Analysis of regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in a somatic cell mutant auxotrophic for mevalonate.

Regulation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity and synthesis by 25-hydroxycholesterol is aberrant in a somatic cell mutant of the Chinese hamster ovary K1 cell auxotrophic for mevalonate by virtue of a defect in HMG-CoA synthase activity. Normal regulation of HMG-CoA reductase activity and synthesis in this mutant by 25-hydroxycholesterol can be restored by simultaneous incubation with a small (0.4 mM) mevalonate supplement. Normal regulation of HMG-CoA reductase is also observed in a revertant of the mutant cell with normal HMG-CoA synthase activity.