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Dependence of the Circadian Rhythm of Hepatic β-Hydroxy-β-methylglutaryl Coenzyme A on Ribonucleic Acid Synthesis

1974; Elsevier BV; Volume: 249; Issue: 9 Linguagem: Inglês

10.1016/s0021-9258(19)42714-2

1083-351X

Peter A. Edwards, R. Gordon Gould,

Fatty Acid Research and Health

The circadian rhythm in the level of activity of rat hepatic β-hydroxy-β-methylglutaryl-CoA reductase (EC 1.1.1.34) is characterized by a rapid, 5- to 8-fold increase in activity from the basal level (9 a.m. to 4 p.m.) to a peak at midnight followed by a rapid decrease back to the basal level. In this study actinomycin D, even in high doses (400 µg/100 g), was found to have no effect on the basal enzyme level or on the rate of decline from the peak but did partially suppress the increase. Epinephrine administration during the period of basal or declining enzyme activity elicited a marked increase in reductase activity which could be prevented by concurrent actinomycin D treatment. Administration of cholesterol in corn oil by stomach tube at the time of peak reductase level produced decreases in activity 4 to 8 hours later to levels less than 50% of those in controls given oil alone. Since previous evidence indicates little or no synthesis of reductase during this period in normal rats, these results suggest that cholesterol may be stimulating the rate of breakdown or inactivation of the reductase. Cholesterol administration during the basal level period gave a 50% reduction of enzyme activity 5 hours later. Preliminary results on microsomal-free and esterfied cholesterol indicated that 4 to 7 hours after cholesterol feeding a decrease in microsomal reductase activity was correlated with an increase in the ester fraction. It is at present not clearly established whether an increase in concentration of microsomal cholesterol esters must precede the inhibition of reductase activity brought about by dietary cholesterol.