The 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) activity of rat liver microsomal fraction varies diurnally: in rats allowed to feed at will and subjected to alternate 12h periods of light and darkness the activity is maximal during the dark period and minimal during the light period (Hamprecht et al., 1969;Shapiro & Rodwell, 1971;Higgins et al., 1971). The present communication describes daily changes in this enzyme activity in rats trained to feed during the daytime; such a study seemed relevant in view of the known tendency of rats to feed during the dark (Suttie, 1968).
ExperimentalFemale Wistar rats were purchased from the Manston Research Centre, Margate, Kent, U.K., and weighed 90g. They were kept in a room artificially illuminated between 09:00h and 21:00h, and in darkness between 21 :00h and 09:00h. Control animals were allowed continuous access to food, but test rats were fed from 09:00h to 12:00h each day. (All times quoted here refer to British Summer Time, which is 1 h ahead of Greenwich Mean Time.) Water was accessible at all times. Animals were maintained for 10 days before the experiment, and, beginning at 24:00h of day 10, measurements of enzyme activity were made; at 09:00h some of the test rats were fed as usual but others were given no food.Liver microsomal fraction was prepared as described by Tata (1969). Enzyme activity was measured by incubating microsomal preparations with 3-hydroxy-3-methyl[3-14C]glutaryl-CoA (specific radioactivity 0.60,uCi/p,mol) and a system for
Dietary cholesterol lowers the activity of rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase without affecting various other liver microsomal enzymes. This is consistent with a specific regulatory mechanism and distinguishes the action of cholesterol on 3-hydroxy-3-methylglutaryl-CoA reductase from that of at least one other stimulus known to affect this enzyme.
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