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Oxaloacetic Acid

C4H4O5 organic

Properties

StateSolid (white to pale yellow crystalline powder; unstable)
ColorWhite to pale yellow
SolubilitySoluble in water; spontaneously decarboxylates to pyruvate in solution
Melting Point161 °C (decomposes)
Boiling PointDecomposes before boiling

About Oxaloacetic Acid

Oxaloacetic acid (OAA, oxaloacetate at physiological pH) is a 4-carbon dicarboxylic alpha-ketoacid with the formula C4H4O5 and a molar mass of 132.071 g/mol. It sits at the busiest intersection in central metabolism. Citrate synthase grabs OAA, condenses it with acetyl-CoA, and starts the citric acid cycle — and after one full turn, OAA is regenerated. That regeneration is what makes the TCA cycle catalytic with respect to oxaloacetate: a single OAA molecule can shuttle through the cycle thousands of times, oxidizing acetyl-CoA after acetyl-CoA. OAA is also the substrate that PEP carboxykinase (PEPCK) phosphorylates and decarboxylates to make phosphoenolpyruvate, the committed step of gluconeogenesis. It is the keto partner of aspartate (one transamination away), the input to the malate-aspartate shuttle that moves cytosolic NADH into mitochondria, and the anaplerotic refill point that pyruvate carboxylase produces from pyruvate and CO2 when cycle intermediates run low. Chemically, free OAA is unstable — the beta-keto acid spontaneously decarboxylates to pyruvate plus CO2 on the bench, with a half-life of hours at room temperature in aqueous solution. Cells get away with it because steady-state OAA in mitochondria is held below 10 micromolar.

Where you'll encounter it

If you've ever measured aspartate aminotransferase (AST) on a clinical chemistry panel, you measured OAA chemistry — the assay couples the AST-catalyzed transfer of the alpha-amino group from aspartate to alpha-ketoglutarate (which produces oxaloacetate) to malate dehydrogenase running in reverse, consuming NADH whose absorbance drop at 340 nm gives the rate. Cardiac troponin replaced AST as the preferred MI marker, but the chemistry is still in every clinical analyzer for liver function panels. In a research biochem lab, you store OAA stock solutions on ice and use them within an hour because they decarboxylate as you watch. Metabolic flux analysis with 13C-labeled OAA tracers has become the standard way to map cancer-cell rewiring of the TCA cycle, particularly the reductive carboxylation pathway that hypoxic tumors use to make citrate from glutamine.

Common Uses

  • Substrate for citrate synthase in the citric acid cycle (TCA condensation step)
  • Gateway substrate for gluconeogenesis through PEP carboxykinase (PEPCK)
  • Anaplerotic product of pyruvate carboxylase, refilling depleted TCA intermediates
  • Coupled-enzyme assay component for clinical AST measurement and lactate dehydrogenase studies
  • Tracer substrate in 13C metabolic flux analysis of cancer and hypoxia metabolism

Safety Information

Non-toxic at the concentrations seen in cells. Bench-grade OAA can cause mild skin and eye irritation from its acidity. GHS: H315 (skin irritation), H319 (eye irritation). The bigger handling issue is chemical instability — solid OAA must be stored desiccated at -20 °C and solutions must be made fresh in cold buffer and used within an hour. Decomposition products (pyruvate and CO2) are themselves harmless but make stock concentrations unreliable for kinetics work if you let the bottle warm up.

This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.

Constituent Elements

Frequently Asked Questions

What is the molar mass of oxaloacetic acid?
The molar mass of oxaloacetic acid (C4H4O5) is 132.071 g/mol, calculated from 4 carbon (4 x 12.011 = 48.044) + 4 hydrogen (4 x 1.008 = 4.032) + 5 oxygen (5 x 15.999 = 79.995). For enzyme assays, weigh out the disodium salt (Na2C4H2O5, 176.04 g/mol) instead — it dissolves faster, is less acidic, and is what most coupled-assay protocols specify.
Why is oxaloacetate so important in metabolism?
OAA is the metabolic switchboard. It condenses with acetyl-CoA to start the TCA cycle, gets converted to PEP by PEPCK to start gluconeogenesis, exchanges its alpha-keto group with aspartate via AST in amino acid metabolism, and feeds the malate-aspartate shuttle that imports cytosolic NADH into mitochondria. When TCA intermediates leak away into biosynthesis (heme, glutamate, aspartate), pyruvate carboxylase regenerates OAA from pyruvate and CO2 — the anaplerotic step that keeps the cycle from grinding to a halt.
What happens when oxaloacetate levels are low?
The TCA cycle slows because there's no OAA to receive the next acetyl-CoA, and acetyl-CoA backs up. In starvation or untreated diabetes, cells are oxidizing fatty acids hard, generating acetyl-CoA that has nowhere to go because OAA has been drained off into gluconeogenesis. The excess acetyl-CoA gets diverted into ketone body synthesis (acetoacetate, beta-hydroxybutyrate, acetone) — this is the biochemical basis of ketosis and, in extreme cases, diabetic ketoacidosis. The old saying 'fats burn in the flame of carbohydrates' captures exactly this OAA dependency.