In vitro studies of lipid metabolism in human liver

To study the regulation of lipid metabolism in human liver, we have developed assay systems for three rate-determining microsomal enzymes of hepatic cholesterol metabolism: 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (regulating cholesterol biosynthesis), cholesterol 7 alpha-hydroxylase (governing bile acid formation), and acyl-CoA:cholesterol acyltransferase (ACAT; rate limiting for cholesterol esterification). In addition, we have obtained an assay for low-density lipoprotein binding to its specific receptor in human liver, and we have studied a possible rate-determining enzymatic step in triglyceride biosynthesis, cytosolic phosphatidic acid phosphatase. These assays allow us to study the effects of metabolic perturbations on hepatic lipid metabolism in humans and thus to evaluate the important role of the liver in lipoprotein synthesis and degradation.