Enamines as intermediates in enzyme catalysis

Primary amine catalysis (usually involving a lysine residue) has been recognised to play an important role in various enzyme-catalysed reactions. Examples are the conversion of acetoacetate to acetone catalysed by acetoacetate decarboxylase, the condensation of two molecules of S-aminolevulinic acid catalysed by -aminolevulinic deshydratase during the biosynthesis of porphyrins, and the reversible aldol condensation of dihydroxy-acetone phosphate with glyceraldehyde which in the presence of aldolase yields fructose-1-phosphate (64) (For reviews see, for example, Snell and Di Mari, 

1970 Shemin, 1972 Horecker et al., 1972). In these enzymatic reactions, the mechanism involves initial SchifFs base (imine) formation and subsequent tautomerisation leading to the enamine (C02 elimination in the process of acetoacetate decarboxylase). 

The above cited enzymes are usually also able to catalyse H—D exchange via enamine formation. For instance, aldolase catalyses the exchange of a C(3) hydrogen of dihydroxyphosphate (Rose and O Connell, 1969), and Westheimer and coworkers (Tagaki and Westheimer, 1968 Hammons et al., 

1975) observed that acetate decarboxylase catalyses proton exchange of acetone and 2-butanone by a mechanism similar to that suggested for bifunctional catalysis by primary amines (63). For 2-butanone, the H—D exchange at the methylene group is stereospecific as observed for dedeuteriation of 3-pentanone catalysed by [86]. 

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