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The Effect of Methanethiol and Methionine Toxicity on the Activities of Cytochrome c Oxidase and Enzymes Involved in Protection from Peroxidative Damage^1,2,

Ann Finkelstein^* and Norlin J. Benevenga^3,*,,

^* Departments of Nutritional Sciences Meat & Animal Science, University of Wisconsin, Madison, WI 53706

The tissue changes characteristic of methionine toxicity may be caused by methanethiol (CH₃SH) inhibition of enzymes involved in protection from peroxidative damage. Methanethiol is an intermediate of the transaminative pathway of methionine metabolism. Glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase activities were therefore tested for susceptibility of CH₃SH. Cytochrome c oxidase activity was also measured because of its known inhibition by mercaptans. A 10-min exposure to CH₃SH depressed hepatic cytochrome c oxidase activity to 28% of the incubated control value, while hepatic, splenic and erythrocyte catalase activities were depressed, respectively, to 53, 52 and 71% of the incubated control. Similar reductions in catalase and cytochrome c oxidase activities were observed in rats fed a diet containing 3% L-methionine as compared to rats pair-fed a control diet containing 0.3% methionine. There was no difference in the amount of lipid peroxidation as monitored by the presence of malondialdehyde in the livers of these rats. In rats injected i.p. with 50 or 75 µmol of 3-methylthiopropionate, an intermediate of methionine catabolism, the maximum levels of exhaled methanethiol coincided with depressions in liver catalase and cytochrome c oxidase activity to 40-50% of control values. The activities of these enzymes returned to control values within 2 to 4 h. The inhibition of catalase activity does not appear to be the cause of the membrane damage observed in methionine toxicity.

KEY WORDS: • rat • methionine • methanethiol • peroxidative damage • cytochrome c oxidase • catalase • glutathione peroxidase • glutathione reductase • superoxide dismutase

¹ This work was supported by Grant AM 15227 from the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases of the National Institutes of Health and by funds from the College of Agricultural and Life Sciences, University of Wisconsin, Madison. This is paper no. 851 from the Department of Meat & Animal Science.

² A preliminary report of this work has appeared. Finkelstein, A. & Benevenga, N. J. (1982) Developmental changes in metabolism via the transaminative pathway of methionine. Fed. Proc. 41, 350 (abs.).

³ Reprint requests should be sent to: N. J. Benevenga, University of Wisconsin, 1156 Animal Sciences Building, 1675 Observatory Drive, Madison, WI 53706.

Manuscript received 24 September 1984. Revision accepted 21 October 1985.

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