Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase

Breaking a carbon–hydrogen bond adjacent to a carbonyl is a slow step in a large number of chemical reactions. However, many enzymes are capable of catalyzing this reaction with great efficiency. One of the most proficient of these enzymes is 3-oxo-Δ5-steroid isomerase (KSI), which catalyzes the isomerization of a wide variety of 3-oxo-Δ5-steroids to their Δ4-conjugated isomers. In this review, the mechanism of KSI is discussed, with particular emphasis on energetic considerations. Both experimental and theoretical approaches are considered to explain the mechanistic details of the reaction.