Effects of norlaudanosolinecarboxylic acids on enzymes of catecholamine metabolism.
Enzymes involved in catecholamine metabolism were assayed in the presence of a new class of naturally occurring tetrahydroisoquinoline alkaloids, the norlaudanosolinecarboxylic acids (NLCAs). NLCAs inhibited tyrosine hydroxylase noncompetitively with respect to its substrate, tyrosine and the cofactor, 6-methyltetrahydropterin (NLCA Kj = 4 x 10(-4) M; 3',4'-deoxynorlaudanosolinecarboxylic acid (DNLCA) Kj = 1.5 x 10(-4) M). Adrenal dopamine-beta-hydroxylase was also inhibited by NLCAs [3'O-methylnorlaudanosolinecarboxylic acid (MNLCA) Kj = 1.2 x 10(-4) M] and NLCA is a competitive inhibitor of norepinephrine methylation by hepatic catechol-O-methyltransferase (NLCA Kj = 5.6 x 10(-5) M). While a slight reduction of rat adrenal monoamine oxidase by MNLCA was also observed, NLCA did not affect the oxidation of tyrosine by D-amino acid oxidase. Kinetic patterns of tyrosine aminotransferase and aromatic amono acid decarboxylase from rat liver were not altered by addition of 1 to 10 x 10(-5) M NLCA or its 3'-O-methyl ether (MNLCA). In vivo studies of brain tyrosine metabolism in mouse neonates corroborated results on the in vitro effect of DNLCA on tyrosine hydroxylase. The potential of high-pressure liquid chromatography was demonstrated in both enzyme assays and radiometric studies of in vivo metabolism.
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000502:physiology; D001681:Biological Assay; D002264:Carboxylic Acids / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines / Q000378:metabolism*; D003067:Coenzymes / Q000502:physiology; D003605:D-Amino-Acid Oxidase / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010208:Papaverine / Q000031:analogs & derivatives*; D051381:Rats; D013765:Tetrahydropapaveroline / Q000494:pharmacology*; D000637:Transaminases / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors
D002264:Carboxylic Acids; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D003067:Coenzymes; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D008996:Monoamine Oxidase Inhibitors; D013765:Tetrahydropapaveroline; D010208:Papaverine; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D003605:D-Amino-Acid Oxidase; D000637:Transaminases; D001142:Aromatic-L-Amino-Acid Decarboxylases