Enzymatic conversion of a delta-4-3-ketosteroid into a 3-alpha-hydroxy-5-beta steroid: mechanism and stereochemistry of hydrogen transfer from NADPH. Bile acids and steroids 190.

Abstract

The conversion of [4‐14C]7α, 12α‐dihydroxycholest‐4‐en‐3‐one into 5β‐cholestane‐3α,7α,12α‐triol, catalyzed by Δ4‐3‐ketosteroid 5β‐reductase and 3α‐hydroxysteroid dehydrogenase from rat liver, has been studied in the presence of tritiated water and NADPH labeled with tritium in the A‐ and B‐positions. It was concluded that the reduction of the Δ4 double bond involves a direct hydride ion transfer from the A‐position of NADPH to the 5β‐position of the steroid and the addition of a proton to the 4‐position of the steroid. The reduction of the 3‐keto group was found to involve a direct transfer of hydrogen from the A‐position of NADPH to the 3β‐position of the steroid.