Arginase (EC 3.5.3.1) are manganese-containing isoforms, which appear to show differential distribution, where the ARG1 isoform predominates in the liver and erythrocytes, while ARG2 is associated more with the kidney.

N^ω-hydroxyarginine, an intermediate in NOS metabolism of L-arginine acts as a weak inhibitor and may function as a physiological regulator of arginase activity. Although isoform-selective inhibitors of arginase are not available, examples of inhibitors selective for arginase compared to NOS are N^ω-hydroxy-nor-L-arginine [6], S-(2-boronoethyl)-L-cysteine [3,5] and 2(S)-amino-6-boronohexanoic acid [2-3].

1. Baggio R, Elbaum D, Kanto ZF, Carroll PJ, Cavalli RC, Ash DE, Christianson DW. (1997) Inhibition of Mn2⁺2-Arginase by Borate Leads to the Design of a Transition State Analogue Inhibitor, 2(S)-Amino-6-boronohexanoic Acid. J Am Chem Soc, 119 (34): 8107–8108.

2. Baggio R, Emig FA, Christianson DW, Ash DE, Chakder S, Rattan S. (1999) Biochemical and functional profile of a newly developed potent and isozyme-selective arginase inhibitor. J Pharmacol Exp Ther, 290 (3): 1409-16. [PMID:10454520]

3. Colleluori DM, Ash DE. (2001) Classical and slow-binding inhibitors of human type II arginase. Biochemistry, 40 (31): 9356-62. [PMID:11478904]

4. Ilies M, Di Costanzo L, North ML, Scott JA, Christianson DW. (2010) 2-aminoimidazole amino acids as inhibitors of the binuclear manganese metalloenzyme human arginase I. J Med Chem, 53 (10): 4266-76. [PMID:20441173]

5. Kim NN, Cox JD, Baggio RF, Emig FA, Mistry SK, Harper SL, Speicher DW, Morris SM, Ash DE, Traish A et al.. (2001) Probing erectile function: S-(2-boronoethyl)-L-cysteine binds to arginase as a transition state analogue and enhances smooth muscle relaxation in human penile corpus cavernosum. Biochemistry, 40 (9): 2678-88. [PMID:11258879]

6. Tenu JP, Lepoivre M, Moali C, Brollo M, Mansuy D, Boucher JL. (1999) Effects of the new arginase inhibitor N(omega)-hydroxy-nor-L-arginine on NO synthase activity in murine macrophages. Nitric Oxide, 3 (6): 427-38. [PMID:10637120]

7. Van Zandt MC, Whitehouse DL, Golebiowski A, Ji MK, Zhang M, Beckett RP, Jagdmann GE, Ryder TR, Sheeler R, Andreoli M et al.. (2013) Discovery of (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid and congeners as highly potent inhibitors of human arginases I and II for treatment of myocardial reperfusion injury. J Med Chem, 56 (6): 2568-80. [PMID:23472952]