Ammonia is the major metabolic end product during the catabolism of proteins, amino acids and other nitrogen containing biomolecules in different animal tissues. Ammonia is very toxic to the fish. Its toxicity leads to reduced growth rate (Atwood et al., 2000; El-Shafai et al., 2004; Hegazi and Hasanein, 2010), disruption of ion-osmo homeostasis (Knoph and Thorud, 1996; Person-Le Ruyet et al., 2003, 1998), gill hyperplasia (Benli et al., 2008), and if present in very high concentration, it causes hyperexcitability, coma, convulsions and finally death (Ip et al., 2001b).
To survive the effect of the ammonia toxicity, fish modifies its metabolism by either decreasing the production of ammonia, increasing its excretion, or converting the ammonia to glutamine and/or urea (Ip et al., 2001b). Most of the freshwater teleosts are ammoniotelic, as they excrete ammonia as primary excretory product to the external environment mainly by diffusion through the gills (Saha and Ratha, 2007). But, several species of fish have adapted to unique environmental circumstances by expressing high levels of OUC-enzymes and thus converting more than 50% of waste nitrogen as urea-N, they are considered as ureotelic (Anderson, 2001; Saha and Ratha, 2007). Though, quite a few recent studies have proposed an alternate to ureotelism (i.e. increased OUC pathway activity) as a mechanism for responding to such environmental circumstances. For example, in marble goby (Oxyeleotris marmoratus) a facultative freshwater air-breather, which can tolerate continuous air exposure for up to a week, glutamine synthetase (GS) appears to function as ammonia trap (Jow et al., 1999). A similar observation was made in the swamp eel (Monopterus albus) (Tay et al., 2003) and in the sleeper (Bostrichthys sinensis) (Ip et al., 2001b). There could be some other ways of handling ammonia toxicity such as partial catabolism of amino acid leading to the accumulation of alanine as in the giant mudskipper (Periophthalmodon schlosseri) (Ip et al., 2001c) and snakehead (Chana asiatica) (Chew et al., 2004), and also conversion of ammonia to some non-essential amino acids in walking catfish (Saha et al., 2002, 2000).
Glutamine synthetase (GS) [L-glutamate:ammonia ligase (ADP forming); E.C. 220.127.116.11] catalyzes the ATP-dependent formation of glutamine from ammonia and glutamate. Eight identical subunits make up the functional enzyme, with very less amount of difference amongst subunits that is may be due to post-translational modifications. (Smirnov et al., 2000). In mammals GS is encoded by a single gene, although some reports of pseudogenes have also been noted (Kuo and Darnell Jr, 1989; Wang et al., 1996). Elasmobranch fishes and birds also display a single GS gene, while they produce different transcripts for mitochondrial and cytosolic isozymes (Campbell and Smith, 1992; Haifeng and Young, 1989; Laud and Campbell, 1994).
In fish, GS is a multifunctional enzyme and its product glutamine has...