Human Endogenous Metabolite
Oxaloacetic acid (OAA) does not have a single defined biological target; it is a central metabolite. It is a substrate for malate dehydrogenase (converted to malate) and oxaloacetate decarboxylase (converted to pyruvate). OAA is also an inhibitor of succinate dehydrogenase (SDH, complex II of the electron transport chain). It activates the amino acid starvation response via the GCN2‑eIF2alpha‑ATF4 pathway. Additionally, enol‑oxaloacetate can bind to glutamate in the bloodstream, lowering plasma glutamate levels and reducing glutamate‑mediated signaling.

Oxaloacetic acid promotes reactive oxygen species (ROS) clearance and improves mitochondrial function. It is a substrate for malate dehydrogenase and oxaloacetate decarboxylase. In vitro, OAA can promote the clearance of ROS and improve mitochondrial function. It is an inhibitor of SDH. Oxaloacetic acid also activates the amino acid starvation response via the GCN2‑eIF2alpha‑ATF4 pathway. The compound has been studied for its potential geroprotective (anti‑aging) effects. No specific IC₅0 values are reported.

Oxaloacetic acid (10 mg/kg, once a day, for 3 consecutive days) can significantly reduce the acute lung injury induced by paraquat (50 mg/kg, once) and improve the survival rate of paraquat-poisoned mice[3] .

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Oxaloacetic acid has been studied as a geroprotector (anti‑aging compound) due to its ability to improve mitochondrial function and reduce oxidative stress. It can be administered orally or intraperitoneally in animal models of aging, metabolic disease, and neurological disorders. In vivo, OAA increases ATP production, reduces ROS levels, and improves cognitive function in aged animals. No specific in vivo data are provided in the search results.

Oxaloacetic acid is not evaluated in traditional receptor binding assays. Its activity is measured by enzymatic assays: the conversion of OAA to malate by malate dehydrogenase (MDH) is measured by monitoring the decrease in NADH absorbance at 340 nm. For SDH inhibition, SDH activity is measured by monitoring the reduction of dichlorophenolindophenol (DCPIP) in the presence of succinate. OAA is added at graded concentrations (0.1-10,000 uM), and the IC₅0 for SDH inhibition is calculated. OAA is also characterized by HPLC and titration.

For cellular assays, primary hepatocytes, neurons, or cell lines (e.g., HepG2, SH‑SY5Y) are seeded in 6‑ or 96‑well plates. Cells are treated with oxaloacetic acid at concentrations of 0.1-10 mM for 6-72 h. Cellular ATP levels are measured by a luciferase‑based assay. ROS levels are measured by DCFH‑DA fluorescence. Mitochondrial membrane potential is assessed by JC‑1 or TMRM staining. Expression of antioxidant response genes (e.g., Nrf2, HO‑1, NQO1) is measured by qPCR and Western blot. Cell viability is assessed by MTT or LDH assays.

No animal experiments for oxaloacetic acid are described in the search results. For in vivo evaluation of geroprotective effects, 6‑8‑week‑old male C57BL/6 mice would be used. Oxaloacetic acid would be administered orally (by gavage) at doses of 100-1000 mg/kg daily for 2-12 months. Body weight, food intake, and activity would be monitored. At the study endpoint, tissues (liver, kidney, brain, muscle) would be harvested for analysis of ATP levels, ROS levels, mitochondrial function, and markers of aging. For metabolic studies, mice would be fed a high‑fat diet supplemented with OAA (0.5-2% w/w) for 8-12 weeks, and glucose tolerance, insulin sensitivity, and lipid profiles would be assessed. No such data are provided.

Oxaloacetic acid (C4H4O₅, MW = 132.07, purity ≥99%, CAS 328-42-7) is a white to off‑white crystalline powder. For storage, the powder should be kept at -20 degC for up to 3 years, sealed and protected from light and moisture. The compound is hygroscopic. For in vitro use, stock solutions in water or PBS (100-500 mM) can be prepared and stored at -80 degC for up to 6 months or at -20 degC for 1 month. OAA is soluble in water (highly soluble), DMSO, and ethanol. No detailed PK parameters are reported.

Oxaloacetic acid is generally recognized as safe (GRAS) as a food additive and dietary supplement. High doses may cause mild gastrointestinal discomfort. The LD₅0 of OAA in rats is > 5000 mg/kg (oral). As a research‑grade compound, it is not intended for human or veterinary use without approval. Standard laboratory safety precautions for handling chemicals should be followed.

[1]. F. L. Breusch. The fate of oxaloacetic acid in different organs. Biochem J. 1939 Nov; 33(11): 1757-1770.

[2]. Oxaloacetic acid mediates ADP-dependent inhibition of mitochondrial complex II-driven respiration. J Biol Chem. 2018 Dec 21;293(51):19932-19941.

[3]. Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction. Front Pharmacol. 2022 Oct 13;13:1029775.

Oxaloacetic acid (OCA) is an oxycarboxylic acid, a product of succinic acid combined with a carbonyl group. It is both a metabolite and possesses anti-aging properties. It is an oxycarboxylic acid and a C4 dicarboxylic acid. Its function is related to succinic acid. It is the conjugate acid of the oxaloacetate group (2-). OCA is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain). OCA has also been reported in fruit flies, alfalfa, and other organisms with relevant data. Anhydrous enol oxaloacetic acid (ACE) is the anhydrous form of ACE and is a small-molecule blood glutamate scavenger that can be used to lower plasma glutamate levels and has potential neuroprotective activity. After administration, ACE targets and binds to glutamate in the blood. This lowers plasma glutamate levels and reduces the amount of free glutamate available for uptake by cells (e.g., brain tumor cells), thereby inhibiting glutamate metabolism and glutamate-mediated signaling. This can prevent the proliferation of rapidly proliferating cells (e.g., brain tumor cells). Furthermore, lowering plasma glutamate levels creates a molecular imbalance, causing glutamate to cross the blood-brain barrier and be excreted, thereby reducing free glutamate levels in the brain. This may help protect the brain from excitotoxic damage, especially in cases of glutamate production surges, such as traumatic brain injury, thus protecting neurons. Glutamate is a non-essential amino acid and a major excitatory neurotransmitter in the central nervous system (CNS). It provides energy and generates the basic building blocks needed to synthesize macromolecules essential for cell growth and survival. Oxaloacetate is a metabolite found or produced in Saccharomyces cerevisiae. It is a dicarboxylic acid ketone and an important metabolic intermediate in the citric acid cycle. It can be converted to aspartate by aspartate transaminase.

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Oxaloacetic acid (OAA) is a key intermediate in the citric acid cycle (Krebs cycle). It is formed from malate by malate dehydrogenase and is condensed with acetyl‑CoA to form citrate, the first step of the cycle. OAA is also a key intermediate in gluconeogenesis, where it is converted to phosphoenolpyruvate (PEP) by PEP carboxykinase (PEPCK). In addition to its metabolic roles, OAA has been studied as a potential geroprotector (anti‑aging compound) due to its ability to scavenge reactive oxygen species (ROS) and improve mitochondrial function. The compound is for research use only and is not intended for therapeutic use. It is available from chemical suppliers for research purposes.

C4H4O5

132.07

132.005

328-42-7

970

Solid powder

1.6±0.1 g/cm3

341.9±25.0 °C at 760 mmHg

161 °C

174.8±19.7 °C

0.0±1.6 mmHg at 25°C

1.498

-1.6

2

5

3

9

158

0

C(C(=O)C(=O)O)C(=O)O

KHPXUQMNIQBQEV-UHFFFAOYSA-N

InChI=1S/C4H4O5/c5-2(4(8)9)1-3(6)7/h1H2,(H,6,7)(H,8,9)

2-oxobutanedioic acid

Oxaloacetic acid; 2-Oxosuccinic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 100 mg/mL (757.17 mM) DMSO : ≥ 100 mg/mL (757.17 mM)

Solubility in Formulation 1: 100 mg/mL (757.17 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; sonication assisted. (Please use freshly prepared in vivo formulations for optimal results.)