Short- and long-term effects of ethanol administration in vivo on rat liver HMG-CoA reductase and cholesterol 7α-hydroxylase activities

Abstract

Short- and long-term effects of ethanol on HMG-CoA reductase (EC 1.1.1.34) and cholesterol 7α-hydroxylase activities in rat liver have been investigated. Neither the reductase nor the hydroxylase activity as measured in vitro was significantly affected within 2 hr after a single intraperitoneal injection of ethanol (7 mmol per 100g body weight), whether tested at the diurnal low or the diurnal high point of activity. Although chronic ethanol feeding for 21 days did not affect the diurnal rhythm of either of these enzyme activities, it caused a 29% decrease in HMG-CoA reductase activity and a 56% decrease in cholesterol 7α-hydroxylase activity at the diurnal high point. The same chronic ethanol feeding caused a moderate increase in serum cholesterol and a significant increase in hepatic cholesterol concentration. On the basis of these findings, it is suggested that the decreased rate of cholesterol degradation to bile acids may play a significant role in the accumulation of cholesterol in the liver after chronic ethanol feeding.

Keywords

• cholesterol biosynthesis
• degradames
• rate limiting enzymes
• diurnal variation
• radiotion chemical assay