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Response of Oxidative Phosphorylation in Rat Liver to Prolonged Protein Depletion

Laboratory of Nutrition and Endocrinology, National Institutes of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland 20014

The effects of prolonged protein depletion followed by repletion upon succinate oxidation in a phosphorylating system in rat liver were studied. Adult male albino rats were depleted of protein for 102 days using two proteinfree diets, one containing 0.3% L-methionine and the other no methionine. Ad libitum-fed controls received the same basal diet plus 20% casein and 0.3% L-methionine. Another control group was pair-fed the complete diet with the group receiving neither casein nor methionine. After 24, 56, and 102 days, liver homogenates were assayed for succinic oxidase in a phosphorylating system. Phosphorylation associated with succinate oxidation was simultaneously measured. In the protein- and methionine-free group succinic oxidase decreased to 65% of the control value (P < 0.01) after 102 days but increased to 165% (P < 0.01) in the group receiving methionine but no protein. Phosphate uptake decreased to 65% (P < 0.01) and increased to 125% (P < 0.01) in the two groups, respectively. The P/O ratios did not change significantly in the proteinand methionine-free group but decreased to 78% (P < 0.01) of the controls in the group receiving methionine without protein. These results indicate that the system is uncoupled significantly in the group fed the protein-free diet containing 0.3% L-methionine. When protein was returned to the diets of the two protein-deficient groups, succinate oxidation gradually returned to normal after 88 days of repletion. Phosphorylation in both experimental groups rebounded to higher than normal levels after 2 days of repletion but then slowly returned to normal after 88 days of repletion. Additional studies, in which each essential amino acid as well as cystine, glutamic acid, and arginine were included individually at levels equimolar with 0.3% methionine in the protein-free ration and fed for 42 days, indicated that methionine and cystine have equivalent effects on the enzyme activities and the P/O ratios. The other amino acids tested had no effect on the enzyme systems.