Abstract

The overall goal of the program is to elucidate the mechanisms of regulation of cholesterol homeostasis in the liver. Major emphasis is on the regulation of cholesterol esterification by the enzyme acyl coenzyme A: cholesterol acyltransferase (ACAT). This proposal is aimed at preparation of specific antibodies to ACAT in order to study the detailed regulation of this enzyme at the molecular, biochemical and physiological levels. Kinetic analyses of microsomal ACAT will be used to gain information on the relative importance of different modes of regulation of the enzyme. The antibodies will be used to examine regulation of ACAT by synthesis, degradation, phosphorylation; to investigate subcellular localization of ACAT in the liver and its localization in the intestine; and to study the molecular biology of the enzyme. These studies, by describing how cholesterol esterification in the liver is regulated, may help us to understand the pathologies of both atherosclerosis and cholelithiasis and may enable us to devise rational means of preventing or alleviating these diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038553-02
Application #
3237957
Study Section
Metabolism Study Section (MET)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Smith, J L; Lear, S R; Forte, T M et al. (1998) Effect of pregnancy and lactation on lipoprotein and cholesterol metabolism in the rat. J Lipid Res 39:2237-49
Spencer, T A; Clark, D S; Johnson, G A et al. (1997) Feasibility of an immunoassay for mevalonolactone. Bioorg Med Chem 5:873-82
Erickson, S K; Van Zuiden, P E (1995) Effects of bile salts on rat hepatic acyl CoA:cholesterol acyltransferase. Lipids 30:911-5
Smith, J L; Lear, S R; Erickson, S K (1995) Developmental expression of elements of hepatic cholesterol metabolism in the rat. J Lipid Res 36:641-52
Erickson, S K; Lear, S R; McCreery, M J (1994) Functional sizes of hepatic enzymes of cholesteryl ester metabolism determined by radiation inactivation. J Lipid Res 35:763-9
Engler, M M; Engler, M B; Erickson, S K et al. (1992) Dietary gamma-linolenic acid lowers blood pressure and alters aortic reactivity and cholesterol metabolism in hypertension. J Hypertens 10:1197-204
Erickson, S K; Lear, S R; Barker, M E et al. (1990) Regulation of cholesterol metabolism in the ethionine-induced premalignant rat liver. J Lipid Res 31:933-45
Ozasa, S; Kempner, E S; Erickson, S K (1989) Functional size of acyl coenzyme A:diacylglycerol acyltransferase by radiation inactivation. J Lipid Res 30:1759-62
Erickson, S K; Jaeckle, S; Lear, S R et al. (1989) Regulation of hepatic cholesterol and lipoprotein metabolism in ethinyl estradiol-treated rats. J Lipid Res 30:1763-71