Cholesterol metabolism in dystrophic mice. II. Altered enzyme activities

In a previous study we found that free cholesterol (FC) and cholesterol ester (CE) concentrations in fast-glycolytic (FG) muscle tissue from dystrophic mice are significantly higher than normal. This increase is not due to an increased capacity for de novo cholesterol biosynthesis. HMG-CoA reductase (HMGR) (the enzyme which catalyzes the rate limiting step) activity is significantly decreased in dystrophic muscle compared to normal. This decrease is paralleled by an increased capacity for both CE production and hydrolysis, i.e., both Acyl-CoA:cholesterol acyltransferase (ACAT) activity and the activities of both lysosomal and sarcoplasmic cholesterol ester hydrolases (CEH) are greatly increased. These enzyme changes in dystrophic FG muscle are similar those observed in normal tissues with elevated levels of cholesterol, which suggests that such changes are not the cause of the altered cholesterol concentrations but are rather the response of the tissue to elevated levels of cholesterol.