Isocitrate dehydrogenase reaction catalyzed

Avidin blocks the reaction, an observation which suggests that biotin is required for the decarboxylation. The malic enzyme catalyzes the decarboxylation of malic acid to pyruvic acid. The reverse of the reaction leads to the formation of the dicarboxylic acid at the expense of a pyruvic acid. The malic enzyme has many properties in common with isocitric dehydrogenase. It catalyzes an oxidative decarboxylation. Its coenzyme, NADP, acts as a hydrogen acceptor, and no intermediate has been isolated in the reaction. The molecular mechanism of the reaction is not known. 

Step 3 of Figure 29.12 Oxidation and Decarboxylation (2K,3S)-lsocitrate, a secondary alcohol, is oxidized by NAD+ in step 3 to give the ketone oxalosuccinate, which loses C02 to givea-ketoglutarate. Catalyzed by isocitrate dehydrogenase, the decarboxylation is a typical reaction of a /3-keto acid, just like that in the acetoacetic ester synthesis (Section 22.7). The enzyme requires a divalent cation as cofactor, presumably to polarize the ketone carbonyl group. 

Some of the results obtained by differential centrifugation showed enzyme distribution between different cell fractions which were difficult to interpret. Enzymes like carbamoyl phosphate synthase or isocitrate dehydrogenase were found both in mitochondria and in the soluble fraction of the cell. This led to detailed kinetic studies with purified enzymes which indicated there might be populations of enzymes with slightly different properties (isozymes) catalyzing similar reactions in different compartments or in different cell types. Variations in kinetic behavior appeared to tailor the enzyme appropriately to the particular compartment or cell where the reaction took place. 

The first step is carboxylation of acetyl CoA to malonyl CoA. This reaction is catalyzed by acetyl-CoA carboxylase [5], which is the key enzyme in fatty acid biosynthesis. Synthesis into fatty acids is carried out by fatty acid synthase [6]. This multifunctional enzyme (see p. 168) starts with one molecule of ace-tyl-CoA and elongates it by adding malonyl groups in seven reaction cycles until palmi-tate is reached. One CO2 molecule is released in each reaction cycle. The fatty acid therefore grows by two carbon units each time. NADPH+H is used as the reducing agent and is derived either from the pentose phosphate pathway (see p. 152) or from isocitrate dehydrogenase and malic enzyme reactions. 

The reactions catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase are both oxidative decarboxylation reactions. How similar are the reactions ... 

In animals the acetyl CoA produced from fatty acid degradation cannot be converted into pyruvate or oxaloacetate. Although the two carbon atoms from acetyl CoA enter the citric acid cycle, they are both oxidized to C02 in the reactions catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase (see... 

Oxidation of isocitrate to a-ketoglutarate (catalyzed by isocitrate dehydrogenase the reaction requires NAD+). 

The first enzyme of the citric acid cycle to catalyze both the release of one carbon dioxide and the reduction of NAD+ is isocitrate dehydrogenase. The overall reaction of this step is as follows ... 

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. 

Isocitrate dehydrogenase (E.C. 1.1.1.42, IDH) from Escherichia coli and isopropylmalate dehydrogenase (E.C. 1.1.1.85, IMDH) from Thermus thermophilus are involved in Krebs cycle and leucine biosynthesis respectively. Both enzymes catalyze the sequential reactions... 

Much has been published on the controversial subject of the control of glycolysis. The following brief summary of some of the controls responsible for the Pasteur effect in yeasts is based mainly on a review by Sols and coworkers144 (see also, Fig. 7). (i) Isocitrate dehydrogenase (NAD ) (EC 1.1.1.41), one of the controlling enzymes of the tricarboxylic acid cycle (see Fig. 5), catalyzes the reaction... 

Enzyme activators are substances, often inorganic ions, that are required for certain enzymes to become active as catalysts. Activators can be determined by their effect on the rates of enzyme-catalyzed reactions. For example, it has been reported that magnesium at concentrations as low as 10 ppb can be determined in blood plasma based on activation by this ion of the enzyme isocitric dehydrogenase. 

Isocitrate dehydrogenase catalyzes the first of two decarboxylations and dehydrogenations in the cycle. Three different isocitrate dehydrogenases are present one specific for NAD+ and found only in mitochondria, the other two specific for NADP+ and found in mitochondria and cytoplasm. The NAD -specific enzyme is the primary enzyme with regard to TCA cycle operation. All three require Mg + or Mn +. The reaction yields a-ketoglutarate (2-oxoglutarate), NAD(P)H, and CO2 and involves enzyme-bound oxalosuccinate as an intermediate. 

Keto-6-phosphogluconate is a probable intermediate. The reaction is similar to those catalyzed by malic enzyme (in gluconeogenesis) and by isocitrate dehydrogenase (in the TCA cycle). 

It is important to note that animals are unable to effect the net synthesis o/glu-cose from fatty acids. Specifically, acetyl Go A cannot be converted into pyruvate or oxaloacetate in animals. Recall that the reaction that generates acetyl CoA from pyruvate is irreversible (p. 477). The two carbon atoms of the acetyl group of acetyl CoA enter the citric acid cycle, but two carbon atoms leave the cycle in the decarboxylations catalyzed by isocitrate dehydrogenase and a-ke-toglutarate dehydrogenase. Consequently, oxaloacetate is regenerated, hut it is not formed de novo when the acetyl unit of acetyl CoA is oxidized by the citric acid cycle. In contrast, plants have two additional enzymes enabling them to convert the carbon atoms of acetyl CoA into oxaloacetate (Section 18.4.). 

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