Arginase is a primordial enzyme, widely distributed in the biosphere and represented in all primary kingdoms. It plays a critical role in the hepatic metabolism of most higher organisms as a cardinal component of the urea cycle. Additionally, it occurs in numerous organisms and tissues where there is no functioning urea cycle. Many extrahepatic tissues have been shown to contain a second form of arginase, closely related to the hepatic enzyme but encoded by a distinct gene or genes and involved in a host of physiological roles. A variety of functions has been proposed for the “extrahepatic” arginases over the last three decades. In recent years, interest in arginase has been stimulated by a demonstrated involvement in the metabolism of the ubiquitous and multifaceted molecule nitric oxide. Molecular biology has begun to furnish new clues to the disparate functions of arginases in different environments and organisms. Comparative studies of arginase sequences are also beginning to elucidate the comparative evolution of arginases, their molecular structures and the nature of their catalytic mechanism. Further studies have sought to clarify the involvement of arginase in human disease. This review presents an outline of the current state of arginase research by giving a comparative overview of arginases and their associated properties.

Comparative properties of arginases.

10 – the biology of metamorphosis

The basic pathways of intermediary metabolism that have been investigated so far in salmonid fish are very similar to those occurring in mammals and other animals, though important differences do exist with regards to the presence/absence and physiological importance of some pathways. Salmonids like many other fish, have relatively high dietary requirements for both protein and essential amino acids which in some cases are more than twice those of rat, chicken and pig (see reviews by Mertz, 1972; Cowey, 1975, 1979; Ogino, 1980). Carbohydrates are relatively poorly utilised by fish and the evidence suggests that proteins together with lipids are the major sources of energy (Atherton & Aitken, 1970; Pieper & Pfeffer, 1978; Cr6ach & Serfaty, 1974; Mommsen et al., 1980). This contrasts to the situation in omnivorous mammals where, under normal nutritional conditions, protein catabolism is of little significance in supplying energy whereas carbohydrates and lipids are important energy sources. Phillips (1969) has suggested that 70% of dietary calories in trout feed is from protein, thus a greater percentage of dietary protein is metabolised for energy, rather than utilized for body protein synthesis. Since the end produce of N-metabolism in teleosts is ammonia rather than the more energy costly urea or uric acid (as in mammals, birds and reptiles), fish do not derive the same amounts of energy from dietary constituents as do mammals and hence food protein may have a higher metabolisable energy than carbohydrates. The energy requirements of fish (being poikilothermic) are lower than mammals which expend much energy to maintain their body temperature. Since fish body temperature varies with the water temperature, then reaction rates and occurrence of some pathways within the fish are affected by the environmental temperature. This article is a somewhat brief attempt to describe aspects of the intermediary metabolism of amino acids, carbohydrates and lipids that have been reported for salmonids (predominantly).

Aspects of intermediary metabolism in salmonid fish

Elasmobranch fishes, the coelacanth, estivating lungfish, amphibians, and mammals synthesize urea by the ornithine-urea cycle; by comparison, urea synthetic activity is generally insignificant in teleostean fishes. It is reported here that isolated liver cells of two teleost toadfishes, Opsanus beta and Opsansus tau, synthesize urea by the ornithine-urea cycle at substantial rates. Because toadfish excrete ammonia, do not use urea as an osmolyte, and have substantial levels of urease in their digestive systems, urea may serve as a transient nitrogen store, forming the basis of a nitrogen conservation shuttle system between liver and gut as in ruminants and hibernators. Toadfish synthesize urea using enzymes and subcellular distributions similar to those of elasmobranchs: glutamine-dependent carbamoyl phosphate synthethase (CPS III) and mitochondrial arginase. In contrast, mammals have CPS I (ammonia-dependent) and cytosolic arginase. Data on CPS and arginases in other fishes, including lungfishes and the coelacanth, support the hypothesis that the ornithine-urea cycle, a monophyletic trait in the vertebrates, underwent two key changes before the evolution of the extant lungfishes: a switch from CPS III to CPS I and replacement of mitochondrial arginase by a cytosolic equivalent.

Evolution of urea synthesis in vertebrates: the piscine connection

Ammonia is toxic to all vertebrates. It can be converted to the less toxic urea, but this is a metabolically expensive process found only in terrestrial vertebrates that cannot readily excrete ammonia and marine fish that use urea as an osmotic filler. Freshwater fish mostly excrete ammonia with only a small quantity of urea. It seems the ornithine cycle for urea production has been suppressed in all freshwater teleosts except for some airbreathers which, when exposed to air, increase urea synthesis via the cycle. Here we show that the tilapia fish Oreochromis alcalicus grahami, the only fish living in Lake Magadi, an alkaline soda lake (pH = 9.6-10) in the Kenyan Rift Valley, excretes exclusively urea and has ornithine-urea cycle enzymes in its liver. A closely related species that lives in water at pH 7.1 lacks these enzymes and excretes mainly ammonia with small amounts of urea produced via uricolysis. It dies within 60 min when placed in water from Lake Magadi. We suggest that urea production via the ornithine-urea cycle permits O. a. grahami to survive the very alkaline conditions in Lake Magadi.

E. Baldwin

Papers

Ornithine-urea cycle enzymes in teleostean fish

The adaptation of amphibian waste nitrogen excretion to dehydration.

A comparative study of nitrogen excretion in some Amphibia and reptiles.

The comparative biochemistry of carbamoyl phosphate-L-ornithine carbamoyltransferases in relation to their evolution

The synthesis of acetyl phosphate by homogenates of elasmobranch liver.