Liver proline oxidase activity and collagen synthesis in rats with cirrhosis induced by carbon tetrachloride

In rats treated with CCl₄ for 7 weeks, liver proline oxidase activity was drastically reduced 24 h after the initial administration of the toxic agent and remained low throughout the treatment period. This was accompanied by a larger accumulation of added proline in the incubation medium and a lesser release of ¹⁴CO₂ from ¹⁴C]proline during incubation.Collagen synthesis by liver slices of CCl₄-treated rats increased in proportion to proline concentration, a plateau being reached at 0.48 mM proline. The plateau did not occur within the range studied with liver slices of normal liver.Increased collagen synthesis in vitro was accompanied by increased deposition of collagen in vivo only during the first 3 weeks of CCl₄ treatment. No further increase in liver collagen content occurred thereafter. Discontinuance of CCl₄-administration was followed by a return to normal of proline oxidase activity and in vitro collagen synthesis within 2 weeks. Nevertheless, collagen content remained elevated.The results suggest that proline oxidase activity, together with the previously shown increased formation of proline from precursor amino acids, may control the amount of proline available for collagen biosynthesis; and that the rate of degradation of collagen, perhaps by collagenase, may determine the levels of collagen remaining after discontinuance of CCl₄-administration.