1. Establish the metabolic pathways of polyprenol synthesis by isolating and characterizing other prenyltransferases and to determine the role of the farnesyl-PP synthetase in the synthesis of dolichols and coenzyme Q. Measure the concentration of key metabolites of sterol and polyprenol synthesis in normal tissue and in tissues in which the rate of cholesterol synthesis has been perturbed. 2. Determine the turnover of prenyltransferase in normal tissues and cells as well as in tissues and cells in which the rate of cholesterol synthesis has perturbed. Determine the relative amounts of active and inactive forms of this enzyme under the above conditions and evaluate the significance of the active and inactive forms, especially in the neonate. 3. Evaluate the mechanism by which the diet of the neonate changes the mode of regulation of cholesterol biosynthesis in the adult.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM013140-24
Application #
3150848
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1977-07-01
Project End
1987-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
24
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Kuswik-Rabiega, G; Rilling, H C (1987) Squalene synthetase. Solubilization and partial purification of squalene synthetase, copurification of presqualene pyrophosphate and squalene synthetase activities. J Biol Chem 262:1505-9
Bruenger, E; Rilling, H C (1986) Prenylated proteins from kidney. Biochem Biophys Res Commun 139:209-14
Bruenger, E; Chayet, L; Rilling, H C (1986) Isopentenyl pyrophosphate isomerase:dimethylallyl pyrophosphate isomerase: isolation from Claviceps sp. SD 58 and comparison to the mammalian enzyme. Arch Biochem Biophys 248:620-5
Bruenger, E; Rilling, H C (1986) Prenyltransferase and squalene synthetase in livers of neonate rats. Biochim Biophys Acta 876:500-6
Rilling, H C (1985) Photoaffinity substrate analogs for eukaryotic prenyltransferase. Methods Enzymol 110:125-30
Rilling, H C (1985) The mechanism of the condensation reactions of cholesterol biosynthesis. Fourth Morton lecture. Biochem Soc Trans 13:997-1003
Rilling, H C (1985) Eukaryotic prenyltransferases. Methods Enzymol 110:145-52