N-ACETYL-L-GLUTAMATE AND THE UREA CYCLE IN GULF TOADFISH (OPSANUS-BETA) AND OTHER FISH

Carbamoyl phosphate synthetase I (CPSase I) catalyzes the first reacti on of the urea cycle in mammalian ureotelic species, The positive allo steric cofactor N-acetyl-L-glutamate (AGA) is required for CPSase I ac tivity and is important for regulation of the urea cycle, A similar en zyme, CPSase III, catalyzes this reaction in fish; CPSase III differs from CPSase I in that it utilizes glutamine as the nitrogen-donating s ubstrate instead of ammonia, AGA also stimulates the CPSase III-cataly zed reaction, but is not absolutely required for activity if the gluta mine concentration is high, There has been no report of the presence o r function of AGA in fish, Here we report that AGA is present in those species and tissues of fish that have significant levels of CPSase II I and urea cycle activity; the levels of AGA were higher in liver of a dult gulf toadfish (Opsanus beta) and spiny dogfish shark (Squalus aca nthias), both of which have high CPSase III activity, than in bass (Mi cropterus salmoides) or trout (Oncorhynchus mykiss), which have much l ower or no CPSase III activity, respectively, In the toadfish the leve ls of AGA in liver and muscle tissue were considerably higher in the f ed than in the fasting state, as is observed in mammalian species; in liver, but not in muscle, the level of AGA increased when the toadfish were confined (stressed), which has been shown to induce a ureotelic response, Toadfish muscle had CPSase III and ornithine carbamoyltransf erase activities; the increase in AGA concentration in muscle when fed suggests that the presence of these first two enzymes of the urea cyc le in muscle may be physiologically significant. The results indicate that the fish investigated have physiologically significant levels of AGA and that the levels correlate with parameters related to urea cycl e activity. (C) 1998 Academic Press.