Ascorbic acid regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol synthesis in guinea pig liver.
Guinea pigs fed a normal diet show the expected diurnal variation in 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Vitamin C deficiency, however, suppresses the diurnal peak activity of reductase, due to a decrease in active (unphosphorylated) enzyme. Inhibition of reductase is paralleled by both a fall in hepatic cholesterol synthesis and a rise in serum cholesterol. Incubation of normal guinea pig hepatic microsomes with physiologic and supraphysiologic concentrations of sodium ascorbate also leads to a concentration-dependent inhibition of reductase activity. Thus, dietary extremes of vitamin C may exert similar effects on reductase activity and cholesterolgenesis. Moreover, the changes in enzyme activity induced by ascorbic acid appear to be due in part to a direct effect of the vitamin on the microsomally bound enzyme.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001206:Ascorbic Acid Deficiency / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D002940:Circadian Rhythm; D006168:Guinea Pigs; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation
D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D001205:Ascorbic Acid