Phosphogluconate dehydrogenase decarboxylating

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... 

In the third step, 6-phosphogluconate is oxidatively decarboxylated to ribulose 5-phosphate in the presence of NADP+, catalyzed by 6-phosphogluconate dehydrogenase ... 

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. 

Like 6-phosphogluconate dehydrogenase and UDPglucuronate decarboxylase, this enzyme decarboxylates a /3-keto acid with an a-oxygen function without the involvement of a metal ion or other cofactor (70). Apparently the electronic properties of this oxygen function are sufficient to stabilize the enolate anion intermediate, so that no metal ion is needed. 

Oxidative decarboxylation of 6-phosphogluconate to ribulose-5-phosphate with 6-phosphogluconate-dehydrogenase and electromicrobial NADP regeneration with partially purified AMAPOR. 

The four reactions involved in this conversion are shown in figure 12.31. The first oxidation, catalyzed by glu-cose-6-phosphate dehydrogenase at C-1, converts the hemi-acetal derivative of the aldehyde group to the lactone of the corresponding acid, 6-phosphogluconic acid. After hydrolysis of the lactone, the second oxidation at C-3, converts the secondary alcohol to a ketone. The expected product, 3-keto-6-phosphogluconic acid, is decarboxylated yielding ribulose-5-phosphate. 

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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