Hepatic arginase

Argininosuccinate lyase (AL) (Fig. 40-5 reaction 4) cleaves argininosuccinate to form fumarate, which is oxidized in the tricarboxylic acid cycle, and arginine, which is hydrolyzed to urea and ornithine via hepatic arginase. Both AL and arginase are induced by starvation, dibutyryl cyclic-AMP and corticosteroids. 

Changes with age in the inducibility of arginase in vivo Increase of Hepatic Arginase ... 

Brock, A-, Chapman, S., Ulman, E and Wu, C. (1994). Dietary manganese deficiency decreases rat hepatic arginase activity /. Nirfr 124, 340-344. 

In mammals, hepatic arginase is the terminal enzyme of the urea cycle, which represents the major end-product of nitrogen metabolism — the average adult human excretes some 10 kg of urea per year. The enzyme is not restricted to the liver, since ornithine is a precursor of the nonessential amino acid proUne, and a biosynthetic precursor of polyamines, required for rapidly dividing tissues. Arginine is also the precursor of the important messenger in many vertebrate signal-transduction pathways nitric oxide, NO (Scheme 16.1), of which more shortly. 

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. 

Symptoms for the first four deficiencies include anorexia, vomiting and lethargy, from which patients may progress to irreversible coma (acute hepatic coma) and death. If infants survive, but remain undiagnosed and untreated for some time, they become mentally handicapped. In arginase... 

Cornelius, C. E., G. M. Douglas, R. R. Gronwall, and R. A. Freedland. 1963. Comparative studies on plasma arginase and transaminases in hepatic necrosis. Cornell Veterinarian 53 181-191. 

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. 

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... 

Elevated levels of certain hepatic enzymes [e.g., aspartate aminotransferase (AST), lactate dehydrogenase (LDH), sorbitol dehydrogenase (SDH), arxl arginase] indicate hepatic necrosis [see Chapter 8 III C 2 a (4) (b). Table 8-1)]. Serum or plasma liver enzymes may be elet ed 3-6 weeks before a hemolytic crisis and may be used to prerict animals at risk. 

Arginase occurs in the livers of all animals that are ureotelic in that they excrete their waste nitregen chiefly in the form of urea. It is absent from the livers of uricotelic animals (birds and most reptiles), which excrete nitrogen as uric acid. Traces of the enzyme may occur in non-hepatic tissue, and it has also been identified in plants. 

Location of Ureagenesis.— It has been suggested that ureagenesis is a property of most tissues, but perfusion and incubation experiments have shown that the mechanism is narrowly restricted to the liver, and there is no evidence that urea can be assembled from ammonia and carbon dioxide in any other tissue in the mammal, although the presence of arginase in the kidney may account for a slight subsidiary extra-hepatic production of urea from surplus arginine. 

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