Arginase, function

We begin this overview of manganese biochemistry with a brief account of its role in the detoxification of free radicals, before considering the function of a dinuclear Mn(II) active site in the important eukaryotic urea cycle enzyme arginase. We then pass in review a few microbial Mn-containing enzymes involved in intermediary metabolism, and conclude with the very exciting recent results on the structure and function of the catalytic manganese cluster involved in the photosynthetic oxidation of water. 

Arginase (EC 3.5.3.T) mediates the hydrolytic cleavage of L-canavanine to produce L-canaline and urea. L-Canaline, 2-amino-4-aminooxybutyric acid, bears the same structural analogy to L-ornithine as canavanine does to arginine. The aminooxy group of canaline with its pK value of 3.96 differs markedly from the 6-amino function of ornithine (pK = 10.76). 

The complete urea cycle as it occurs in the mammalian liver requires five enzymes Argininosuccinate synthase, arginase, and argininosuccinate lyase (which function in the cytosol), and ornithine transcarbamoylase, and carbamoyl phosphate synthase (which function in the mitochondria). Additional specific transport proteins are required for the mitochondrial uptake of L-ornithine, NH3, and HC03 and for the release of L-citrulline. 

Kuhn NJ, Ward S, Piponski M, et al. 1995. Purification of human hepatic arginase and its manganese (Il)-dependent and pH-dependent interconversion between active and inactive forms A possible pH sensing function of the enzyme on the ornithine cycle. Arch Biochem Biophys 320 24-34. 

The catabolism of amino acids results in the release of nitrogen. Many parasites excrete the excess nitrogen in the form of ammonia. In protozoa there is no evidence for a complete urea cycle which would allow the conversion of ammonia into urea, and urea released by some species (49,50) is likely to be formed solely as a product of arginine catabolism. Urea makes up between 2 and 10% of the total nitrogenous end-product of helminths, but evidence for a functional urea cycle in parasitic species has been equivocal (1). Arginase and ornithine carbamoyltransferase do occur widely but the other urea cycle enzymes do not. Small quantities of uric acid are excreted by some cestodes and trematodes. 

Two other types of regulation control the urea cycle allosteric activation of CPSI by 7V-acetylglutamate (NAG) and induction/repression of the synthesis of urea cycle enzymes. NAG is formed specifically to activate CPSI it has no other known function in mammals. The synthesis of NAG from acetyl CoA and glutamate is stimulated by arginine (Fig. 38.15). Thus, as arginine levels increase within the liver, two important reactions are stimulated. The first is the synthesis of NAG, which will increase the rate at which carbamoyl phosphate is produced. The second is to produce more ornithine (via the arginase reaction), such that the cycle can operate more rapidly. 

---