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Response of the Liver to Prolonged Protein Depletion

IV. Protection of Succinic Oxidase and Succinic Dehydrogenase by Dietary Methionine and Cystine in a Protein-Free Ration

Laboratory of Nutrition and Endocrinology, National Institute of Arthritis and Metabolic Diseases, U. S. Department of Health, Education and Welfare, Public Health Service, National Institutes of Health, Bethesda, Maryland

The influence of including 0.3% DL-methionine in a protein-free ration upon liver succinic oxidase, succinic dehydrogenase, and protein was studied in the adult male rat. The changes were followed as a function of time during protein depletion followed by repletion. Enzyme assay systems were used in which the mitochondria were "damaged" by including calcium ions in the media, thus allowing free access of substrates and dye acceptor to the enzymes. The results with succinic oxidase and succinic dehydrogenase were almost identical, clearly indicating that the rate-limiting step in the succinic oxidase system under these conditions is at the initial dehydrogenase. In the group receiving the protein-free ration without methionine, the activities of the enzymes decreased to 40% of normal after 8 weeks with a slight increase toward normal after about 15 weeks. In the group receiving methionine in the protein-free ration, after an initial decrease to 60% of normal after 3 weeks (which was identical to the response in the group receiving no protein and no methionine), a rapid increase toward normal occurred with normal values for these enzymes being reached after 15 weeks. No significant change occurred in the pair-fed controls throughout the study. Protection of liver protein by methionine in a protein-free ration was also observed. Results from further studies with all other essential amino acids as well as cystine, arginine, and glutamic acid, added individually to the protein-free ration at levels equivalent to 0.3% methionine, indicated that cystine as well as methionine significantly protected the liver cells against loss of succinic oxidase and succinic dehydrogenase. No other amino acid tested showed this effect. Both cystine and methionine also protected liver cells from loss of other protein but to a less extent than succinic oxidase and succinic dehydrogenase.