Tricarboxylic acid cycle isocitrate dehydrogenase

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... 

The second metabolic pathway which we have chosen to describe is the tricarboxylic acid cycle, often referred to as the Krebs cycle. This represents the biochemical hub of intermediary metabolism, not only in the oxidative catabolism of carbohydrates, lipids, and amino acids in aerobic eukaryotes and prokaryotes, but also as a source of numerous biosynthetic precursors. Pyruvate, formed in the cytosol by glycolysis, is transported into the matrix of the mitochondria where it is converted to acetyl CoA by the multi-enzyme complex, pyruvate dehydrogenase. Acetyl CoA is also produced by the mitochondrial S-oxidation of fatty acids and by the oxidative metabolism of a number of amino acids. The first reaction of the cycle (Figure 5.12) involves the condensation of acetyl Co and oxaloacetate to form citrate (1), a Claisen ester condensation. Citrate is then converted to the more easily oxidised secondary alcohol, isocitrate (2), by the iron-sulfur centre of the enzyme aconitase (described in Chapter 13). This reaction involves successive dehydration of citrate, producing enzyme-bound cis-aconitate, followed by rehydration, to give isocitrate. In this reaction, the enzyme distinguishes between the two external carboxyl groups... 

Figure 3.7. Specific activities of the tricarboxylic acid cycle enzymes in P. shermanii (A) and P. petersonii (B) grown imder aerobic conditions (a), stationary conditions (b), or anaerobic conditions (c). 1 isocitrate dehydrogenase 2 aconitase 3 a-ketoglutarate dehydrogenase 4 citrate synthase 5 succinate thiokinase 6 succinate dehydrogenase 7 fumarase 8 malate dehydrogenase. From Krainova and Bonarceva (1973).

Fig. 5.3 Examples of connections between epigenetics and metabolic pathways. (Abbreviations a-KT a-ketoglutarate AcCoA acetyl coenzyme A AcsCSl acetyl-CoA synthase 1 ACL ATP-citrate lyase ETC electron-transport chain FAD flavin adenine dinucleotide GSH glutathione IDH isocitrate dehydrogenase LDH lactate dehydrogenase NAD nicotinamide adenine dinucleotide SAM5-adenosyl methionine TCA tricarboxylic acid cycle)...

Phosphorylation of an enzyme can affect catalysis in another way by altering substrate-binding affinity. For example, when isocitrate dehydrogenase (an enzyme of the citric acid cycle Chapter 16) is phospho-rylated, electrostatic repulsion by the phosphoryl group inhibits the binding of citrate (a tricarboxylic acid) at the active site. 

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...

Fig. 2.7. Tricarboxylic acid or Krebs cycle. 1 = citrate synthase 2-3 = aconitase 4 = isocitrate dehydrogenase 5 = complex a-ketoglutarate dehydrogenase 6 = snccinyl-CoA synthetase, 7 = succinate dehydrogenase 8 = fumarase 9 = malate dehydrogenase GTP = guanosine triphosphate GDP = guanosine diphosphate...

PHB synthesis from glucose using Azotobacter beijerinkii revealed substantial amounts of polymer accumulation under oxygen limitation conditions. The key feature of control in A. beijerinckii is the pool size of acetyl-CoA, which may either be oxidized via the tricarboxylic acid (TCA) cycle or can serve as a substrate for PHB synthesis the diversion depends on environmental conditions, especially oxygen limitation, when the NADH/NAD ratio increases. Citrate synthase and isocitrate dehydrogenase are inhibited by NADH, and as a consequence, acetyl-CoA no longer enters the TCA cycle at the same rate. Instead acetyl-CoA is converted to acetoacetyl-CoA by p-ketothiolase, the first... 

It is generally accepted that only NADPH would be able to supply the hydrogen necessary for lipogenesis in the condensation system (Lynen, 1961 Ball, 1966). Lowenstein, therefore, has suggested another pathway for the formation of NADPH in the cytoplasm (Lowenstein, 1961b). It is dependent on the capacity of the cytoplasm to accomplish the first reactions of the tricarboxylic cycle, i.e., the reactions that yield a-ketoglutaric acid. A cytoplasmic NADP-isocitrate dehydrogenase, in contrast to the mitochondrial enzyme, the coen-... 

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