Oxaloacetate

Oxaloacetate, also known as oxaloacetic acid, is a four‑carbon dicarboxylic acid that contains a keto group. In its neutral form the common structural representation is HOOC‑CO‑CH2‑COOH, and at physiological pH it mainly exists as the dianion due to deprotonated carboxyl groups. Its chemical formula is C4H4O5.

In metabolism, oxaloacetate is a central intermediate of the citric acid cycle (Krebs cycle). It condenses with acetyl‑CoA to form citrate, catalyzed by citrate synthase, thereby initiating the cycle. Oxaloacetate is regenerated near the end of the cycle from malate by malate dehydrogenase, enabling continuous turnover of the cycle. It also participates in transamination reactions, most notably serving as the amino group acceptor to form aspartate via aspartate aminotransferase.

Oxaloacetate is also a key hub in glucose biosynthesis. In gluconeogenesis, pyruvate carboxylase can carboxylate pyruvate to oxaloacetate in mitochondria, providing a substrate for glucose production. Oxaloacetate can then be converted to phosphoenolpyruvate by PEP carboxykinase, contributing to the generation of glucose and related sugars. Through these connections, oxaloacetate links energy production, amino acid metabolism, and carbohydrate production.

Location and transport are related to its metabolic roles. Oxaloacetate is produced in mitochondria and, via shuttle systems such as the malate–aspartate shuttle, can be transported to the cytosol when needed for gluconeogenesis or biosynthetic processes. Its availability influences the flux through multiple metabolic pathways and overall cellular energy balance.