ABSTRACT
Enzyme activity is found at highest levels in mammalian liver [1], where this reaction constitutes the final step of the urea cycle. The flux of sub strate through this step is considerable, since the average adult excretes about 10 kg of urea per year. In addition to its presence in liver, arginase activity has been detected in a number of extrahepatic tissues that lack a complete urea cycle, such as lactating mammary gland [2,3], kidney [4-7], prostate [6], and activated macrophages [5]. In most of these tis sues, the arginase present represents a second isozyme (arginase II) that is distinct in immunological properties, amino acid sequence, and subcellular location from the more abundant liver isozyme (arginase I). The biological function of arginase II has been the subject of consider able interest; current thinking is that this isozyme provides a supply of L-ornithine for proline and polyamine biosynthesis, and along with arginase I it also serves to regulate the levels of L-arginine available for nitric oxide production. The comparative properties of the two arginase isozymes are discussed in a number of recent reviews [8-10]. Arginase I is the more abundant isozyme of the two, and it has been extensively characterized in terms of its biochemistry, enzymology, and three-di mensional structure. Arginase I is a 105-kDa homotrimer, and each 35kDa protomer contains a binuclear manganese cluster required for cat alytic activity. The remainder of this chapter outlines the catalytic mechanism and structure-function relationships for this well-studied isozyme.
