Alcohol dehydrogenase zinc-carbonyl mechanism

The major mechanistic difference between the pro-5 and the pro-/ specific enzymes in this area where thermodynamic constraints are weak or non-existent seems to be that the pro-/ specific enzymes contain a zinc ion at the active site whereas the pro-5 specific enzymes do not (Schneider-Bernlohr et al., 1986). In the mechanism of an NAD+-linked alcohol dehydrogenase shown in Scheme 6, in the reduction direction the substrate carbonyl group was shown as polarised by partial proton donation from a Bronsted acid BH + this polarisation can equally well be achieved by coordination to an active site zinc, which acts as a Lewis acid. One thus has two mechanistic classes of enzyme, but even this difference affects the stereochemistry only in a very limited region close to the break-point. 

Other Zinc Enzymes. Studies aimed at elucidating the mechanism of dimeric alcohol dehydrogenase enzymes have also been reported. Cobalt(n) can replace zinc(ii) at the two catalytic and non-catalytic sites in the liver enzyme, LADH. Reduction of pyridinealdehyde derivatives by the yeast enzyme has been examined. In acetonitrile solution, reduction by NADH analogues is catalysed by metal ions and mechanistic studies of the reaction have been carried out. Biomimetic studies of zinc-catalysed carbonyl reduction have also been reported. ... 

Alcohol dehydrogenase is one of the active enzymes in yeast. The active site in alcohol dehydrogenase contains a zinc ion, Zn, that is coordinated to the sulfur atoms of two cysteine residues of the enzyme. The hydride reducing reagent in alcohol dehydrogenase is nicotinamide adenine dinucleotide, NADH, which transfers a hydride ion to a carbonyl compound to yield an alcohol and NAD" ", in a mechanism that is related to the Cannizzaro reaction (Sec. 16.3). 

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