ending in a carboxylic acid, so it is negatively charged at the pH of blood. The body makes it from oxaloacetate, a Krebs cycle intermediate, by transamination 1,2.
Why it matters
It shuttles electrons from the cytoplasm into mitochondria in the malate–aspartate shuttle 1, and proliferating cells depend on making it: a main reason they need mitochondrial respiration at all is to supply aspartate 2,3. The enzyme that makes it, aspartate aminotransferase, is AST, one of the two liver enzymes on every routine blood test 4.
Where it runs short
Cells that cannot make aspartate stop dividing; supplying it, or a transporter to import it, lets cells with no working respiratory chain proliferate again 2,3. Some tumors in low oxygen are limited by aspartate 5.
Where it turns
Defects in the carriers that move aspartate out of mitochondria cause disease: citrin deficiency in the liver and AGC1 deficiency in the brain 6,7.
In the diet it does not matter. In a dividing cell it is one of the things oxygen is for.
The molecule
Aspartate is the shorter of the two acidic amino acids: a single carbon between the backbone and a carboxylic acid. Its side chain pKa is about 3.7, so at the pH of blood it is negatively charged.
In proteins, aspartate and asparagine residues slowly rearrange of their own accord into isoaspartate and D-aspartate, kinks that damage the protein. A dedicated enzyme repairs them; mice without it accumulated damaged proteins in brain, heart, liver and red cells, grew poorly and died of seizures at about six weeks 8.
A pKₐ that low makes the side chain a poor nucleophile, and that is part of why the commonest mutation in human cancer went undrugged for forty years. KRAS G12D puts exactly this carboxylate into the switch region of RAS, and carboxylic acids are both unreactive and everywhere else in the proteome. The answer was to stop relying on the chemistry: compounds that bind cyclophilin A create a neomorphic interface between cyclophilin A and active RAS, and that interface gives enzyme-like rate enhancement to the reaction between the D12 carboxylate and electrophilic warheads of exceptionally low intrinsic reactivity. The result is orally bioavailable, active across preclinical KRAS G12D models, and in clinical evaluation as zoldonrasib 9. Aspartate's least reactive feature is now a drug target in people.
Move across the chart to read the charge at any pH.
Computed from its pKa values (α-carboxyl 1.88, α-amino 9.60, side chain 3.65) by the Henderson–Hasselbalch equation, for the free amino acid in water at 25 °C. Inside a folded protein the same groups can shift by a unit or more. The faint lines are the other amino acids.
Kyte–Doolittle hydropathy index: positive values avoid water and tend to be buried inside a folded protein, negative values sit on its surface. Each letter is an amino acid; choose one to open it.
| 1st ↓ 2nd → | U | C | A | G | 3rd |
|---|---|---|---|---|---|
| U | UUUPhe | UCUSer | UAUTyr | UGUCys | U |
| UUCPhe | UCCSer | UACTyr | UGCCys | C | |
| UUALeu | UCASer | UAAStop | UGAStop | A | |
| UUGLeu | UCGSer | UAGStop | UGGTrp | G | |
| C | CUULeu | CCUPro | CAUHis | CGUArg | U |
| CUCLeu | CCCPro | CACHis | CGCArg | C | |
| CUALeu | CCAPro | CAAGln | CGAArg | A | |
| CUGLeu | CCGPro | CAGGln | CGGArg | G | |
| A | AUUIle | ACUThr | AAUAsn | AGUSer | U |
| AUCIle | ACCThr | AACAsn | AGCSer | C | |
| AUAIle | ACAThr | AAALys | AGAArg | A | |
| AUGMet | ACGThr | AAGLys | AGGArg | G | |
| G | GUUVal | GCUAla | GAUAsp | GGUGly | U |
| GUCVal | GCCAla | GACAsp | GGCGly | C | |
| GUAVal | GCAAla | GAAGlu | GGAGly | A | |
| GUGVal | GCGAla | GAGGlu | GGGGly | G |
Where it comes from
Every cell makes aspartate by transamination of oxaloacetate, in the mitochondria by GOT2 and in the cytoplasm by GOT1 2,10. Making oxaloacetate needs the electron acceptor NAD⁺, and regenerating NAD⁺ is what the respiratory chain does; that is the link that makes aspartate synthesis depend on oxygen 3.
DispensableMade from oxaloacetate in mitochondria and in the cytoplasm by the two aspartate aminotransferases, GOT2 and GOT1, so it is not needed in the diet 2,10.
How much
None; every cell makes it 2.
Where it is in food
- All protein. Aspartame contributes a small amount as it is digested 11.
In the bottle · enzymaticIndustrial L-aspartic acid was one of the first products of immobilized whole cells: Escherichia coli held in a gel, whose aspartase joins ammonia to fumarate, in columns that kept working with a half-life of about 120 days 12,13.
What the body does with it
The malate–aspartate shuttle, proposed in 1962 and later named for Piet Borst, is the main route by which liver and heart oxidize the NADH made in glycolysis. Its driving step is the export of aspartate from mitochondria in exchange for glutamate and a proton, powered by the respiratory chain 1.
Aspartate is a building block of nucleotides, and growing cells need it in quantity. When respiration fails, GOT1 reverses to make aspartate in the cytoplasm, and losing GOT1 kills cells whose respiration is blocked 2. In tumors, low oxygen lowers aspartate, and raising it, with an aspartate transporter, made tumors grow faster in mice 5.
In the urea cycle aspartate contributes the second nitrogen of urea, condensing with citrulline at argininosuccinate synthetase, the enzyme defective in citrullinemia type 1 14.
Which aspartate reaches the nucleotides turns out to be a question about compartments. In-cell isotope labeling (¹³C₆ glucose, ¹⁵N₂ glutamine) of the pyrimidinosome and the purinosome — the transient enzyme assemblies that build pyrimidines and purines — finds that the pool feeding the channelled pathway is mitochondrially generated and GOT2-dependent, not the bulk cytosolic pool and not GOT1; a low-flux diffusive route piles up the intermediates, and only the channelled one produces finished nucleotides 15. The transaminases themselves are also less load-bearing in a whole animal than the cell work implied: in pancreas-specific conditional knockout mice, losing either GOT1 or GOT2 left pancreas development, lesion formation, tumor size, survival and the tumor microenvironment unchanged, and only the double knockout shrank the pancreas — from the laboratory that originated much of this field, which notes that the earlier transplant studies had conflicted. That paper is a bioRxiv preprint and has not been peer-reviewed 16.
Aspartate also works outside the cell, as a signal rather than a brick. Lung interstitial fluid in patients and mice with breast cancer is high in aspartate, and that extracellular aspartate activates the ionotropic NMDA receptor on disseminated cancer cells, driving CREB-dependent expression of deoxyhypusine hydroxylase, hypusination of eIF5A, and a translational program hubbed on TGF-β that makes the cells synthesize collagen; the proteins of the mechanism are present in human lung metastases, which occur in up to 54% of patients with metastatic tumors 17. The mirror image is the more useful result for anyone thinking of taking it. Lowering aspartate, genetically or with aminooxyacetic acid, markedly amplifies cGAS–STING signaling: blocking pyrimidine synthesis downstream of aspartate stresses mitochondrial DNA replication, mitochondrial DNA reaches the cytosol, ZBP1 rises and IRF3 phosphorylation is sustained. In immunocompetent mice that made STING agonists, chemotherapy and radiotherapy work better, and supplementing aspartate abolished the benefit; in human colorectal cancer samples, aspartate correlated negatively with antitumor immunity 18.
And the carrier that drives the shuttle is not regulated the way its classification says. Citrin sits among the calcium-binding mitochondrial carriers, and its N-terminal EF-hand domain was taken to be the calcium switch on transport. Purified citrin reconstituted into proteoliposomes, tested against 33 pathogenic variants, says otherwise: the EF-hand domain is not involved in calcium regulation of transport at all, and mutating it causes a mitochondrial import defect instead 19.
One claimed role has been withdrawn outright. A 2025 Nature Microbiology paper described a cyclic aspartate–argininosuccinate shunt in macrophages, generating cytosolic fumarate through ASS1 and said to be required for interferon-β production and antiviral innate immunity. The journal retracted it in 2026, and PubMed now flags the original as a retracted publication; the notice carries no abstract and states no reason in the record 20. It is named here because a shunt that tidy gets drawn into reviews and stays there.
In three sentences each
Why proliferating cells breathe
Two 2015 studies found that a main job of the respiratory chain in dividing cells is to provide electron acceptors for making aspartate; giving aspartate, or pyruvate to regenerate those acceptors, rescued proliferation when respiration was blocked 2,3.
The malate–aspartate shuttle
NADH made in the cytoplasm cannot cross into mitochondria, so its electrons ride across on malate and come back out as aspartate; the export of aspartate, in exchange for glutamate and a proton, is what drives the cycle 1.
How it is made, moved and broken down
Aspartate and oxaloacetate interconvert in one step, so aspartate’s carbons are as available for making glucose as oxaloacetate’s 1. Its free D form, D-aspartate, is found in neuroendocrine tissue, where in rats it stimulates the release of LH and testosterone 21.
Carbon skeleton · glucogenicTransamination turns it straight back into oxaloacetate, the starting point of gluconeogenesis 1.
- Oxaloacetate + glutamate
- Aspartate aminotransferase (AST)GOT2 (mitochondria), GOT1 (cytoplasm) · vitamin B6
- Aspartate + 2-oxoglutarate
- Cytosolic NADH + oxaloacetate
- Malate dehydrogenase 1MDH1 · NADH
- Malate
- Malate dehydrogenase 2MDH2 · NAD⁺
- Oxaloacetate + NADH
- GOT2, then aspartate–glutamate carrierGOT2, SLC25A12/13 · vitamin B6
- Aspartate, exported
- Citrulline + aspartate
- Argininosuccinate synthetaseASS1 · ATP
- Argininosuccinate
How it crosses membranes
- SLC25A13 · citrin (AGC2)liver mitochondria — exports aspartate in exchange for glutamate; its loss causes citrin deficiency 6
- SLC25A12 · aralar (AGC1)neuron and muscle mitochondria — its loss causes a hypomyelinating encephalopathy 7
- SLC1A3 · EAAT1cell membranes — imports aspartate; in some cancer cells, the reason they tolerate blocked respiration 5
Where it matters most
- Brain
- Neuronal AGC1 supplies aspartate to the cytoplasm; without it myelin fails to form 7.
When it goes wrong
Inherited
Citrin deficiency
SLC25A13 · autosomal recessive
Three forms: neonatal intrahepatic cholestasis, which usually resolves with a lactose-free, medium-chain triglyceride formula by age one; a childhood phase of failure to thrive and abnormal lipids; and adult-onset type II citrullinemia, which in Japan affects about one person in 100,000 and can cause coma and fatal brain swelling 6,22,23. A diet low in carbohydrate and high in fat is expected to prevent progression 23. A nationwide Japanese study of 128 adults, carried out from 2022 to 2024, tempers that expectation. Former NICCD patients generally did well with early intervention and were taller than those with adolescent or adult onset (males 170.6 against 168.0 cm, p = 0.016; females 156.0 against 153.0 cm, p = 0.007), while the adult-onset group often had persistent or worsening symptoms, including irreversible liver damage with impaired urea cycle function 24. Early treatment looks protective; the adult-onset form, on guideline care, does not reliably hold.
How it is foundCitrulline on newborn screening, which misses some cases, then SLC25A13 sequencing 22,25.
Inherited
AGC1 deficiency
SLC25A12 · autosomal recessive
Arrested psychomotor development, low tone and seizures with global failure of myelination, from loss of the neuronal aspartate–glutamate carrier 7.
How it is foundBrain MRI and SLC25A12 sequencing 7.
Inherited
GOT2 deficiency
GOT2 · autosomal recessive
An early-infantile epileptic encephalopathy with low serine, high citrulline, lactate and ammonia; the seizures responded to serine and pyridoxine 10.
How it is foundMetabolic studies and exome sequencing 10.
Inherited
Citrullinemia type 1
ASS1 · autosomal recessive
The enzyme that joins aspartate to citrulline fails; presentations range from life-threatening neonatal hyperammonemia to mild late onset and purely biochemical cases 14.
How it is foundPlasma citrulline and ASS1 sequencing 14.
Biomarker
Macro-AST
A benign cause of a persistently raised AST, from the enzyme bound into a large complex that is cleared slowly; recognizing it spares patients repeated investigation 26,27.
How it is foundPolyethylene glycol precipitation 26.
Drug
L-ornithine L-aspartate
The one aspartate-containing drug in wide clinical use, given to lower ammonia in hepatic encephalopathy. In six randomized trials and 292 patients with cirrhosis and MINIMAL hepatic encephalopathy — the early, subclinical stage — it reversed the condition (RR 2.26, 95% CI 1.53 to 3.35, I² = 0%) and reduced progression to overt encephalopathy (RR 0.22, 95% CI 0.08 to 0.64). It did not lower ammonia (SMD 0.04, 95% CI −0.29 to 0.38) and did not reduce mortality. Oral dosing reached significance for reversal where intravenous did not 28. The benefit arrived without the mechanism the drug is sold on, which is a reason to keep measuring it rather than to stop using it.
How it is measured
Aspartate itself is part of the plasma amino acid panel, but the measurement that matters clinically is its enzyme, AST. The ACG guideline treats AST and ALT together as markers of liver cell injury 4, and their ratio carries information about the time course and stage of disease 29. Before acting on a high AST alone, hemolysis, muscle injury and macro-AST should be excluded 26,30.
For the carrier's own disease there is now a candidate blood marker, where before there was none. In 67 plasma samples from 29 children with citrin deficiency, FGF21 was highly elevated (adjusted p < 0.001) and tracked triglycerides (β 0.273), citrulline and threonine. The authors are explicit that longitudinal studies are still needed before it can be used to monitor disease status or treatment response 31.
- AST (aspartate aminotransferase)Measured with ALT as a liver test; raised in liver cell injury, and also released from muscle and red cells 4,30.The AST-to-ALT ratio, the De Ritis ratio, reflects the time course of injury, because AST has a shorter half-life than ALT, 18 against 36 hours; a high ratio predicts fibrosis and cirrhosis in chronic liver disease 29.Hemolysis in the tube raises AST strongly 30,32. Macro-AST, the enzyme bound to an antibody, keeps AST high for years without disease and is confirmed by polyethylene glycol precipitation 26,27. Assays without vitamin B6 added read low in deficient patients 29.
Food, supplements and the evidence
Establishedreplicated in people, for a named outcome
Uncertainsmall, short, mixed, surrogate or preclinical
- Aspartame and cancer: classed by IARC as possibly carcinogenic, while JECFA judged the epidemiology not convincing and left the acceptable daily intake unchanged 33,34. Since then: a 100,004-person cohort with a raised hazard ratio and no dose–response 35; the first study to measure sweeteners in urine instead of asking about them, which found no association with breast cancer 36; and a Mendelian randomization that found nothing 37.
Sold asthe claim on the label, against the evidence
- “D-aspartic acid boosts testosterone.” One short study in untrained men; in resistance-trained men no effect at 3 g a day and a fall at 6 g 21,38,39. The newest trial gave it with ubiquinol and zinc, so it cannot attribute anything to the D-aspartic acid 40.
- “Magnesium aspartate, because the aspartate carries it in better.” Mineral aspartates are how most people actually buy aspartate, and the one measured consequence runs the other way. In a crossover trial in 15 healthy adults, magnesium aspartate reduced the absorption of 1 mg of levothyroxine by 12% (geometric mean ratio 0.88, 95% CI 0.81 to 0.95, p = 0.002), cut Cₘₐₓ by 7% and delayed Tₘₐₓ by 17%, while magnesium citrate reduced the area under the curve non-significantly by 7% 41. Levothyroxine should be taken away from magnesium altogether; if they are taken together, the citrate is the better salt.
What is strange about it
Children with citrin deficiency, a defect of the liver’s aspartate carrier, choose for themselves a diet high in protein and fat and avoid carbohydrate from early infancy; in a Japanese survey, carbohydrate content was the strongest predictor of what they disliked 42. The treatment that guidelines recommend is much the same diet 23. There is now a mechanism for the aversion, and it reframes the diet as a signal rather than a preference: loss of SLC25A13 makes glycerol-3-phosphate accumulate, glycerol-3-phosphate activates ChREBP, ChREBP transcribes FGF21, and FGF21 acts in the brain to restrain the intake of sweets and of alcohol — while also switching on the lipogenic genes 43. The children are not so much choosing the diet as being told to.
Aspartame, the sweetener, is a methyl ester of aspartyl-phenylalanine 11. In 2023 the WHO’s cancer agency classed it as possibly carcinogenic to humans, group 2B, while the WHO’s food additives committee kept the acceptable daily intake at 40 mg/kg, calling the epidemiology not convincing 33,34. Three studies since have pulled in different directions. In 100,004 US adults in the Cancer Prevention Study-II Nutrition Cohort, with 21,356 verified cancers, consuming aspartame at least monthly carried a higher risk of all cancers combined (adjusted HR 1.13, 95% CI 1.08 to 1.18) and of obesity-related cancers (1.17, 1.09 to 1.26) — with no clear dose–response for any outcome, which the authors flag themselves 35. The first study to MEASURE the exposure rather than ask about it found nothing: urinary concentrations of six non-nutritive sweeteners in 988 women against 272 incident breast cancers gave no association for aspartame or for the total sweetener score (HR 1.09, 95% CI 0.80 to 1.48), and the single positive signal was sucralose in 38 premenopausal cases, which the authors call exploratory 36. And the first genetic attempt — Mendelian randomization on instruments for sweetener taste perception — found no compelling evidence that perceiving aspartame causes cancer at any site 37. A cohort that cannot find a dose–response, a urinary measurement that finds nothing and a genetic instrument that finds nothing do not add up to a settled hazard.
D-aspartate is sold to raise testosterone on the strength of a 12-day study in 23 untrained men 21; in trained men, 3 g a day did nothing over 28 days, and 6 g a day lowered testosterone 38,39. A 2025 randomized double-blind trial in idiopathic male infertility is the newest thing a seller can point to: 2,660 mg of D-aspartic acid WITH 200 mg of ubiquinol and 10 mg of zinc, against starch placebo, 24 men a side for three months, improving progressive sperm motility (p = 0.047) and total testosterone (p = 0.009) 40. It is a three-ingredient product in 48 analyzed men, and it cannot say which ingredient moved anything.
The one new aspartame mechanism that would matter has nothing to do with aspartate. In mice and in monkeys, 0.15% aspartame markedly raised insulin secretion, and bilateral subdiaphragmatic vagotomy abolished the rise — putting the effect on parasympathetic activation rather than on any metabolite. Continued feeding worsened atherosclerotic plaque in ApoE-deficient mice by an insulin-dependent route; an implanted slow-release insulin pump did the same; CX3CL1 was the most upregulated gene in insulin-stimulated arterial endothelium; and deleting Cx3cr1 in monocytes and macrophages abolished the effect completely 44. If this is what the cardiovascular epidemiology has been seeing, then the sweetener's aspartate and methanol moieties are beside the point, and the tongue is not.
Where it connects
In the Atlas
Topics on the map
On the map
A star in The rest of the amino acids, one of 6. Half of aspartame, and the nitrogen donor the urea cycle and every purine depend on. The sweetener argument and the biochemistry are not the same argument.
Sources
44 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.
- 1Borst P. The malate-aspartate shuttle (Borst cycle): how it started and developed into a major metabolic pathway.doi:10.1002/iub.2367 · PMID 32916028
A personal history; aspartate efflux drives the shuttle.
- 2Birsoy K, Wang T, Chen WW, et al. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis.doi:10.1016/j.cell.2015.07.016 · PMID 26232224
GOT1 reverses when respiration fails; aspartate rescues growth. Cell studies.
- 3Sullivan LB, Gui DY, Hosios AM, et al. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells.doi:10.1016/j.cell.2015.07.017 · PMID 26232225
Electron acceptors limit aspartate synthesis. Cell studies.
- 4Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries.doi:10.1038/ajg.2016.517 · PMID 27995906
How to interpret AST and ALT.
- 5Garcia-Bermudez J, Baudrier L, La K, et al. Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours.doi:10.1038/s41556-018-0118-z · PMID 29941933
SLC1A3 import; cell and mouse studies.
- 6Kobayashi K, Sinasac DS, Iijima M, et al. The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.doi:10.1038/9667 · PMID 10369257
SLC25A13; about 1 in 100,000 in Japan.
- 7Wibom R, Lasorsa FM, Töhönen V, et al. AGC1 deficiency associated with global cerebral hypomyelination.doi:10.1056/NEJMoa0900591 · PMID 19641205
One child; abolished carrier activity.
- 8Kim E, Lowenson JD, MacLaren DC, et al. Deficiency of a protein-repair enzyme results in the accumulation of altered proteins, retardation of growth, and fatal seizures in mice.doi:10.1073/pnas.94.12.6132 · PMID 9177182
Mice without the isoaspartate repair enzyme died at about 42 days.
- 9Weller C, Burnett GL, Jiang L, et al. A neomorphic protein interface catalyzes covalent inhibition of RAS G12D aspartic acid in tumors.doi:10.1126/science.ads0239 · PMID 40705880
One aspartate side chain, in the commonest RAS mutation, made reactive enough to hit.
- 10van Karnebeek CDM, Ramos RJ, Wen XY, et al. Bi-allelic GOT2 mutations cause a treatable malate-aspartate shuttle-related encephalopathy.doi:10.1016/j.ajhg.2019.07.015 · PMID 31422819
Four children; serine- and pyridoxine-responsive.
- 11Magnuson BA, Burdock GA, Doull J, et al. Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies.doi:10.1080/10408440701516184 · PMID 17828671
Structure and use levels against ADIs. Industry-funded review.
- 12Tosa T, Sato T, Mori T, et al. Basic studies for continuous production of L-aspartic acid by immobilized Escherichia coli cells.doi:10.1128/am.27.5.886-889.1974 · PMID 4598223
The immobilized-cell process.
- 13Sato T, Mori T, Tosa T, et al. Engineering analysis of continuous production of L-aspartic acid by immobilized Escherichia coli cells in fixed beds.doi:10.1002/bit.260171209 · PMID 1106792
Column half-life about 120 days.
- 14Diez-Fernandez C, Rüfenacht V, Häberle J. Mutations in the human argininosuccinate synthetase (ASS1) gene, impact on patients, common changes, and structural considerations.doi:10.1002/humu.23184 · PMID 28111830
137 mutations; spectrum of citrullinemia type 1.
- 15Pareek V, Benkovic S. Metabolic profiling reveals channeled de novo pyrimidine and purine biosynthesis fueled by mitochondrially generated aspartic acid in cancer cells.doi:10.1038/s41467-025-64013-w · PMID 41062501
In-cell isotope labeling of the nucleotide metabolons, and the compartment the aspartate comes from.
- 16Ugras J, Nelson N, Kerk SA, et al. Aspartate transaminases are dispensable for pancreatic development and pancreatic cancer progression.doi:10.64898/2025.12.17.694916 · PMID 41473313
A preprint, and labeled as one on this page. It is the autochthonous-mouse test of an idea the cell work made famous.
- 17Doglioni G, Fernández-García J, Igelmann S, et al. Aspartate signalling drives lung metastasis via alternative translation.doi:10.1038/s41586-024-08335-7 · PMID 39743589
Aspartate outside the cell, acting on a receptor. A different kind of role from anything else on this page.
- 18Liao Y, Wang H, Liu H, et al. Aspartate deficiency amplifies cGAS-STING signaling in antitumor immunity.doi:10.1172/JCI199716 · PMID 42222880
The one place where giving aspartate to a living animal made the treatment work less well.
- 19Tavoulari S, Lacabanne D, Pereira GC, et al. Distinct roles for the domains of the mitochondrial aspartate/glutamate carrier citrin in organellar localization and substrate transport.doi:10.1016/j.molmet.2024.102047 · PMID 39419476
Purified carrier in proteoliposomes, 33 pathogenic variants, and the calcium domain doing something else.
- 20Xia W, Mao Y, Xia Z, Cheng J, Jiang P. Retraction Note: Metabolic remodelling produces fumarate via the aspartate-argininosuccinate shunt in macrophages as an antiviral defence.doi:10.1038/s41564-026-02307-5 · PMID 41781464
A whole claimed pathway of innate immunity, withdrawn. The notice carries no abstract and gives no reason.
- 21Topo E, Soricelli A, D’Aniello A, et al. The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats.doi:10.1186/1477-7827-7-120 · PMID 19860889
23 men, 12 days; and rats.
- 22Inui A, Ko JS, Chongsrisawat V, et al. Update on the diagnosis and management of neonatal intrahepatic cholestasis caused by citrin deficiency: expert review on behalf of the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition.doi:10.1002/jpn3.12042 · PMID 38374571
Lactose-free MCT formula; most recover by age one.
- 23Kido J, Makris G, Santra S, et al. Clinical landscape of citrin deficiency: a global perspective on a multifaceted condition.doi:10.1002/jimd.12722 · PMID 38503330
Three forms; low-carbohydrate, high-fat diet with MCT.
- 24Kido J, Häberle J, Sugawara K, et al. The status of adult patients with citrin deficiency in Japan: a report from the nation-wide study.doi:10.1016/j.ymgme.2025.109221 · PMID 40840052
128 adults, the first nationwide follow-up, and the adult-onset form going the other way.
- 25Wang P, Hu L, Chen Y, et al. Enhancing newborn screening sensitivity and specificity for missed NICCD using selected amino acids and acylcarnitines.doi:10.1186/s13023-025-03532-7 · PMID 39799340
Screening misses some cases.
- 26Reddy N, Odish FS, Agrawal S. Macro-aspartate aminotransferase: a benign cause of abnormal laboratory findings.doi:10.7759/cureus.23841 · PMID 35530879
Case report.
- 27Arshad I, Zouridis S, Syn W. Macro-aspartate aminotransferase mimicking hepatic injury: a diagnostic dilemma for clinicians.doi:10.1136/bcr-2025-269789 · PMID 41839520
Case report.
- 28He Q, Mao C, Chen Z, Zeng Y, Deng Y, Hu R. Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: a meta-analysis of randomized controlled trials.doi:10.1016/j.ajg.2024.01.006 · PMID 38403493
Six trials, 292 patients. The benefit appeared; the ammonia did not move.
- 29Botros M, Sikaris KA. The De Ritis ratio: the test of time.PMID 24353357
AST half-life 18 h, ALT 36 h; the ratio’s meanings; pyridoxal phosphate in assays.
- 30Dobrijević D, Pastor K. When hemolysis misleads: implications for the clinical interpretation of enzyme activities in pediatric samples.doi:10.3390/medicina62091724 · PMID 42796331
Hemolysis raised LDH and AST most.
- 31Liang J, Chu V, Che E, et al. FGF21 elevation is a biomarker of citrin deficiency and its metabolic dysregulation in pediatric patients.doi:10.1016/j.ymgme.2026.110262 · PMID 42771915
29 children, 67 samples, and the mouse mechanism carried into patients.
- 32Hung YE, Chiu YI, Shiesh SC, et al. The influence of haemolysis in patient samples on biochemical tests analysed using Roche Cobas8000 analyzer.doi:10.1177/00045632251356827 · PMID 40551378
Hemolysis bias exceeded reference change values for AST.
- 33Riboli E, Beland FA, Lachenmeier DW, et al. Carcinogenicity of aspartame, methyleugenol, and isoeugenol.doi:10.1016/S1470-2045(23)00341-8 · PMID 37454664
The IARC Monographs summary: aspartame group 2B.
- 34Goodman JE, Boon DN, Jack MM. Perspectives on recent reviews of aspartame cancer epidemiology.doi:10.1016/j.gloepi.2023.100117 · PMID 37637718
JECFA kept the ADI; epidemiology not convincing.
- 35Zhu X, Welsh JA, McCullough ML, et al. Association between aspartame consumption and cancer risk: evidence from a large prospective cohort.doi:10.1016/j.tjnut.2026.101460 · PMID 41765137
100,004 adults, 21,356 cancers, and no dose–response in any outcome — which its own authors say first.
- 36Bonaccio M, Di Castelnuovo A, Costanzo S, et al. Urinary concentrations of non-nutritive sweeteners and breast cancer: a case-cohort analysis of the Moli-sani study.doi:10.3390/nu18182958 · PMID 42796941
The first study to measure the exposure instead of asking about it.
- 37Crick DCP, Liu W, Hwang LD. Investigating the relationship between taste perception of artificial sweeteners and cancer risk.doi:10.1017/S1368980026101827 · PMID 41521718
The first genetic-instrument attempt on the sweetener question, from a taste-perception GWAS of 1,757 adolescents.
- 38Willoughby DS, Leutholtz B. D-aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men.doi:10.1016/j.nutres.2013.07.010 · PMID 24074738
3 g/day, 28 days: no effect.
- 39Melville GW, Siegler JC, Marshall PW. Three and six grams supplementation of D-aspartic acid in resistance trained men.doi:10.1186/s12970-015-0078-7 · PMID 25844073
24 men; 6 g/day lowered total testosterone.
- 40GamalEl Din SF, Elnashar AM, Elkhiat Y, et al. Evaluation of supplementation of 2660 mg D-aspartic acid and 200 mg ubiquinol and 10 mg zinc on different semen parameters in idiopathic male infertility: a randomized double blind placebo controlled study.doi:10.4081/aiua.2025.13554 · PMID 40248985
Three ingredients in one capsule, 48 men analyzed. It cannot say which one did anything.
- 41Attinger MC, von Felten S, Rodrigues CL, Krützfeldt J, Risch L, Bonzon J. Single center, open-label, randomized crossover trial on drug-drug interactions of levothyroxine/magnesium-citrate and levothyroxine/magnesium-aspartate in healthy subjects — the ThyroMag trial.doi:10.1111/cts.70409 · PMID 41221788
The aspartate salt measurably worse than the citrate salt, against a drug with a narrow therapeutic index.
- 42Okamoto M, Okano Y, Okano M, et al. Food preferences of patients with citrin deficiency.doi:10.3390/nu13093123 · PMID 34579000
Carbohydrate the strongest predictor of aversion.
- 43Tiwari V, Jin B, Sun O, et al. Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency.doi:10.1038/s42255-025-01399-3 · PMID 41238906
Why people with citrin deficiency do not like sweets, answered as a liver-to-brain signal.
- 44Wu W, Sui W, Chen S, et al. Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation.doi:10.1016/j.cmet.2025.01.006 · PMID 39978336
Mice and monkeys, a vagotomy that abolishes the effect, and a mechanism that is not about the aspartate.
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