Enzymatic ketone reduction mechanism

The Fukuzumi group later investigated the mechanism of reduction of a-haloketones using NADH model compounds [249, 250], This non-enzymatic model system was developed to investigate the role of Brpnsted acids in enzymatic ketone... 

For example, the low enantioselectivity in the yeast reduction of 3-keto ester was improved by addition of ethyl chloroacetate or methyl vinyl ketone as described in Fig. 15-13. The enzymes inhibited and those not inhibited were identified by enzymatic studies using purified enzymes [97l The mechanism of the inhibition is reported to be non-competitive. 

In the oxidation process of an alcohol by NAD+ (or NADP+), the enzymatic base positioned above the carbonyl takes back its proton, and the electrons in the O—H bond shift down and push out the hydride, which is immediately accepted by C-4 of NAD+ (or NADP+). The products are just what they were started out with, a ketone and NADH (or NADPH) (Figure 1.39). The mechanism of oxidation of amines to imines as well as of aldehyde to carboxylate is similar to the oxidation of alcohol. In the reduction process of a ketone by NADH (or NADPH), both the ketone substrate and cofactor are bound in the enzyme s active site, and C-4 of the nicotinamide ring is positioned very close to the carbonyl carbon of the ketone. As an enzymatic group transfers a proton to the ketone oxygen, the carbonyl carbon becomes more electrophilic and is attacked by a hydride from NADH (or NADPH). The ketone is reduced to an alcohol, and the NADH or NADPH cofactor is oxidized to NAD+ or... 

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