Malic enzyme 6-phosphogluconate 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... 

NADPH, which provides the reducing equivalents for fatty acid synthesis, is produced by the inducible malic enzyme and by the inducible enzymes of the pentose phosphate pathway, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. 

Keto-6-phosphogluconate is a probable intermediate. The reaction is similar to those catalyzed by malic enzyme (in gluconeogenesis) and by isocitrate dehydrogenase (in the TCA cycle). 

A variety of enzymes catalyze the oxidative decarboxylation of jS-hydroxy acids. Isotope effect studies of malic enzyme (29), isocitrate dehydrogenase (63), and 6-phosphogluconate dehydrogenase (64) indicate that all three of these oxidative decarboxylations occur by stepwise mechanisms in which hydride transfer occurs first, forming a j3-keto acid that then undergoes decarboxylation. Hydride transfer and decarboxylation are both partially rate determining. 

Glucose 6-phosphate dehydrogenase 6-Phosphogluconate dehydrogenase Pyruvate dehydrogenase Acetyl-CoA carboxylase Malic enzyme ATP-cItrate lyase Fatty acid synthase complex Stearoyl-CoA dehydrogenase Acyl-CoA-glycerol transferases... 

Glucose-6-P and 6-phosphogluconate dehydrogenases [46-51] of the hexose monophosphate shunt (A, Fig. 2) and malic enzyme [50-55] of the malate transhydrogenation cycle (B, Fig. 2) appear to be regulated both by variations in tissue levels and by metabolite effectors. The details of the regulation of these pathways are beyond the scope of this chapter. 

After oxidation, the phosphogluconic acid undergoes decarboxylation. In this reaction catalyzed by 6-phos-phogluconate dehydrogenase, as in that catalyzed by the malic enzyme, no free intermediate has been detected, and, again, the reaction presumably occurs on a single protein. The oxidative carboxylation is NADP-dependent and yields D-ribulose-5-phosphate, CO2, and NADPH as final products. This is the only step in the cycle in which CO2 is formed. 

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