Cysteine conjugate S-oxidase. Characterization of a novel enzymatic activity in rat hepatic and renal microsomes.
Cysteine conjugate S-oxidase activity, with S-benzyl-L-cysteine as substrate, was found mostly in the microsomal fractions of rat liver and kidney. In the presence of oxygen and NADPH, S-benzyl-L-cysteine is converted to S-benzyl-L-cysteine sulfoxide; no S-benzyl-L-cysteine sulfone was detected. The Vmax for S-benzyl-L-cysteine sulfoxide formation by kidney microsomes was nearly 3-fold greater than the rate measured with liver microsomes. Inclusion of catalase, superoxide dismutase, glutathione, butylated hydroxyanisole, the peroxidase inhibitor, potassium cyanide, the cytochrome P-450 inhibitors, 1-benzylimidazole and metyrapone, or a monoclonal antibody to cytochrome P-450 reductase did not inhibit the metabolic reaction. Flavin-containing monooxygenase alternate substrates, N,N-dimethylaniline, n-octylamine, and methimazole inhibited the S-oxidase activities. Analogues of S-benzyl-L-cysteine, S-methyl-L-cysteine, and S-(1,2-dichlorovinyl)-L-cysteine inhibited the S-benzyl-L-cysteine S-oxidase activities, whereas S-carboxymethyl-L-cysteine and S-benzyl-L-cysteine methyl ester had no effect. These results provide clear evidence against the involvement of reactive oxygen intermediates or cytochrome P-450 in the sulfoxidation of S-benzyl-L-cysteine and indicate that the S-oxidase activities may be associated with flavin-containing monooxygenases which exhibit selectivity in the interaction with cysteine S-conjugates.
Sausen
P J
PJ
Department of Comparative Biosciences and Environmental Toxicology Center, University of Wisconsin, Madison 53706.
Elfarra
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology
D000911:Antibodies, Monoclonal; C002206:S-benzylcysteine; D010088:Oxidoreductases; C063574:cysteine conjugate S-oxidase; D003545:Cysteine