isocitrate + NADP+ => alpha-ketoglutarate + CO2 + NADPH + H+ [IDH2]

Stable Identifier
R-HSA-450984
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

Mitochondrial isocitrate dehydrogenase IDH2 catalyzes the irreversible reaction of isocitrate and NADP+ to form alpha ketoglutarate, CO2, and NADPH + H+ (Hartong et al. 2008). The structure of the active human enzyme has not been determined experimentally, but is inferred to be a homodimer with one Mn++ bound to each subunit based on detailed studies of the homologous pig enzyme (Ceccarelli et al. 2002). NADP-specific IDH2 was the first isocitrate dehydrogenase isoenzyme to be characterized in biochemical studies of the mammalian TCA cycle (Ochoa 1948). Later work with yeast revealed the existence of both NADP-specific (IDH2-homologous) and NAD-specific (IDH3-homologous) enzymes and demonstrated the ADP-dependence of the latter (Kornberg and Pricer 1951), consistent with the now widely accepted view that IDH3 mediates the conversion of isocitrate to alpha-ketoglutarate in the TCA cycle. The physiological function of IDH2 is thus unclear. The recent observation that individuals homozygous for IDH3 mutations that sharply reduce its activity do not show symptoms of deficient energy metabolism in most tissues raises the possibility that the IDH2 reaction may play an accessory role in the TCA cycle (Hartong et al. 2008).

Literature References
PubMed ID Title Journal Year
12207025 Crystal structure of porcine mitochondrial NADP+-dependent isocitrate dehydrogenase complexed with Mn2+ and isocitrate. Insights into the enzyme mechanism

Ceccarelli, C, Grodsky, NB, Ariyaratne, N, Colman, RF, Bahnson, BJ

J Biol Chem 2002
14832224 Di- and triphosphopyridine nucleotide isocitric dehydrogenases in yeast

Kornberg, A, Pricer, WE Jr

J Biol Chem 1951
18914071 Biosynthesis of tricarboxylic acids by carbon dioxide fixation; enzymatic mechanisms

Ochoa, S

J Biol Chem 1948
18806796 Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle

Hartong, DT, Dange, M, McGee, TL, Berson, EL, Dryja, TP, Colman, RF

Nat Genet 2008
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
isocitrate dehydrogenase (NADP+) activity of IDH2 dimer [mitochondrial matrix]
Physical Entity
Activity
Orthologous Events
Authored