oxaloacétate

Oxaloacétate, also known as oxaloacetate (OAA), is a four-carbon dicarboxylic α-keto acid that functions as a central metabolite in carbohydrate and amino acid metabolism. It is a key intermediate of the citric acid cycle (Krebs cycle) and participates in the regeneration of the cycle by accepting acetyl-CoA to form citrate, which proceeds through the cycle to ultimately reform oxaloacetate.

Anaplerosis and the citric acid cycle: Oxaloacétate can be replenished in the mitochondria from pyruvate via pyruvate carboxylase, an ATP- and biotin-dependent enzyme. This anaplerotic input helps sustain TCA cycle flux when intermediates are siphoned off for biosynthesis, supporting continuous energy production and biosynthetic needs.

Gluconeogenesis and carbon flow: In gluconeogenesis, oxaloacétate is a pivotal branch point. In liver and kidney cortex, it is converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (PEPCK) with the concomitant release of CO2 and GTP, enabling the synthesis of glucose from non-carbohydrate precursors.

Amino acid metabolism and transport: Oxaloacétate participates in transamination reactions, notably forming aspartate through the action of aspartate aminotransferase, linking carbon and nitrogen metabolism and feeding the TCA cycle via α-ketoglutarate.

Transport and localization: Oxaloacétate does not cross membranes readily; its interconversion with malate via malate dehydrogenase enables shuttle systems (malate-oxaloacetate shuttle) that balance redox equivalents between cellular compartments. In plants and microbes, these reactions support respiration, photosynthesis, and metabolic flexibility.