Glutamine-dependent urea synthesis in elasmobranch fishes.

Marine elasmobranchs (sharks, skates, and rays) synthesize and retain in their tissues high concentrations of urea (up to 0.4 M) and certain amines, such as trimethylamine oxide (up to 0.2 M), for the purpose of osmoregulation. Although the pathway of urea synthesis in ureosmotic elasmobranchs is similar to the classical urea cycle in ureotelic species, there are several properties that are unique. Indeed, this might be anticipated, since the primary function of urea synthesis in elasmobranchs is osmoregulation, rather than ammonia detoxification. The existence in different species of a major biosynthetic pathway resulting in the same end product, but which serves quite different physiological purposes in each species, can provide an opportunity for comparative investigations that contribute to our understanding of the regulatory properties and evolutionary development of the pathway. The purpose of this commentary is to consider the unique properties of urea synthesis in elasmobranchs and to comment on the comparative relationships to teleost fishes and mammalian species; most studies discussed here have been carried out with spiny dogfish shark, Squalus acanthias, a representative elasmobranch. Like ureotelic species, hepatic urea synthesis in ureosmotic elasmobranchs requires both mitochondrial and cytosolic enzymes, but there are notable differences (Fig. 1). The most significant difference is that the initial step of ammonia assimilation for urea synthesis in hepatic mitochondria of elasmobranchs is the formation of glutamine, which is subsequently utilized as the substrate for carbamoyl-phosphate synthesis (Anderson and Casey, J. Biol. Chem., 259, 456-462, 1984). This is due to the presence of high levels of glutamine synthetase (GSase) and a unique acetylglutamateand glutamine-dependent carbamoyl-phosphate synthetase (CPSase 111), both localized exclusively in the mitochondrial matrix (Casey and Anderson, J. Biol. Chem., 257,8449-8453, 1982, and Comp. Biochem. Physiol., 82B, 307-315,1985). GSase is a cytosolic enzyme in liver of mammalian species and in some, but not all, teleost fishes. In mammalian and amphibian species the first step of ammonia assimilation for urea synthesis in liver is direct conversion of ammonia to carbamoyl phosphate catalyzed by a corresponding mitochondrial acetylglutamateand ammoniadependent CPSase I (which cannot utilize glutamine as a substrate). The properties of elasmobranch mitochondrial CPSase I11 are similar to the mammalian mitochondrial CPSase I, except for the fact that glutamine rather than ammonia serves as the nitrogen-donating substrate (Anderson, J. Biol. Chem., 256, 12 228 12 238, 1981).