Response of the Liver to Prolonged Protein Depletion

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Abstract
A timed study of changes in the succinic oxidase system and its component enzymes during a prolonged deficiency of dietary protein followed by repletion has been presented. Pair-fed and ad libitum-fed controls were included throughout. The data were calculated as activity or concentration per milligram of fresh liver, per milligram of liver nitrogen, and per milligram of liver deoxyribonucleic acid (DNA). The results are summarized as follows: Based on fresh liver, the succinic oxidase activity (SO) of the protein-deficient rats dropped after 10 days to 50% of normal followed by an increase to above normal after 30 days. This activity in the pair-fed controls increased throughout the depletion period. The SO of both groups rapidly returned to normal after repletion. The succinic dehydrogenase (SD) of the protein-deficient group followed the same pattern as SO for that group. The SD of the pair-fed controls increased until 46 days and then decreased at 72 days. Both groups tended to return to normal following repletion; however, the SD of the protein-deficient group was significantly higher than that of the pair-fed controls even after 48 days of repletion. The antimycin A-sensitive activity (AAS) of both the protein-deficient and the pair-fed groups increased gradually and at the same rate throughout the depletion period. Following repletion, the AAS of neither group returned to normal at once; after 48 days of repletion, however, it returned to normal in both groups. Cytochrome c of both the protein-deficient and pair-fed groups increased above normal to the same extent and leveled off after 30 days of depletion. After repletion the cytochrome c of both groups gradually returned to normal. Cytochrome oxidase (CO) of the protein-deficient animals fell rapidly to 25% of normal. The CO of the pair-fed controls did not change throughout the study. Following repletion, the CO of the protein-deficient rats returned rapidly to normal. Based on liver nitrogen, the SO of the protein-deficient and pair-fed groups followed about the same pattern as for SO per milligram of fresh liver. The SD of the protein-deficient group followed the same pattern as the SD per milligram of fresh liver for that group; the initial loss of activity of SD per milligram of nitrogen was not as great as SD per milligram of liver. The SD for the pair-fed controls increased until 46 days and then fell to normal by 72 days. Following repletion, the SD of both groups returned slowly to normal. The AAS of the protein-deficient group increased rapidly to well above normal by 30 days and leveled off. Following repletion a sharp further increase occurred with a return to normal after 48 days of repletion. The AAS of the pair-fed controls did not change throughout the study. Cytochrome c of the protein-deficient group reached 190% of normal after 10 days of depletion and remained at that level until repletion was begun. The cytochrome c of pair-fed controls increased to 130% of normal and remained there during depletion. Following repletion the cytochrome c of both groups slowly returned to normal. The CO of the protein-deficient and pairfed groups followed the same patterns as for CO per milligram fresh liver. Based on liver DNA, which is a measure of activity or concentration per liver cell, the SO of the protein-deficient rats dropped to 40% of normal after 10 days, which was followed by an increase for the rest of the depletion period. Following repletion, a decrease occurred after two days followed by a return to normal after 46 more days. The SO of the pair-fed controls remained nearly normal throughout the study. The SD of the protein-deficient group followed the same pattern as SO per milligram DNA for that group except that an immediate return to normal occurred after two days of repletion. The SD of the pair-fed group decreased to 70% of normal after 30 days, returned to normal at 46 days, and then fell to 70% of normal at 72 days. Repletion brought the SD of this group slowly back to normal. The AAS of both the protein-deficient and pair-fed groups fell to 60 to 70% of normal after 10 days and remained there throughout the depletion period. Repletion brought the AAS of both groups immediately back to normal. No change in cytochrome c occurred in either group throughout the study. The CO of the protein-deficient rats fell to 15% of normal by 46 days. It fell to 60% of normal in the pair-fed controls. The CO of both groups rapidly returned to normal following repletion.