title: Oxidation of melatonin by oxoferryl hemoglobin: a mechanistic study.
abstract: Reaction of melatonin with the hypervalent iron centre of oxoferryl hemoglobin, produced in aqueous solution from methemoglobin and H2O2, has been investigated at 37 degrees C and pH 7.4, by absorption spectroscopy. The reaction results in reduction of the oxoferryl moiety with formation of a heme-ferric containing hemoprotein. Stopped-flow spectrophotometric measurements provide evidence that the reduction of oxoferryl-Hb by melatonin is first-order in oxoferryl-Hb and first-order in melatonin. The bimolecular reaction constant at pH 7.4 and 37 degrees C is 112 +/- 1.0 M(-1) s(-1). Two major oxidation products from melatonin have been found by gas chromatography-mass spectroscopy: the cyclic compound 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-3a-hydroxypyrrolo[2,3-b]indole (cyclic 3-hydroxy-melatonin), and N-acetyl-N'-formyl 5-methoxykynuramine (AFMK). The percentage yield of the two major products appears dependent on the ratio [oxoferryl-Hb]:[melatonin]--the higher the ratio the higher the yield of AFMK. The observed stoichiometry oxoferryl-Hb(reduced):melatonin(consumed) is 2, when the ratio [oxoferryl-Hb]:[melatonin] is 1:1, but appears >2 at higher molar ratios. The reduction of the hypervalent iron of the oxoferryl moiety may be consistent with an oxidation of melatonin by two one-electron steps.
authors.affiliation: Department of Pharmaceutical Toxicological and Biological Chemistry, University of Palermo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Tesoriere
authors.forename: G
authors.initials: G
authors.lastname: Avellone
authors.forename: L
authors.initials: L
authors.lastname: Ceraulo
authors.forename: D
authors.initials: D
authors.lastname: D'Arpa
authors.forename: M
authors.initials: M
authors.lastname: Allegra
authors.forename: M A
authors.initials: MA
authors.lastname: Livrea
mesh_terms: D000818:Animals; D002417:Cattle; D002713:Chlorine / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D007735:Kynuramine / Q000031:analogs & derivatives / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008550:Melatonin / Q000378:metabolism*; D008706:Methemoglobin / Q000378:metabolism; D010084:Oxidation-Reduction; D010087:Oxides / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D010087:Oxides; D007735:Kynuramine; D002713:Chlorine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D008706:Methemoglobin; C041955:tetrachlorodecaoxide; D006861:Hydrogen Peroxide; D008550:Melatonin