Several lines of research in this laboratory have recently converged to suggest that oxalyl thioesters (RSCOCOO-) may plan an important role in controlling metabolism in animals, and may function as mediators for some hormones, especially insulin. If oxalyl thioesters are functioning in this way then obviously they must modify the catalytic activities of various enzymes, and preliminary results with a few systems indicate that to be the case. In order to evaluate how important a system of metabolic control based on oxalyl thioesters might be, it will be necessary to characterize more thoroughly their effects on these as well as other enzymes. That is the general goal of the proposed research. The effects of oxalyl thioesters on several of the following animal enzymes will be investigated: protein phosphatases, malic enzyme, succinyl CoA transferase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, hexokinase, fructose-1,6-diphosphatase, isocitrate dehydrogenase, Na/K ATPase, etc. Initially the effect of oxalyl thioester structure, concentration and time of incubation with enzyme will be studied but eventually the detailed mechanism for any enzyme modifications will be investigated. The research potentially could lead to the elucidation of a whole new system of metabolic control in animals. Not only may it be particularly relevant to the insulin related disease, diabetes, but also to diseases such as cancer, since various growth factors and protein products of oncogenes seem closely related to insulin.
|Hamilton, G A; Buckthal, D J; Kantorczyk, N J et al. (1988) S-oxalylglutathione is a substrate for gamma-glutamyltransferase (GGT). Implications for the role of GGT in cell proliferation. Biochem Biophys Res Commun 150:828-34|