Reaction: isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+ (overall reaction)
(1a) isocitrate + NADP+ = oxalosuccinate + NADPH + H+
(1b) oxalosuccinate = 2-oxoglutarate + CO2
For diagram click here or here.
Glossary: isocitrate = (1R,2S)-1-hydroxypropane-1,2,3-tricarboxylate (previously known as threo-DS-isocitrate)
oxalosuccinate = 1-oxopropane-1,2,3-tricarboxylate
Other name(s): oxalosuccinate decarboxylase; isocitrate dehydrogenase (NADP); oxalsuccinic decarboxylase; isocitrate (NADP) dehydrogenase; isocitrate (nicotinamide adenine dinucleotide phosphate) dehydrogenase; NADP-specific isocitrate dehydrogenase; NADP-linked isocitrate dehydrogenase; NADP-dependent isocitrate dehydrogenase; NADP isocitric dehydrogenase; isocitrate dehydrogenase (NADP-dependent); NADP-dependent isocitric dehydrogenase; triphosphopyridine nucleotide-linked isocitrate dehydrogenase-oxalosuccinate carboxylase; NADP+-linked isocitrate dehydrogenase; IDH (ambiguous); dual-cofactor-specific isocitrate dehydrogenase; NADP+-ICDH; NADP+-IDH; IDP; IDP1; IDP2; IDP3
Systematic name: isocitrate:NADP+ oxidoreductase (decarboxylating)
Comments: Requires Mn2+ or Mg2+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+), oxalosuccinate can be used as a substrate. In eukaryotes, isocitrate dehydrogenase exists in two forms: an NAD+-linked enzyme found only in mitochondria and displaying allosteric properties, and a non-allosteric, NADP+-linked enzyme that is found in both mitochondria and cytoplasm [6]. The enzyme from some species can also use NAD+ but much more slowly [6,7].
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9028-48-2
References:
1. Agosin, M.U. and Weinbach, E.C. Partial purification and characterization of the isocitric dehydrogenase from Trypanosoma cruzi. Biochim. Biophys. Acta 21 (1956) 117-126. [PMID: 13363868]
2. Moyle, J. and Dixon, M. Purification of the isocitrate enzyme (triphosphopyridine nucleotide-linked isocitrate dehydrogenase-oxalosuccinate carboxylase). Biochem. J. 63 (1956) 548-552. [PMID: 13355848]
3. Plaut, G.W.E. Isocitrate dehydrogenases. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds.), The Enzymes, 2nd ed., vol. 7, Academic Press, New York, 1963, p. 105-126.
4. Siebert, G., Dubuc, J., Warner, R.C. and Plaut, G.W.E. The preparation of isocitrate dehydrogenase from mammalian heart. J. Biol. Chem. 226 (1957) 965-975. [PMID: 13438885]
5. Vickery, H.B. A suggested new nomenclature for the isomers of isocitric acid. J. Biol. Chem. 237 (1962) 1739-1741. [PMID: 13925783]
6. Camacho, M.L., Brown, R.A., Bonete, M.J., Danson, M.J. and Hough, D.W. Isocitrate dehydrogenases from Haloferax volcanii and Sulfolobus solfataricus: enzyme purification, characterisation and N-terminal sequence. FEMS Microbiol. Lett. 134 (1995) 85-90. [PMID: 8593959]
7. Steen, I.H., Lien, T. and Birkeland, N.-K. Biochemical and phylogenetic characterization of isocitrate dehydrogenase from a hyperthermophilic archaeon, Archaeoglobus fulgidus. Arch. Microbiol. 168 (1997) 412-420. [PMID: 9325430]
8. Koh, H.J., Lee, S.M., Son, B.G., Lee, S.H., Ryoo, Z.Y., Chang, K.T., Park, J.W., Park, D.C., Song, B.J., Veech, R.L., Song, H. and Huh, T.L. Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism. J. Biol. Chem. 279 (2004) 39968-39974. [PMID: 15254034]
9. Ceccarelli, C., Grodsky, N.B., Ariyaratne, N., Colman, R.F. and Bahnson, B.J. Crystal structure of porcine mitochondrial NADP+-dependent isocitrate dehydrogenase complexed with Mn2+ and isocitrate. Insights into the enzyme mechanism. J. Biol. Chem. 277 (2002) 43454-43462. [PMID: 12207025]