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Arginase family This family includes arginase, also known as arginase-like amidino hydrolase family, and related proteins. Arginase is a binuclear Mn-dependent metalloenzyme and catalyzes hydrolysis of L-arginine to L-ornithine and urea (Arg, EC 3.5.3.1), the reaction being the fifth and final step in the urea cycle, providing the path for the disposal of nitrogenous compounds. Arginase controls cellular levels of arginine and ornithine which are involved in protein biosynthesis, and in production of creatine, polyamines, proline and nitric acid. In vertebrates, at least two isozymes have been identified: type I (ARG1) cytoplasmic or hepatic liver-type arginase and type II (ARG2) mitochondrial or non-hepatic arginase. Point mutations in human arginase ARG1 gene lead to hyperargininemia with consequent mental disorders, retarded development and early death. Hyperargininemia is associated with a several-fold increase in the activity of the mitochondrial arginase (ARG2), causing persistent ureagenesis in patients. ARG2 overexpression plays a critical role in the pathophysiology of cholesterol mediated endothelial dysfunction. Thus, arginase is a therapeutic target to treat asthma, erectile dysfunction, atherosclerosis and cancer. |
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