Rat liver arginase

Figure 16.4 Dinuclear Mn centre of rat liver arginase. (From Ash, 2004. Copyright 2004, the American Society for Nutritional Science.)...

The 2.8 A resolution crystal structure of the arginase from the thermophilic bacterium Bacillus caldevelox [112] reveals a hexameric structure with at least one Mn2+ bound per subunit. The 2.1 A resolution structure of rat liver arginase, reported recently [81], reveals it to be trimeric, with the overall fold of the arginase monomer belonging to the a/p protein class. The Mn"Mnn aggregate, shown in Figure 24, is found at the bottom of a 15 A active-site cleft. 

C6. Cittadini, D., Pietropaolo, C., de Cristoforo, D., and d Ayello-Caracciolo, M., In vivo effect of L-lysine on rat liver arginase. Nature (London) 203, 643-644 (1964). 

Fig. 1. Structure of the active site of the rat liver arginase enzyme based on (S).

The reactivity of catalase enzymes and rat liver arginase may also now be directly compared. Arginase has recently been reported to dis-... 

Figure 11 Schematic drawing of the active site of native rat liver arginase.

Maggini, S., Stoecklintschan, F.B., Morikoferzwez, S. Walter, P. (1992). New kinetic-parameters for rat-liver arginase measured at near-physiological steady-state concentrations of arginine and Mn. Biochem.., 283, 653-60. 

N -Hydroxy-nor-L-arginine is a potent competitive inhibitor of rat liver arginase (Custot et al. 1997) but neither a substrate nor an inhibitor of purified recombinant iNOS (Moali et al. 1998). 

Carl GF, Blackwell LK, Barnett EC, et al. 1993. Manganese and epilepsy Brain glutamine synthetase and liver arginase activities in genetically epilepsy prone and chronically seizured rats. Epilepsia 34 441-446. 

Low et al. (2004) have proposed a model to explain thioacetamide-induced hepatotox-icity and cirrhosis in rat livers. The pathways of thioacetamide-induced liver fibrosis were found to be initiated by thioacetamide S-oxide derived from the biotransformation of thioacetamide by the microsomal flavin-adenine nucleotide containing monooxygenase and cytochrome P450 systems and involve oxidative stress and depletion of succinyl-CoA, thus affecting heme and iron metabolism. Karabay et al. (2005) observed such hepatic damage in rats with elevation of total nitrite level in livers and decrease in arginase activity. The authors have reported that nitrosative stress was essentially the critical factor in thioacetamide-induced hepatic failure in rats. 

Schimke, R. T., 1964, The importance of both synthesis and degradation in control of arginase levels in rat liver, J. Biol. Chem. 239 3808. 

Ikemoto, M., S. Tsunekawa, Y. Toda, and M. Totani. 2001. Liver-type arginase is a highly sensitive marker for hepatocellular damage in rats. Clinical Chemistry 47 946-948. 

These enzymes catalyze the hydrolysis of L-arginine to form L-ornithine and urea. Mammalian arginases have been divided into classes I and II as a function of their location arginase I is predominantly found in the liver whereas arginase II is located in non-hepatic tissues and functions primarily in L-arginine homeostasis [110]. The crystal structure of rat arginase I has shown the active site to be composed of a Mn binuclear center. The Mn(II) and Mn(II)g ions which are... 

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