Enzymes of carbohydrate metabolism: The well-known major pathways of carbohydrate metabolism employ phosphorylated substrates such as glucose-6-phosphate. I am interested in determining the metabolic roles for enzymes that catalyze the oxidation of non-phosphorylated hexoses and pentoses. Some are already known, e.g. aldose reductase and L-iditol dehydrogenase in seminal vesicles combine to convert D-glucose to the D-fructose found in semen. Glucose (hexose-6-phosphate) dehydrogenase, an enzyme of the microsomal fractions of vertebrate livers, may be functional within these membrane systems.The physiological function of another enzyme, L-fucose (D-arabinose) dehydrogenase is unclear. My plans for research on these enzymes include: 1. investigation of in situ microsomal glucose utilization using 14C-hexose substrates; 2. purifying enzymes involved in the observed glucose oxidation for study of their physical properties and primary structures; 3. doing a comparative study of these enzyme activities in animals at various stages of the phylogenic tree.
Diabetes mellitus: This disease is one of the leading causes of blindness, atherosclerosis, and kidney failure; these and other pathological conditions are called “complications of diabetes.” Organs from diabetic animals possess certain enzyme activities, including acid hydrolase activities, in levels that are significantly different from nondiabetic (normal) controls; these changes also occur in human subjects. I am interested in finding out if abnormal levels of certain acid hydrolases are directly connected with the development of diabetic complications. My plans for continued research in this area include: 1. study of the effect of diabetes on additional acid hydrolases, with experimental determination of whether any changes from normal values in diabetic subjects are caused by lack of enzyme synthesis or by inhibition of a given acid hydrolase; 2. test diabetic and normal tissue for concentrations of substances known to be substrates of enzymes whose level of activity is abnormal in organs from diabetic subjects.
Protein-browning (Maillard) reactions: Once only food chemists were interested in studying protein-browning reactions, but now we realize that these reactions also occur under physiological conditions. Browning begins with the nonenzymatic reaction of monosaccharides with protein primary amine groups; this is the basis of a diagnostic test for the effectiveness of treatment given diabetic patients. Some believe that further reactions of the glucosylated proteins yield products that lead to development of some of the complications of diabetes mellitus. My research interest in this area includes: 1. identification of the actual products formed by reaction of glucosylated proteins; 2. study of the mechanism of browning reactions, currently emphasizing a study of possible free radical involvement; 3. determination of the kinetics by which various Maillard reactions occur, which will inform the development of a computer simulation of protein browning over long time periods under physiological conditions.
