In the central nervous system (CNS)of mammals, monoamine oxidase (EC 220.127.116.11)(MAO), which have been divided into two functional forms (MAO-A and MAO-B), and catechol-O-methyltransferase (EC 18.104.22.168)(COMT) act as catabolic enzymes of catecholamines and serotonin regulating their concentrations. In this study, the effects of guanidino compounds (5mM) on MAO-A, MAO-B and COMT were examined to invastigate the role of guanidino compounds in CNS function. MAO-A activity was decreased by α-guanidinoglutaric acid (GGA) and guanidinoethanesulfonic acid, and increased by arginine (Arg) and N-acetylarginine at a low substrate concentration (4.33μM). MAO-B activity was decreased by creatinine (CRN), δ-guanidinovaleric acid (GVA) and methylguanidine (MGua) at a high substrate concentration (3.125mM), and decreased by CRN, GVA, MGua, Arg, guanidine, 2-guanidinoethanol, β-guanidinopropionic acid, guanidinosuccinic acid and homoarginine at a low substrate concentration (62.5μM). GVA, CRN and MGua acted as competitive inhibitors on MAO-B and their calculated Ki values were 9.47mM, 14.5mM and 29.4mM, respectively. Although the guanidino compounds tested had no effect on COMT activity at a high substrate concentration (600μM), GSA and GVA inhibited COMT activity at a low substrate concentration (75μM). These results suggest that some guanidino compounds influence catabolic enzymes of indoleamine and catecholamines to control CNS function.
monoamine oxidase A
monoamine oxidase B