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Isocitrate dehydrogenase is an enzyme that is used in the Krebs cycle to
catalyze the oxidative decarboxylation of isocitrate. (5) The enzyme is
classified as an oxidoreductase. The Krebs cycle, also known as the tricarboxylic
acid (TCA) cycle, is part of the citric acid cycle (4). The citric acid
cycle is used to oxidate fuel molecules and takes place inside mitochondria.
Fuels enter the cycle as acetyl CoA. The complete oxidation of acetyl CoA
yields one molecule of guanosine triphosphate (GTP) and four pairs of electrons
in the form of three NADH molecules and one FADH2
molecule. Electrons are transferred to oxygen through the electron transport
chain (ETC); the ETC creates a proton gradient that drives the synthesis
of ATP. An animal cell’s needs for ATP are met by varying the rate of the
citric acid cycle (1)
One primary control point in the TCA cycle is the allosteric enzyme isocitrate dehydrogenase (1). Isocitrate dehydrogenase catalyzes the third step of the citric acid cycle (6). The conversion of isocitrate to a-ketoglutarate is a two-step process: the oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), then the decarboxylation of the carboxyl group beta to the ketone, producing ?-ketoglutarate. Another isoform of the enzyme catalyzes the same reaction, but it is unrelated to the citric acid cycle, occurs in the cytosol and the mitochondrion, and uses nicotinamide adenine dinucleotide phosphate (NADP+) instead of NAD+ (6).
In mammals, there are three classes of isocitrate dehydrogenase isoenzymes:
mitochondrial NAD+–dependent isocitrate dehydrogenase (IDH), mitochondrial
NADP+–dependent isocitrate dehydrogenase (IDPm), and cytosolic NADP+–dependent
isocitrate dehydrogenase (IDPc) (7). Each is responsible for a different
function of isocitrate dehydrogenase.
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