Arginase specificity

Arginase specifically hydrolyses natural or (-f)-arginine into the diamino acid ornithine and urea, and is part of the mechanism whereby urea is produced in the animal body. 

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. 

Although mammalian liver arginases can be activated by Co2+, Ni2+, Fe2+, and Cd2+, only Mn2+ is considered [114] to be the physiological activator. Mn2+ is specifically required to activate the arginases from Neurospora crassa [115], Rhodobacter capsulatus [116], and the Agrobacterium TiC58 plasmid. This selectivity is attributed to the unique ability of Mn to orient the bridging water molecule properly for catalysis [81,117],... 

The specific requirement of plants for manganese is also based on the fact that this element is a component of the enzymes arginase and phosphotransferase. However,... 

Noonan, N. E., and D. J. Meyer. 1979. Use of plasma arginase and gamma-glutamyl transpeptidase as specific indicators of hepatocellular or hepatobiliary disease in the dog. American Journal of Veterinary Research 40 942-947. 

Ornithine is an amino acid. However, it is not incorporated into proteins during the process of protein synthesis because no genetic codon exists for this amino acid. Although ornithine is normally regenerated by the urea cycle (one of the products of the arginase reaction), ornithine also can be synthesized de novo if needed. The reaction is an unusual transamination reaction catalyzed by ornithine aminotransferase under specific conditions in the intestine (Fig. 38.14). The usual direction of this reaction is the formation of glutamate semialdehyde, which is the first step of the degradation pathway for ornithine. 

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. 

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