Urea cycle enzymes in retina, ciliary body-iris, lens and senile cataracts

Abstract

Carbamylation of lens proteins induces conformational changes and may play a role in the development of cataracts in uremic patients. Thus, the activities of the urea cycle enzymes: carbamyl phosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinase and arginase, were determined in lens, retina and ciliary body-iris of calf and rabbit. No ornithine transcarbamylase activity was found in ciliary body-iris, lens and retina of calf and rabbit whereas carbamyl phosphate synthetase I, argininosuccinate synthetase, argininosuccinase and arginase activities in calf lens were 5·02±0·21, 9·50±0·29, 9·17±0·16 and 6·32±0·19 [μmol (g protein) −1 hr −1], respectively. Except arginase, the activities of carbamyl phosphate synthetase I, argininosuccinate synthetase and argininosuccinase in lens were 30–50% of the values in retina or ciliary body-iris. The K m for each of the substrates was obtained for argininosuccinate synthetase, argininosuccinase and arginase of calf lens. Activities of carbamyl phosphate synthetase I, argininosuccinate synthetase, argininosuccinase and arginase in clear human lenses, aged 67–87 years, were 0·11±0·01, 0·67±0·01, 0·20±0·01 and 0·58±0·03 (μmol lens −1 hr −1), respectively. Two-fold increase in the activity of arginase was found in senile cataracts, but all other enzymes had 36–87% decreases in activities. It is likely that the rise in arginase activity in cataracts could facilitate polyamine synthesis through ornithine and ornithine decarboxylase and additional formation of cyanate, a carbamylating compound, both of which have been implicated in cataract formation. Further, decreased activities of argininosuccinate synthetase and argininosuccinase together with increased arginase activity could lead to the depletion of arginine in senile cataracts.