Arginase:
 structure, mechanism, and physiological role in male and female sexual arousal.

 D.W. Christianson, Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street,
 Philadelphia, PA 19104-6323, USA, Acc Chem Res. 2005 Mar;38(3):191-201. Mammalian arginases I and II require an intact binuclear
 manganese cluster for the hydrolysis of L-arginine to generate L-ornithine and urea. Although arginase isozymes differ in terms of their tissue
 distribution, cellular localization, and metabolic function, each employs a metal-activated hydroxide mechanism for catalysis. To date, the
 best arginase inhibitors are those bearing N-hydroxyguanidinium or boronic acid "warheads" that can bridge the binuclear manganese
 cluster. Strikingly, the trigonal planar boronic acids undergo nucleophilic attack by hydroxide ion to form tetrahedral boronate anions that
 mimic the tetrahedral intermediate and its flanking transition states in the arginase mechanism. Given their affinity and specificity for arginase,
 boronic acid inhibitors are especially useful for probing the role of arginase in living systems. Arginase can regulate L-arginine bioavailability
 to nitric oxide synthase by depleting the substrate pool for NO biosynthesis, so arginase inhibition can enhance the substrate pool for NO
 biosynthesis. Accordingly, arginase inhibition  can enhance NO-dependent physiological processes, such as the smooth muscle relaxation
 required for sexual arousal: administration of arginase inhibitors in vitro and in vivo enhances erectile function and engorgement in the male
 and female genitalia. Therefore, arginase is a potential therapeutic target for the treatment of sexual arousal disorders in men and women.

 PMID: 15766238 [PubMed - indexed for MEDLINE