Isocitric acid dehydrogenase function

The enzyme isocitrate dehydrogenase is one of the enzymes of the Krebs or citric acid cycle, a major feature in carbohydrate metabolism (see Section 15.3). This enzyme has two functions, the major one being the dehydrogenation (oxidation) of the secondary alcohol group in isocitric acid to a ketone, forming oxalosuccinic acid. This requires the cofactor NAD+ (see Section 11.2). For convenience, we are showing non-ionized acids here, e.g. isocitric acid, rather than anions, e.g. isocitrate. 

The second function, and the one pertinent to this section, is the decarboxylation of oxalosuccinic acid to 2-oxoglutaric acid. This is simply a biochemical example of the ready decarboxylation of a P-ketoacid, involving an intramolecular hydrogen-bonded system. This reaction could occur chemically without an enzyme, but it is known that isocitric acid, the product of the dehydrogenation, is still bound to the enzyme isocitrate dehydrogenase when decarboxylation occurs. 

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. 

There are two different forms of isocitrate dehydrogenase in all cells, one requiring NAD+ as electron acceptor and the other requiring NADP+. The overall reactions are otherwise identical. In eukaryotic cells, the NAD-dependent enzyme occurs in the mitochondrial matrix and serves in the citric acid cycle. The main function of the NADP-dependent enzyme, found in both the... 

It is highly probable that the Krebs cycle functions in all cells. Several reports have implied that it does not exist in the skin either because some enzymes essential to its performance could not be found in skin homogenate or because oxygen uptake was not stimulated by the addition of various substrates such as citrate or a-ketoglutarate to the skin slices. However, these first conclusions were followed by contradictory observations a-ketoglutarate and other substrates were later found to stimulate oxygen uptake, and two enzymes of the citric acid cycle—malic isocitrate and succinic dehydrogenase—were detected in rat skin. 

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