Study of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in Cultured Fibroblasts from Normal and Type II Hyperlipoproteinemic Individuals
Heinrich, Mary Beth
MetadataShow full item record
The homozygous form of the autosomal dominant disease Type II hyperlipoproteinemia is characterized by elevated levels of cholesterol in the bloodstream. Cultured skin fibroblasts from a patient with this disorder showed higher activity levels of the rate limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, than in fibroblasts from a normal individual. Work with normal fibroblast cells revealed strong inhibition and feedback control of the enzyme's activity by low density lipoprotein, the major cholesterol-carrying lipoprotein in the human bloodstream. This feedback control on cholesterol synthesis appears to be lacking in Type II hyperlipoproteinemia. Lipoprotein-free serum was shown to greatly increase 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in all cells studied, and experiments were conducted to isolate the factor responsible for this elevation. In addition, certain experimental conditions were standardized with normal cells to facilitate future study of homozygous and heterozygous Type II hyperlipoproteinemia cell lines.