STRUCTURE AND FUNCTION OF PEPCK CARBOXYKINASE ISOZYMES

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The goal of the research program is to study the structure, synthesis and processing of mitochondrial and cytosolic phosphoenolpyruvate carboxykinase. This will involve sequencing the enzyme protein as well as cloning a cDNA to the phosphoenolpyruvate carboxykinase mRNA using recombinant DNA procedures. Information on the structure of the enzyme will allow us to better understand its function, expecially its regulation by cofactors such as metal ions (Mn2+, Fe2+). Phosphoenolpyruvate carboxykinase is unique since, in most species, it is present in both the cytosol and mitochondria. The synthesis, transport and processing of the mitochondrial enzyme will be studied and compared to the cytosol isozyme in order to better understand the coordinate regulation of gene expression. Since phosphoenolpyruvate carboxykinase is a key, pacesetting enzyme in both hepatic and renal gluconeogenesis, our findings will contribute to a better understanding of the regulation of glucose homeostasis in verebrates and allow us to draw analogies to the regulation of both forms of the enzyme in disease processes such as diabetes.