Decarboxylation of isocitrate

The oxidative decarboxylation of isocitrate to a-kctoglutaratc, catalyzed by mitochondrial isocitrate dehydrogenase. The intermediate, oxalosuccinate, is not released from the enzyme. B represents a catalytic side chain from the enzyme. 

We come now to the first of four oxidation-reduction reactions in the citric acid cycle. The oxidative decarboxylation of isocitrate is catalyzed by isocitrate dehydrogenase. 

Four pairs of hydrogen atoms leave the cycle in four oxidation reactions. Two molecules of NAD+ are reduced in the oxidative decarboxylations of isocitrate and a -ketoglutarate, one molecule of FAD is reduced in the oxidation of succinate, and one molecule of NAD+ is reduced in the oxidation of malate. 

Oxidative decarboxylation of isocitrate to a-ketoglutarate. A P-ketoacid intermediate is formed in both reactions. See question... 

Aconitase catalyzes the isomerization of citrate to isodtrate, isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate, and a-ketoglutarate dehydrogenase catalyzes the oxidative decarboxylation of a-keto-glutarate to succinyl-CoA. Succinyl-CoA and the remaining intermediates are the 4-carbon intermediates of the Krebs cycle. Succinyl thiokinase catalyzes the release of coenzyme A from succinyl-CoA and the production of GTP. Succinate dehydro-... 

Isocitrate is oxidized to form NADH and C02. The oxidative decarboxylation of isocitrate, catalyzed by isocitrate dehydrogenase, occurs in two steps. First, isocitrate is oxidized to form oxalosuccinate, a transient intermediate ... 

Oxidation and decarboxylation of isocitrate to a-ketoglutarate. Isocitrate dehydrogenase is also an allosteric enzyme however, the enz)une is controlled by the positive allosteric effector, ADP. ADP is a signal that the levels of ATP must be low, and therefore the rate of the citric acid cycle should be increased. Interestingly, isocitrate dehydrogenase is also inhibited by high levels of NADH and ATP. 

Fig. 20.5. Oxidation and decarboxylation of isocitrate. The alcohol group (C—OH) is oxidized to a ketone, with the C—H electrons donated to NAD as the hydride ion. Subsequent electron shifts in the pyridine ring remove the positive charge. The H of the OH group dissociates into water as a proton, H. NAD, the electron acceptor, is reduced.

Note that in the oxidative decarboxylation of 6-phosphogluconate, oxidation occurs at the carbon [3 to the carboxyl group. A similar [3-oxidation occurs during the decarboxylation of isocitrate in the citric acid cycle. In both cases a (3-keto acid intermediate is formed. Since (3-keto acids are relatively unstable, they are easily decarboxylated. 

The chief source of glutamic add is a-ketoglutaric add produced in the Krebs cycle. This add can itself only arise in the oxidative decarboxylation of isocitric acid, for the decarboxylation of a-ketoglutarate to give succinate is irreversible. This is the sole pathway for the formation of glutamic add from carbohydrate. 

A widely distributed cytoplasmic enzyme which catalyses the oxidative decarboxylation of isocitrate to n-oxoglutarate, a reaction which is accompanied by the reduction of NADP tc NADPH. (A mitochondrial enzyme also exists which uses NAC as a cofactor.) Elevated serum levels are found in liver disease. Ii can be measured by following the reduction of NADP bj ultraviolet spectrophotometry. 

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