Isocitrate dehydrogenase stereochemistry

In leucine biosynthesis, the intermediate 218 on the valine pathway reacts with acetyl-CoA to yield a-isopropylmalate 225 whose configuration has been shown to be S by X-ray crystallography (200). This reaction is analogous to that catalyzed by citrate synthase, and indeed the subsequent reaction, dehydration/rehydration giving ) -isopropylmalate 226, is analogous to the conversion of citrate to isocitrate. The configuration of / -isopropylmalate 226 had been shown to be 2i ,3S (201), and so the stereochemistry of the citrate and isopropylmalate reactions was identical. j -Isopropylmalate 226 was finally converted to leucine 205 by a 4-pro-R NADH specific dehydrogenase (EC 1.1.1.85) (202) and transamination (Scheme 61). 

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