title: Naturally-occurring tetrahydro-β-carboline alkaloids derived from tryptophan are oxidized to bioactive β-carboline alkaloids by heme peroxidases.
abstract: β-Carbolines are indole alkaloids that occur in plants, foods, and endogenously in mammals and humans, and which exhibit potent biological, psychopharmacological and toxicological activities. They form from naturally-occurring tetrahydro-β-carboline alkaloids arising from tryptophan by still unknown way and mechanism. Results in this research show that heme peroxidases catalyzed the oxidation of tetrahydro-β-carbolines (i.e. 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid) into aromatic β-carbolines (i.e. norharman and harman, respectively). This oxidation followed a typical catalytic cycle of peroxidases through redox intermediates I, II, and ferric enzyme. Both, plant peroxidases (horseradish peroxidase, HRP) and mammalian peroxidases (myeloperoxidase, MPO and lactoperoxidase, LPO) catalyzed the oxidation in an efficient manner as determined by kinetic parameters (VMAX and KM). Oxidation of tetrahydro-β-carbolines was inhibited by peroxidase inhibitors such as sodium azide, ascorbic acid, hydroxylamine and excess of H2O2. The formation of aromatic β-carbolines by heme peroxidases can help to explain the presence and activity of these compounds in biological systems.
authors.affiliation: Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN-CSIC), Spanish National Research Council (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. Electronic address: tomas.herraiz@csic.es.
authors.forename: Tomás
authors.initials: T
authors.lastname: Herraiz
authors.affiliation: Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN-CSIC), Spanish National Research Council (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Galisteo
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D002243:Carbolines / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000737:chemistry; D006418:Heme; D006735:Horseradish Peroxidase / Q000737:chemistry; D019811:Hydroxylamine / Q000494:pharmacology; D007700:Kinetics; D007784:Lactoperoxidase / Q000737:chemistry; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D019810:Sodium Azide / Q000494:pharmacology; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D002243:Carbolines; D004791:Enzyme Inhibitors; D019811:Hydroxylamine; D006418:Heme; D006247:Harmine; C038114:1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid; C054910:1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid; C005010:harman; D014364:Tryptophan; C010262:norharman; D019810:Sodium Azide; D006735:Horseradish Peroxidase; D007784:Lactoperoxidase; D010544:Peroxidases; D009195:Peroxidase; D001205:Ascorbic Acid
keywords: Alkaloids; Horseradish peroxidase; Lactoperoxidase; Myeloperoxidase; Tetrahydro-β-carboline; β-Carboline