An active urea cycle and carbamoyl-phospahte synthetase ffl in muscle of an alkaline lake-adapted fish

Most fish are ammonotelic, but under certain circumstances some fish excrete urea as a major excretory product and have an active urea cycle. An example is the alkaline lake-adapted tilapia (Orcochromis alcalicus grahami) that lives in waters at pH 10 and excretes nitrogen wastes as urea instead of ammonia. The units in liver of the glutaminc- and acetylglutamate-dependent carbamoyl-phosphate synthetase lu (CPSase HI), which catalyzes the first step of the urea cycle in fish, are not sufficient to account for the levels of urea excreted. However, high levels of CPSase III and all the other urea cycle enzymes are present in muscle tissue; the units per g tissue are much higher than in liver and are sufficient to account for the urea excreted. The CPSase III has kinetic properties that appear to be different from those reported for CPSase HI in Squalus acanthias or Micropterus sabnoides: the Vmax with ammonia as nitrogen-donating substrate is nearly as high as that with glutamine; acetylglutamate has little effect on Km for glutamine and vice versa, but does significantly decrease the Km for ATP and change the kinetics from sigmoid to hyperbolic. The sequence of the cDNA for the CPSase in has been determined. Low levels of CPSase HI and ornithine carbamoyltransferase in muscle of several teleostean fishes have been reported recently; the results here suggest that the presence of the urea cycle in extrahepatic tissues of teleostean fishes may be physiologically significant.