Изоцитрат дегидрогеназа ферменті және оның қатысуы

Class of enzymes

Isocitrate dehydrogenase (IDH) and is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha ketoglutarate (α ketoglutarate) and CO2. This is a two step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and use NADP+ as a cofactor instead of NAD+. They localize to the cytosol as well as the mitochondrion and peroxisome.

[[File:Porcine Mitochondrial IDH surface with greenpocket. jpg|thumb|right|300px|One active site on the Porcine NADP+ dependent enzyme (green). as glioblastomas. Similar to human R132H ICDH, Mtb ICDH 1 also catalyzes the formation of α hydroxyglutarate.

The IDH step of the citric acid cycle is often (but not always) an irreversible reaction due to its large negative change in free energy. It must therefore be carefully regulated to avoid depletion of isocitrate (and therefore an accumulation of alpha ketoglutarate). The reaction is stimulated by the simple mechanisms of substrate availability (isocitrate, NAD+ or NADP+, Mg2+ / Mn2+ ), product inhibition by NADH (or NADPH outside the citric acid cycle) and alpha ketoglutarate, and competitive feedback inhibition by ATP. A conserved ncRNA upstream of the icd gene which codes for NADP+ dependent isocitrate dehydrogenase (IDH) has been reported in bacterial genomes, due to its characteristics this ncRNA resembles previous regulatory motifs called riboswitches, icd II ncRNA motif has been proposed as a strong candidate riboswitch.

Within the citric acid cycle, isocitrate, produced from the isomerization of citrate, undergoes both oxidation and decarboxylation. The enzyme isocitrate dehydrogenase (IDH) holds isocitrate within its active site using the surrounding amino acids, including arginine, tyrosine, asparagine, serine, threonine, and aspartic acid. In the provided figure, the first box shows the overall isocitrate dehydrogenase reaction. The necessary reactants for this enzyme mechanism are isocitrate, NAD+/NADP+, and Mn2+ or Mg2+. The products of the reaction are alpha ketoglutarate, carbon dioxide, and NADH + H+/NADPH + H+. This reaction results in the formation of alpha ketoglutarate, NADH + H+/NADPH + H+, and CO2.