Catecholamine-induced release of nitric oxide from N-nitrosotryptophan derivatives: a non-enzymatic method for catecholamine oxidation.
In recent years, interest in the physiological functions of S-nitrosothiols has strongly increased owing to the potential of these compounds to release nitric oxide. In contrast, little is known about similar functions of N-nitrosated (N-terminal-blocked) tryptophan derivatives, which can be also formed at physiological pH. Utilizing N-acetyl-N-nitrosotryptophan (NANT) and N-nitrosomelatonin (NOMela) as model compounds, we have studied their reaction with catechol and catecholamines such as epinephrine and dopamine. In these reactions, NANT was quantitatively converted to N-acetyltryptophan (NAT), and nitric oxide was identified as a volatile product. During this process, ortho-semiquinone-type radical anions deriving from catechol and dopamine, were detected by ESR spectrometry. The catechol radical concentration was about eight times higher under normoxia than under hypoxia and a similar relationship was found for the decay rates of NANT under these conditions. An epinephrine-derived oxidation product, namely adrenochrome, but not a catechol-derived one, was identified. These observations strongly indicate that N-nitrosotryptophan derivatives transfer their nitroso-function to an oxygen atom of the catecholamines, and that the so-formed intermediary aryl nitrite may decompose homolytically with release of nitric oxide, in addition to a competing hydrolysis reaction to yield nitrite and the corresponding catechol. These conclusions were supported by quantum chemical calculations performed at the CBS-QB3 level of theory. Since nitric oxide is non-enzymatically released from N-nitrosotryptophan derivatives on reaction with catecholamines, there might be a possibility for the development of epinephrine-antagonizing drugs in illnesses like hypertension and pheochromocytoma.
Kytzia
Anna
A
Institut für Physiologische Chemie, Universitätsklinikum Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Korth
Hans-Gert
HG
de Groot
Herbert
H
Kirsch
Michael
M
D002395:Catecholamines / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D004837:Epinephrine / Q000737:chemistry; D008722:Methods; D009569:Nitric Oxide / Q000737:chemistry*; D009603:Nitroso Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen; D011789:Quantum Theory; D014364:Tryptophan / Q000737:chemistry
D002395:Catecholamines; D009603:Nitroso Compounds; D009569:Nitric Oxide; D014364:Tryptophan; D010100:Oxygen; D004837:Epinephrine