Isocitrate dehydrogenase

Isocitrate dehydrogenase ( IDH ) is the name for enzymes and enzyme complexes that catalyze the oxidative cleavage of carbon dioxide of isocitrate, wherein α -ketoglutarate is formed. This reaction is part of the citric acid cycle and therefore central in the metabolism of all living beings. The reverse reaction, which occurs only in some bacteria use the enzyme isocitrate lyase.

The catalyzed reaction:

From CO2 isocitrate is cleaved and ketoglutarate to form.

Structurally, IDH of alternating α - layers and β - sheets in a sandwich arrangement. There are two different groups of enzymes, depending on whether NAD ( EC 1.1.1.41 ) or NADP ( EC 1.1.1.42 ) is a cofactor. Both Mg2 or Mn2 as the metal ion. Homologs of the first group consists of three subunits ( heterotetramer ααβγ ) and are located in the mitochondrion, while the second group are homodimers, each isoform in the mitochondrion and in the cytosol. IDH occur in all living things. In humans, the three IDH isoforms are encoded in five genes whose defects can lead to inherited metabolic disorders:

The first step in the successful oxidation of isocitrate 1 provides next to NADH 2- oxo carboxylic acid Oxalsuccinat 2, which complexed as a bidentate ligand via the keto group and the carboxyl group to alpha position the metal ion (Mn 2 or Mg 2 ). Characterized due to the carbonyl is polarized, the inclination of which the beta-position carboxy group to decarboxylation greatly increased, so that the forming of the complex formation stabilized enol form of the 2- 3 in the subsequent decarboxylation Oxoglutarats. After protonation of the 2- oxoglutarate 4 is released. Mitochondrial NAD -dependent isocitrate dehydrogenase, unlike the NADP -dependent binding no Oxalsuccinat as substrate to form 2-oxoglutarate.

Like any dehydrogenase is also the isocitrate dehydrogenase regulated by ATP or ADP. ATP causes an indirect inhibition, ADP, as they interact with an indirect activation of the dehydrogenase of the kinase subunit. ATP stimulates the kinase subunit, this phosphorylates the subunit I of the isocitrate dehydrogenase, which results in their inactivation by itself. ADP and accordingly acts as an antagonist results in an indirect activation of the isocitrate dehydrogenase. This regulatory process by phosphorylation and dephosphorylation is called interconversion.