The Stereochemistry of Hydrogen Transfer from NADPH Catalysed by 3‐Hydroxy‐3‐methylglutaryl‐coenzyme A Reductase from Rat Liver

3‐Hydroxy‐3‐methyl‐[3‐14C]glutaryl‐CoA was reduced to mevalonic acid in the presence of either [4A‐3H]‐ or [4B‐3H]NADPH and rat liver 3‐hydroxy‐3‐methylglutaryl‐CoA reductase. The resulting doubly labelled mevalonic acid incorporated tritium exclusively from the 4A (4R) position of NADPH. The distribution of tritium at C‐5 of the mevalonic acid was determined by a biological degradation. It was concluded that during the reduction of 3‐hydroxy‐3‐methylglutaryl‐CoA to mevalonic acid two hydrogen atoms from the 4A (4R) position of NADPH are transferred directly to mevalonic acid.