Stereochemistry in Relation to Enzyme Mechanism

Abstract

Stereochemistry was a part of enzymology long before anything was known about the chemical nature of enzymes. Stereochemistry was born in 1874, enzymes were christened in 1877; and Emil Fischer, born in 1852, was of an age to take notice of both events. When Fischer studied the action of crude ferments from seeds on derivatives of the sugars, he did not even know the correct structures of his substrates, let alone of his enzymes; but he knew which of his substrates were stereoisomers, and he could formulate his lock-and-key model of enzyme-substrate interaction as a purely stereochemical hypothesis. It is important to recognize that this hypothesis was confined to the problem of substrate specificity in enzymes. At that time (1894) there was already a secure stereochemical theory of the structures of organic molecules, a theory to which X-ray crystallography brought confirmation rather than correction; but the stereochemistry of chemical reactions was largely unknown territory. Paul Walden was doing his work on stereochemical inversion, but for four decades it was considered a curiosity outside the main stream of chemistry. Alexander McKenzie had started his work on “asymmetric syntheses”, but the stereochemical basis was supplied by Prelog more than half a century later.