Dehydrogenase isocitrate

AceCyl-CoA + oxaloacetate + HgO. CoASH + citrate 2. Citrate. isocitrate 3. Isocitrate + NAD. a-ketoglntarate + NADH + CO, + 4. a-Ketoglntarate + CoASH + NAD. snccinyl-CoA + NADH + CO, + H Citrate synthase Aconitase Isocitrate dehydrogenase u-Ketoglutarate dehydrogenase complex... 

Isocitrate Dehydrogenase Links the TCA Cycle and Electron Transport... 

FIGURE 20.10 (a) The isocitrate dehydrogenase reaction, (b) The active site of isocitrate dehydrogenase. Isocitrate is shown in green, NADP is shown in gold, with Ca" in red. 

It may seem surprising that isocitrate dehydrogenase is strongly regulated, because it is not an apparent branch point within the TCA cycle. However, the citrate/isocitrate ratio controls the rate of production of cytosolic acetyl-CoA, because acetyl-CoA in the cytosol is derived from citrate exported from the mitochondrion. (Breakdown of cytosolic citrate produces oxaloacetate and acetyl-CoA, which can be used in a variety of biosynthetic processes.) Thus, isocitrate dehydrogenase activity in the mitochondrion favors catabolic TCA cycle activity over anabolic utilization of acetyl-CoA in the cytosol. 

The serine residue of isocitrate dehydrogenase that is phos-phorylated by protein kinase lies within the active site of the enzyme. This situation contrasts with most other examples of covalent modification by protein phosphorylation, where the phosphorylation occurs at a site remote from the active site. What direct effect do you think such active-site phosphorylation might have on the catalytic activity of isocitrate dehydrogenase (See Barford, D., 1991. Molecular mechanisms for the control of enzymic activity by protein phosphorylation. Bioehimiea et Biophysiea Acta 1133 55-62.)... 

This is the isocitrate dehydrogenase reaction of the TCA cycle. Writing the two half-cell reactions, we have... 

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. 

Enzymes a) citrate synthase b) aconitase c) isocitrate dehydrogenase d) a-oxoglutarate dehydrogenase e) succiny CoA synthetase f) succinate dehydrogenase g) fumarase h) malate dehydrogenase i) nucleoside diphosphokinase. 

Figure 5.3 Major control points of glycolysis and the TCA cycle. Enzymes I, hexokinase II, phosphofructokinase III, pyruvate kinase IV, pyruvate dehydrogenase V, citrate synthase VI, aconitase VII, isocitrate dehydrogenase VIII, a-oxoglutarate dehydrogenase.

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 undergoes dehydrogenation catalyzed by isocitrate dehydrogenase to form, initially, oxalosucci-nate, which remains enzyme-bound and undergoes decarboxylation to a-ketoglutarate. The decarboxylation... 

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.

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). 

Several mutant strains of R. eutropha that were made to possess defective competing metabolic pathways with the PHA biosynthetic pathway were developed for the enhanced PHA production. The isocitrate dehydrogenase leaky mutant of R. eutropha accumulated P(3HB) more favorably at a lower car-bon/nitrogen molar ratio and at a lower carbon concentration than the parent strain [82]. In batch culture, the final cell and P(3HB) concentrations, and P(3HB) yield on glucose were slightly increased. Also, in the P(3HB-co-3HV) biosynthesis, the molar fraction of 3HV and the 3HV yield on propionic acid increased due to the enhanced conversion of propionic acid to 3-hydroxyvaleryl-CoA rather than to acetyl-CoA and C02 in this mutant. Another mutant R. eu-... 

Colman, R.F. (1969) The role of sulfhydryl groups in the catalytic function of isocitrate dehydrogenase. I. Reaction with 5,5 -dithiobis(2-nitrobenzoic acid). Biochemistry 8, 888. 

Mn deficit Biogeochemical provinces in different regions of biosphere Lowering content of Mn in soils and plant species Reducing Mn content in bones. Decreasing activity of phosphatase, phosphorilase, and isocitric dehydrogenase... 

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). 

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