Regulation of arginine and ornithine metabolism at the enzymic level in rat liver and kidney

Abstract

The effects on the activities of the enzymes which metabolize ornithine and arginine in liver and kidney have been studied by feeding rats diets containing 8% ornithine, arginine, or proline and 10 or 20% casein. In liver the enzymes studied were arginase, ornithine transcarbamylase, argininosuccinic acid lyase, and ornithine-δ-transaminase. The ratios of their activities were 3000:414::10:1, respectively. In kidney the enzymes studied were arginase, ornithine-δ-transaminase, and arginine-glycine transamidinase. The ratios of their activities were 24:2::7:1.0. Several of these enzymes were inducible to higher activities by feeding diets with the added amino acids. Of these, the most sensitive to substrate induction was liver ornithine-δ-transaminase. This enzyme, which had the lowest specific activity of those studied, showed an increase in specific activity of 250.6% when ornithine was added to the 20% casein diet. Arginine and proline were somewhat less effective as inducers. This difference in inducing ability was further accentuated by the 10% casein diet. This indicated that ornithine is probably the primary inducer of liver ornithine-δ-transaminase, and that arginine and proline probably act by conversion to ornithine. Kidney ornithine-δ-transaminase was also inducible, but to a lesser extent (28.7%) and only by ornithine added to the 20% casein diet. Liver ornithine transcarbamylase was induced maximally by ornithine on the 20% casein diet. The induction of this enzyme was relatively much less (31.2%) than that of liver ornithine-δ-transaminase, but in absolute amounts its change in activity was 50 times greater than the change in liver ornithine-δ-transaminase. On the 10% protein diet, arginine produced an inhibition of growth and a decrease in liver weight. This was accompanied by a 37.7% depression in the activity of liver arginase and a 23.5% depression in the activity of liver ornithine transcarbamylase, changes which probably reflect a general inhibition of protein synthesis.