Regulation of hydroxymethylglutaryl-CoA reductase in rat leukocytes

Abstract

Methods were developed for the assay of hydroxymethylglutaryl-CoA reductase (NADPH) activity in microsomes from rat leukocytes. The activity in freshly isolated leukocytes is low compared to rat liver but can be assayed reliably. The patterns of response of leukocyte reductase in the assay to variation in substrate concentration, protein concentration, and time mimic those of rat liver reductase. Reductase activity in leukocyte microsomes, as in liver microsomes, is depressed by dietary cholesterol and by fasting and is elevated by dietary cholestyramine. Unlike liver reductase, leukocyte reductase activity does not exhibit a detectable diurnal rhythm. We conclude that the assay of reductase in freshly isolated leukocytes holds promise as a technique for detecting the effects of various factors on cholesterol synthesis in vivo.

Keywords

• cholesterol biosynthesis
• dietary cholesterol
• cholestyramine
• diurnal rhythm
• enzyme regulation
• atherogenesis