Nitrosation of melatonin by nitric oxide and peroxynitrite.
Peroxynitrite (ONOO-) is an endogenous molecule, formed by rapid coupling between *NO and O2*-. ONOO- is known to be a strong oxidant of thiols and metalloorganic compounds and also a nitrating agent of aromatic compounds such as tyrosine. However, its chemistry is not yet well elucidated under physiological conditions. Melatonin, which is an indole-amine produced by the pineal gland and other organs, has antioxidant properties. We show that melatonin reacts with ONOO- in phosphate-buffered solutions. We provide evidence of nitrosation and oxidation at the pyrrole nitrogen leading to 1-nitrosomelatonin and 1-hydroxymelatonin, these being the major reactions in aqueous phosphate-buffered solutions besides other aromatic hydroxylations and nitration. 4-Nitromelatonin is formed, but in small amounts. The kinetics of all transformations were strictly dependent on ONOO- decay, whereas yields varied with pH and the presence of CO2. The N-oxidation became competitive with nitrosation at pH 7.4, in medium containing a sufficient amount of CO2. A proposed mechanism involves the transient formation of melatonyl radical and ONOO* radical derived from ONOO- decay.
Blanchard
B
B
Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France.
Pompon
D
D
Ducrocq
C
C
D000975:Antioxidants / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D008550:Melatonin / Q000737:chemistry*; D009566:Nitrates / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D015538:Nitrosation; D010084:Oxidation-Reduction
D000975:Antioxidants; D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; D008550:Melatonin