Isocitric dehydrogenase and

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.

M. Lancien, S. Ferrario-Mery, Y. Eoux, E. Bismuth, C. Ma.sclaux, B. Hirel, P. Gadal, and M. Hodges, Simultaneous expression of NAD-dependent isocitrate dehydrogenase and other Krebs cycle genes after nitrate resupply to short-term nitrogen starved tobacco. Plant Physiol. 120 1X1 (1999). 

K8. Kerppola, W., Nikkila, E. A., and Pitkanen, E., Serum TPN linked enzymes glucose-6-phosphate dehydrogenase, isocitric dehydrogenase and glutathione reductase activities in health and various disease states. Acta Med. Scand. 164, 357-305 (1959). 

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). 

Citrate synthase, isocitrate dehydrogenase and oxogluta-rate dehydrogenase are key enzymes regulating the flux through the cycle all three catalyse non-equilibrium reactions (Chapter 3). 

It increases the activity of isocitrate dehydrogenase and oxoglntarate dehydrogenase and hence the flux through the cycle. 

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. 

Fig. 1 Enzymes localized to B. hominis mitochondrial-like organelle. The enzymes are 1 malic enzyme, 2 pyruvate NADP oxidoreductase, 3 acetate succinate CoA transferase, 4 succinate thiokinase, 5 a-ketoglutarate dehydrogenase, 6 isocitrate dehydrogenase, and 7 aconitase...

The overall rate of the citric acid cycle is controlled by the rate of conversion of pyruvate to acetyl-CoA and by the flux through citrate synthase, isocitrate dehydrogenase, and a-lcetoglutarate dehydrogenase. These fluxes are largely determined by the concentrations of substrates and products the end products ATP and NADH are inhibitory, and the substrates NAD+ and ADP are stimulatory. 

Expands and updates the presentation of the mechanism for pyruvate carboxylase. Adds coverage of the mechanisms of isocitrate dehydrogenase and citrate synthase. 

The effect of small-molecule modifiers on isocitrate dehydrogenase is appropriate in that a high-energy charge favors inhibition of isocitrate dehydrogenase and thus favors an accumulation of mitochondrial citrate. This leads to an increased flow of citrate from the mitochondrion to the cytosol where the citrate can exert its multiple positive effects on biosynthesis and its negative effects on glycolysis. 

ADP, acetyl-CoA, succinyl-CoA, and citrate. The major known sites for regulation of the cycle include two enzymes outside the cycle (pyruvate dehydrogenase and pyruvate carboxylase) and three enzymes inside the cycle (citrate synthase, isocitrate dehydrogenase, and a-ketoglutarate dehydrogenase). All of these sites of regulation represent important metabolic branchpoints. 

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

T Yaoi, K Miyazaki, T Oshima. Substrate recognition of isocitrate dehydrogenase and 3-isopropylmalate dehydrogenase from Thermus thermophilus HB8. J Biochem 121 78-81, 1997. 

GA Rutter, RM Denton. The binding of Ca2+ ions to pig heart NAD+-isocitrate dehydrogenase and the 2-oxoglutarate dehydrogenase complex. Biochem J 263 453-462, 1989. 

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... 

For example, if a 10-mL solution containing isocitrate and isocitrate dehydrogenase and NADP+ exhibits a 0.04 change in the absorbance in 2 min., the enzyme activity will be... 

To measure the activity of an enzyme of the citric acid cycle, isocitrate dehydrogenase, and the effect of enzyme concentration on the rate of reaction. 

Labeling of NADPH and citric acid from incubation of citric acid, aconitase, isocitrate dehydrogenase and NADP in 85% 2H2Oa... 

Rakhmanova, T.I., Popova, T.N. (2006). Regulation of 2-oxoglutarate metabolism in rat liver by NADP-isocitrate dehydrogenase and aspartate aminotransferase. Biochemistry (Mosc.) 71(2) 211-17. 

The rate of the citric acid cycle is precisely adjusted to meet an animal cell s needs for ATP (Figure 1718). The primary control points are the allosteric enzymes isocitrate dehydrogenase and a-ketoglutarate dehydrogenase. 

Figure 17.18. Control of the Citric Acid Cycle. The citric acid cycle is regulated primarily by the concentration of ATP and NADH. The key control points are the enzymes isocitrate dehydrogenase and a-ketoglutarate dehydrogenase.

---