Isocitrate dehydrogenase oxidation

The first oxidative step now follows. Isocitrate dehydrogenase oxidizes the hydroxyl group of isocitrate into an 0x0 group. At the same time, a carboxyl group is released as CO2, and 2-oxoglutarate (also known as a-ketoglutarate) and NADH+H"" are formed. 

Isocitric dehydrogenase —oxidation of isocitrate to a-ketoglutarate, decarboxylation of oxalosuccinate to a-ketoglutarate. 

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. 

Figure 4. The citrate cycle. There is complete oxidation of one molecule of acetyl-CoA for each turn of the cycle CH3COSC0A + 2O2 - 2CO2 + H2O + CoASH. The rate of the citrate cycle is determined by many factors including the ADP/ATP ratio, NAD7NADH ratio, and substrate concentrations. During muscle contraction, Ca is released from cellular stores (mainly the sarcoplasmic reticulum) and then taken up in part by the mitochondria (see Table 2). Ca " activates 2-oxoglutarate and isocitrate dehydrogenases (Brown, 1992). Succinate dehydrogenase may be effectively irreversible. Enzymes ...

Isocitrate dehydrogenase Respiratory chain oxidation of 2 NADH 6... 

Figure 22-4. Sequence of reactions in the oxidation of unsaturated fatty acids, eg, linoleic acid. A -c/s-fatty acids or fatty acids forming A -c/s-enoyl-CoA enter the pathway at the position shown. NADPH for the dienoyl-CoA reductase step is supplied by intramitochondrial sources such as glutamate dehydrogenase, isocitrate dehydrogenase,and NAD(P)H transhydrogenase.

The situation is simpler for odd numbered fatty acyl derivatives as [3-oxidation proceeds normally until a 5-carbon unit remains, rather than the usual 4-carbon unit. The C5 moiety is cleaved to yield acetyl-CoA (C2) and propionyl-CoA (C3). Propionyl CoA can be converted to succinyl CoA and enter the TCA cycle so the entire molecule is utilized but with a slight reduction in ATP yield as the opportunity to generate two molecules of NADH by isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase is lost because succinyl-CoA occurs after these steps in the Krebs cycle (Figure 7.18). 

In the presence of adequate O, the rate of oxidative phosphorylation is dependent on the availability of ADR. The concentrations of ADR and ATR are reciprocally related an accumulation of ADR is accompanied by a decrease in ATR and the amount of energy available to the celL Therefore, ADR accumulation signals the need for ATR synthesis. ADR aUosterically activates isocitrate dehydrogenase, thereby increasing the rate of the citric acid cycle and the production of NADH and FADH. The elevated levels of these reduced coenzymes, in turn, increase the rate of electron transport and ATR synthesis. 

The enzyme isocitrate dehydrogenase is one of the enzymes of the Krebs or citric acid cycle, a major feature in carbohydrate metabolism (see Section 15.3). This enzyme has two functions, the major one being the dehydrogenation (oxidation) of the secondary alcohol group in isocitric acid to a ketone, forming oxalosuccinic acid. This requires the cofactor NAD+ (see Section 11.2). For convenience, we are showing non-ionized acids here, e.g. isocitric acid, rather than anions, e.g. isocitrate. 

In isocitrate, there is a CHOH group that is available for oxidation via the coenzyme NAD+ and the enzyme isocitrate dehydrogenase. NADH will then be reoxidized via oxidative phosphorylation, and lead to ATP synthesis. The oxidation product from isocitrate is oxalosuccinate, a -ketoacid that easily... 

Oudot, C. Jaquinod, M. Gortay, J.C. Cozzone, A.J. Jault, J.M. The isocitrate dehydrogenase kinase/phosphatase from Escherichia coli is highly sensitive to in-vitro oxidative conditions role of cysteine67 and cysteinel08 in the formation of a disulfide-bonded homodimer. Eur. J. Biochem., 262, 224-229 (1999)... 

MECHANISM FIGURE 16-11 Isocitrate dehydrogenase. In this reaction, the substrate, isocitrate, loses one carbon by oxidative decarboxylation. In step (T), isocitrate binds to the enzyme and is oxidized by hydride transfer to NAD+ or NADP+, depending on the isocitrate dehydrogenase isozyme. (See Fig. 14-12 for more information on hydride transfer reactions involving NAD+ and NADP+.) The resulting... 

Isocitrate dehydrogenase catalyzes the irreversible oxidative decar boxylation of isocitrate, yielding the first of three NADH molecules produced by the cycle, and the first release of C02 (see Figure 9.5). This is one of the rate-limiting steps of the TCA cycle. The enzyme is allosterically activated by ADP (a low-energy signal) and Ca, and is inhibited by ATP and NADH, whose levels are elevated when the cell has abundant energy stores. 

Isocitrate is oxidized and decarboxylated by isocitrate dehydrogenase to a-ketoglutarate, producing C02and NADH. The enzyme is inhibited by ATP and NADH, and activated by ADP and Ca++... 

Some enzymes contain bound NAD+ which oxidizes a substrate alcohol to facilitate a reaction step and is then regenerated. For example, the malolactic enzyme found in some lactic acid bacteria and also in Ascaris decarboxylates L-malate to lactate (Eq. 15-12). This reaction is similar to those of isocitrate dehydrogenase,110-112 6-phosphogluconate dehydrogenase,113 and the malic enzyme (Eq. 13-45)114 which utilize free NAD+ to first dehydrogenate the substrate to a bound oxoacid whose (3 carbonyl group facilitates decarboxylation. Likewise, the bound NAD+ of the malolactic... 

Fig. 5.22. Oxidation of acetyl-CoA via the tricarboxylic acid (TCA) cycle. Individual enzymes of the pathway are marked. 1, citrate synthase 2 and 3, cis-aconitate hydratase 4 and 3, isocitrate dehydrogenase 6, a-oxo glutarate dehydrogenas 7, succinate thiokinase 8, succinate...

Isocitrate Dehydrogenase Catalyzes the First Oxidation in the TCA Cycle a-Ketoglutarate Dehydrogenase Catalyzes the Decarboxylation of a-Ketoglutarate to Succinyl-CoA... 

Isocitrate Dehydrogenase Catalyzes the First Oxidation in the TCA Cycle... 

The first oxidative conversion of the TCA cycle is catalyzed by isocitrate dehydrogenase. This conversion takes place in two steps oxidation of the secondary alcohol to a ketone (oxalosuccinate), followed by a j8 decarboxylation to produce a-ketoglutarate (fig. 13.9). 

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. 

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