The long-term objective of the proposed research is to delineate the biochemical reactions underlying insulin activation of acetyl CoA carboxylase (ACC), the rate-limiting enzyme for long chain fatty acid synthesis. In this proposal, two specific areas of research have been proposed: 1) cloning cDNA to ACC mRNA and 2) biochemical reactions occurring at the plasma membrane upon insulin binding. ACC is activated by insulin interaction with receptors on the plasma membrane. The product of the carboxylase reaction, i.e. malonyl CoA, directly and indirectly affects the synthesis of long chain fatty acids, triglycerides and ketone bodies. However, it is not known how this enzyme is controlled at the transcriptional level. Such studies require the methodology of molecular biology, as discussed in the first part of this research proposal. The second part of the proposed research concerns the characterization of the newly discovered insulin receptor on which insulin binds covalently. Characterization of the receptor would provide some new information as to how insulin action is mediated at the receptor level.
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