Metabolism of urea cycle intermediates in chronic renal failure

Abstract

In the chronically uremic rat, elevated citrulline levels in plasma and various tissues were associated with a decreased activity of renal arginine synthetase. The change in activity of this enzyme appeared to have some specificity since renal arginase and transamidinase activities were not diminished. Alterations in the metabolism of two urea cycle intermediates, arginine and onithine were also observed in the uremic rat. Although uremic rats fed arginine-free diets showed no reduction in growth rate as compared to uremic rats ingesting arginine, their plasma arginine levels were decreased, 14C arginine incorporation into proteins of muscle and kidney was less and the muscle polysome profile was altered. All three catabolic pathways of ornithine appeared to be impaired in uremic rats as shown by decreased activities of ornithine transcarbamoylase, transaminase, and decarboxylase when these enzymes were measured in vitro. Additionally, in vivo measurements indicated a reduction in ornithine decarboxylation. These data obtained in the chronically uremic rat suggest that since patients with renal failure have elevated plasma levels of citrulline, arginine and ornithine metabolism may also be altered. Putrescine, the decarboxylation product of ornithine, participates in the formation of polyamines, compounds that regulate DNA and RNA metabolism and thus affect protein synthesis. Hence, it is possible that polyamine formation may be impaired in uremia and this may contribute to muscle protein loss and the wasting condition commonly seen in renal failure.