PubMed Health⌕ Search

Biomedical subjects

J R Godin

Publications and source records attributed to J R Godin.

8 recordsLinked to original sources
PubMed1988

Comparative studies of glutathione reductase and lipoamide dehydrogenase.

1. Glutathione reductase and lipoamide dehydrogenase are structurally and mechanistically related flavoenzymes catalyzing various one and two electron transfer reactions between NAD(P)H and substrates with different structures. 2. The two enzymes differ in their coenzyme and functional specificities. Lipoamide dehydrogenase shows higher coenzyme preference while glutathione reductase displays greater functional specificity. 3. Binding preference of the two flavoenzymes for nicotinamide coenzymes is demonstrated by 31P-NMR spectroscopy. 4. The presence of arginines in glutathione reductase which is inactivated by phenyl glyoxal, is likely to be responsible for the NADPH-activity of glutathione reductase. 5. The substrate binding sites of the two enzymes are similar, though their functional details differ. 6. The active-site histidine of glutathione reductase functions primarily as the proton donor during catalysis. While the active-site histidine of lipoamide dehydrogenase stabilizes the thiolate anion intermediate and relays a proton in the catalytic process.

Animals↗
PubMed1987

Multifunctional activities of yeast glutathione reductase.

Yeast glutathione reductase exists in a single molecular form which exhibits preferred NADPH and weak NADH linked multifunctional activities. Kinetic parameters for the NADPH and NADH linked reductase, transhydrogenase, electron transferase and diaphorase reactions have been determined. The functional preference for the NADPH linked reductase reaction is kinetically related to the high catalytic efficiency and low dissociation constants for substrates. NADP+ and NAD+ may interact with two different sites or different kinetic forms of the enzyme. The active site disulfide and histidine are required for the reductase activity but are not essential to the transhydrogenase, electron transferase and diaphorase activities. Amidation of carboxyl groups and Co(II) chelation of glutathione reductase facilitate the electron transferase reaction presumably by encouraging the formation of an anionic flavosemiquinone.

Binding Sites↗
PubMed1985

Dye-sensitized photo-oxidation of enzymes.

Heart lipoamide dehydrogenase, liver alcohol dehydrogenase and egg-white lysozyme are photo-oxidized in the presence of various dye sensitizers. The photodynamic process is preceded by the binding between the enzyme and the sensitizers. Among the commonly used dyes, halogenated xanthines and thiazine are effective sensitizers for the photo-inactivation of these three enzymes. Histidine residues are the primary target for the sensitized photo-oxidation that inactivates lipoamide dehydrogenase and alcohol dehydrogenase. However, the destruction of tryptophan residues is responsible for the photo-inactivation of lysozyme. The deuterium medium effect and the quenching effect by various scavengers of the potential photo-oxidative intermediates implicate the participation of the mixed type I-type II mechanism, with the involvement of singlet oxygen being of greater importance, in the photo-inactivation of the enzymes.

Alcohol Dehydrogenase↗
PubMed1981

Triazene metabolism. I. The effect of substituents in the aryl group on the kinetics of enzyme-catalysed N-demethylation of 1-aryl-3,3-dimethyltriazenes.

A series of antitumor dimethylaryltriazenes (ArN==N . NMe2) have been studied with respect to enzyme catalysed N-demethylation by liver microsomes and the Km values determined by Lineweaver-Burk treatment. The substituent in the aryl group of the triazene does not significantly effect the magnitude of Km, which is of the same order of magnitude as the Km for aminopyrine. On the other hand, dimethyltriazenes appear to have lower Km values for demethylation than the structurally similar dimethylnitrosamines. Monomethyltriazenes, the proposed active metabolites of the dimethyltriazenes, do not undergo appreciable demethylation in the presence of microsomes and it appears that the dimethyltriazenes only demethylate once during metabolism. Spontaneous formaldehyde release from the hydroxymethyltriazene in the presence of the Nash reagent prevented an analogous study of the metabolism of these compounds.

Animals↗
PubMed1981

Triazene metabolism. II. Transportability and enzyme inhibitory characteristics of metabolites of antitumor dimethyltriazenes.

A series of dimethyltriazenes (Ar . N==N . NMe2), monomethyltriazenes (Ar . N==N . NH . Me), and triazene carbinolamines (Ar . N==N . NMe . CH2OH) have been studied for their inhibitory effects on the enzyme, hog liver esterase (EC 3.1.1.1). p-Nitrophenyl acetate was used as the model substrate and the rate of hydrolysis was followed spectrophotometrically at 400 nm, the absorption maximum of the p-nitrophenylate ion. Only triazenes with an ester group in the aryl moiety exhibited significant inhibition. Preincubation of the enzyme with the monomethyltriazene (McO2C . C6H4 . N==N . NHMe) or the methyloltriazene (MeO2C . C6H4 . N==NMe . CH2OH) gave enhanced inhibition, which was not observed when the dimethyltriazene (MeO2C . C6H4 . N==N . NMe2) was preincubated with the enzyme. Inhibition of enzyme activity by the monomethyltriazene was shown to be essentially irreversible, whereas the model substrates, methyl benzoate and methyl p-aminobenzoate, gave reversible inhibition in the same assay. The inhibition by the N-methyloltriazene was only partially reversible. . The results are discussed with relevance to the role of the monomethyltriazenes and N-methyloltriazenes as possible transportable metabolites of the antitumour dimethyltriazenes.

Animals↗