Malate isocitrate dehydrogenase

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. 

Balance Sheet for the Citric Acid Cycle The citric acid cycle has eight enzymes citrate synthase, aconitase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, succinyl-CoA synthetase, succinate dehydrogenase, fumarase, and malate dehydrogenase. 

Compartmentalization of Citric Acid Cycle Components Isocitrate dehydrogenase is found only in the mitochondrion, but malate dehydrogenase is found in both the cytosol and mitochondrion. What is the role of cytosolic malate dehydrogenase ... 

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... 

To understand why isocitrate dehydrogenase is so intensely regulated we must consider reactions beyond the TCA cycle, and indeed beyond the mitochondrion (fig. 13.15). Of the two compounds citrate and isocitrate, only citrate is transported across the barrier imposed by the mitochondrial membrane. Citrate that passes from the mitochondrion to the cytosol plays a major role in biosynthesis, both because of its immediate regulatory properties and because of the chain of covalent reactions it initiates. In the cytosol citrate undergoes a cleavage reaction in which acetyl-CoA is produced. The other cleavage product, oxaloacetate, can be utilized directly in various biosynthetic reactions or it can be converted to malate. The malate so formed can be returned to the mitochondrion, or it can be converted in the cytosol to pyruvate, which also results in the reduction of NADP+ to NADPH. The pyruvate is either utilized directly in biosynthetic processes, or like malate, can return to the mitochondrion. 

Fig. 1.2 Intermediates of the citric acid cycle showing the relationship between glutamate and aspartate. Pyruvate dehydrogenase complex (1) citrate synthase (2) aconitase (3) isocitrate dehydrogenase (4) a-ketoglutarate dehydrogenase (5) succinyl-CoA synthetase (6) fumarate (7) fumarase dehydratase (8) malate dehydrogenase (9) and aspartate aminotransferase (10)...

Oxidation of reduced pyridine nucleotides Reaction with isocitrate dehydrogenase, glucose 6-phosphate dehydrogenase, malate dehydrogenase Reaction with GSH... 

This methodology was applied to calculate the relative binding free energy of 63 pairs of nine different mutant proteins with seven substituted R-malate substances of Escherichia Coli isocitrate dehydrogenase. The average difference for the calculated and the observed relative binding difference was 0.5kcal/mol.47... 

Fluorimetric methods involving six dehydrogenases have been used to determine the concentrations of 21 of the more common organic acids (58). Sensitivity of the methods range from 0.02 fxg/m for determination of D-isocitric acid with isocitrate dehydrogenase to 200 /xg/ml for determination of D-tartaric acid with malate dehydrogenase. 

Enzymes (malate dehydrogenase, lactate dehydrogenase, isocitrate dehydrogenase, citrate lyase)... 

Niacin is utilized in the synthesis of the nicotinamide portion of NAD, which is used in the isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, and malate dehydrogenase reactions. 

NADH is produced by the a-ketoglutarate dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase reactions of the TCA cycle, by the pyruvate dehydrogenase reaction that converts pyruvate to acetyl CoA, by (3-oxidation of fatty acids, and by other oxidation reactions. 

D. Pyruvate dehydrogenase and a-ketoglutarate dehydrogenase require four vitamins for synthesis of their coenzymes (thiamine, pantothenate, niacin, and riboflavin). Niacin is also required for the NAD+ utilized by isocitrate dehydrogenase and malate dehydrogenase. Riboflavin is required for the FAD utilized by succinate dehydrogenase and the FMN of the electron transport chain. Biotin is not required. 

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