The long term goal of this research is to determine in detail how various O2 oxidoreductases catalyze reactions of O2. Since these enzymes are necessary for so many metabolic pathways, including: catecholamine biosynthesis and degradation, aromatic amino acid metabolism, inositol catabolism, steroid hormone biosynthesis, drug metabolism, etc, it is felt that a more detailed understanding of their mechanisms could lead to the control or alleviation of many metabolic defects. Three specific enzymes that will be studied in the coming grant period are: Inositol Oxygenase. This kidney enzyme, which is responsible for the first step in the catabolism of inositol, and which is known to be deficient in animals with diabetes mellitus, exists in hog kidney as an enzyme complex containing also D-glucuronate reductase. Proposed experiments with the homogeneous hog kidney enzyme will be specially designed to identify intermediates in the reaction, and studies with the enzyme complex will be concerned with determining the physical and kinetic characteristics of the complex, and with exploring the possible coupling of the oxygenase and reductase activities. Diamine Oxidase. This enzyme is responsible for the metabolism of several physiologically important diamines, including putrescine, histamine, and cystamine. One set of experiments with the homogeneous hog kidney enzyme is aimed at identifying the tightly bound organic cofactor this enzyme contains, another at exploring the role of the enzyme bound copper, and a third at characterizing the oxidase catalyzed reactions of cystamine. 4-Hydroxphenylpyruvate dioxygenase. This enzyme, which participates in the metabolism of tyrosine in all animals, is involved in several metabolic diseases. Proposed experiments with the homogeneous hog liver enzyme are aimed at identifying possible intermediates in the reaction.
| Skorczynski, S S; Yang, C S; Hamilton, G A (1991) Determination of oxalyl thiolesters, N-oxalylcysteine and N-oxalylcysteamine in biological materials. Anal Biochem 192:403-10 |
| Skorczynski, S S; Mastro, A M; Hamilton, G A (1989) Oxalyl thiolester concentrations decreased in lectin and phorbol ester-stimulated lymphocytes. FASEB J 3:2415-9 |
| 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 |
