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. [ABSTRACT FROM AUTHOR]