Isocitrato

Isocitrato, known in English as isocitrate, is the tricarboxylate anion of isocitric acid and an isomer of citrate. It is an essential intermediate in the citric acid cycle (Krebs cycle), a central pathway of cellular respiration that takes place in the mitochondria of aerobic organisms.

In the cycle, citrate is converted to isocitrate by the enzyme aconitase, via a cis-aconitate intermediate. Isocitrate is then oxidatively decarboxylated by isocitrate dehydrogenase to alpha-ketoglutarate, releasing carbon dioxide and producing reducing equivalents in the form of NADH (in most organisms; some systems generate NADPH instead, depending on the enzyme isoform). This oxidative step supplies a significant portion of the cell’s NADH for ATP production through oxidative phosphorylation and contributes to anabolic processes via its connection to alpha-ketoglutarate, a key metabolite in amino acid biosynthesis.

Regulation of isocitrate flux depends on cellular energy status. In mitochondria, isocitrate dehydrogenase activity is inhibited by high NADH and activated by ADP or Ca2+ in certain tissues, linking the TCA cycle to energy demand. In plants and many bacteria, the glyoxylate cycle can repurpose isocitrate by cleavage into succinate and glyoxylate, enabling growth on C2 compounds like acetate.

Medical relevance includes alterations in isocitrate dehydrogenase (IDH) activity. Mutations in IDH1 or IDH2 can produce the oncometabolite 2-hydroxyglutarate, contributing to the pathogenesis of certain cancers. Isocitrato appears in biochemical texts and databases as the Spanish name for isocitrate.