L-Arginine serves as a common substrate for both nitric oxide synthase (NOS) and arginase in the cell. NOS catalyzes the oxidation of arginine to citrulline and NO with Nω-hydroxy-L-arginine (NOHA) formed as an intermediate. Arginase, on the other hand, catalyzes the hydrolysis of arginine into urea and L-ornithine. BEC is a potent slow-binding competitive inhibitor of recombinant rat liver arginase I with a Ki of 0.4-0.6 μM. It is also a potent inhibitor of human arginase II with Ki values of 0.31 μM and 30 nM at pH 7.5 and 9.5, respectively. It does not inhibit murine iNOS at concentrations up to 1 mM. BEC significantly enhances NO-dependent relaxation of human penile corpus canvernosum smooth muscle in vitro at concentrations between 0.1-1.0 mM.
ChEBI: S-(2-boronoethyl)-L-cysteine is l-cysteine substituted at sulfur by a 2-boronoethyl group. It is an organoboron compound, a L-cysteine thioether and a non-proteinogenic L-alpha-amino acid.
BEC (S-(2-boronoethyl)-l-cysteine) is a potent and specific arginase inhibitor that restores flow-induced responses in arterioles from diabetic rats.
This boronic acid-containing arginine analogue (FW = 190.00 g/mol; CAS 63107-40-4; Abbreviation: BEC) is a slow, tight-binding competitive inhibitor of arginase (Reaction: L-Arginine + H2O ? Urea + L-Ornithine), the binuclear manganese metalloenzyme catalyzing the last step in the Urea Cycle. Upon binding, the boronic acid moiety undergoes nucleophilic attack by the enzyme’s metal-bridging hydroxide ion, yielding a tetrahedral boronate anion that bridges the binuclear manganese cluster and mimics the tetrahedral intermediate (or a flanking transition state configuration) in arginase catalysis. BEC is also a potent inhibitor of human arginase II with Ki values of 0.31 μM and 30 nM at pH 7.5 and 9.5, respectively. Inhibition of arginase by BEC increases the circulating concentration of arginine, thereby increasing nitric oxide synthesis and significantly enhancing NO-dependent smooth muscle relaxation in human penile corpus cavernosum. Arginase is thus a potential druggable target for the treatment of erectile dysfunction.
