Loss of feedback control of hydroxymethylglutaryl coenzyme A reductase in hepatomas

THE FEEDBACK RESPONSE OF MEVALONATE: NADP oxidoreductase (acylating CoA; EC 1.1.1.34) in two varieties of hepatoma has been examined. In marked contrast to the feedback inhibition of this enzyme that is regularly observed in normal liver, the feedback control is completely lost in minimal-deviation hepatomas 9121 and 3924A. This finding provides the first specific biochemical localization of the defect in cholesterol feedback control, which has been shown previously to be a characteristic of all hepatomas.