The overall objective of this research program is to contribute to the understanding of the molecular basis of biological processes that involve enzymes attached to intracellular membranes. We are attempting to obtain sufficient information on the structures of three enzyme components of one electron transport sequence of liver endoplasmic reticulum, which catalyzes the NADH and oxygen dependent desaturation of stearyl-CoA, and the lipid-protein interactions involved in the binding of these enzymes to microsomal vesicles to offer a detailed description of the molecular structures and interactions that govern the catalytic activities, binding and mobilities of one type of membrane-bound enzyme system. The initial renewal application for year 6 of this grant outlined the studies of primary structure of cytochrome b5 reductase as well as attempts to purify the desaturase that would be coupled with detailed investigations on the functional attachment of these enzymes to lipid vesicles, utilizing immunologic, rapid kinetic, NMR, EPR and fluorescence techniques. These objectives have direct health related implications since membranes are involved in many metabolic and regulatory cellullar functions. In particular, the fact that fatty acids have been widely implicated in hypercholesterolemia, a constant finding in atherosclerosis, emphasizes the need for information on one mechanism by which the human might regulate fatty acid desaturation as part of a comprehensive evaluation of significant factors involved in this circulatory disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM015924-20
Application #
3268865
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1978-06-01
Project End
1988-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
20
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
School of Medicine & Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030