Regulation of HMG-CoA reductase

Illinois State University, Normal IL

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Abstract

DESCRIPTION (provided by applicant): 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is an important enzyme found in nearly all living organisms, Its structure shows remarkable conservation between prokaryotes and eukaryotes, indicating a common evolutionary heritage. In humans, HMGR has received enormous attention in the past two decades because it is the rate-limiting step in the synthesis of cholesterol and its control by drugs (e.g., statins) has had major health benefits. However, in spite of this attention there are still major issues that need to be resolved regarding its regulation. In the studies proposed in this research application, I will study the regulation of HMGR in the mandibular organ of the lobster. Lobsters, like all other arthropods, do not synthesize cholesterol. With one less pathway using the product of HMGR, the regulation of this enzyme is likely to be less complicated. In addition, HMGR activity is very high in this tissue, since the mandibular organ produces large quantities of a sesquiterpene, methyl farnesoate. Finally, it seems likely that HMGR activity is regulated by neuroendocrine peptides. These studies may yield unique insights into the function and regulation of this enzyme.