Oxidative and nitrative modifications of enkephalins by reactive nitrogen species.
The interaction of Leucine-enkephalin (Leu-enkephalin) with reactive nitrogen species has been investigated. Reactive nitrogen species are capable of nitrating and oxidizing Leu-enkephalin. HPLC analysis shows the formation of two major enkephalin derivatives by peroxynitrite. The tyrosine amino-terminal residue of Leu-enkephalin is converted either to 3-nitrotyrosine thus producing nitroenkephalin and to dityrosine by dimerization with the production of an enkephalin dimer. The evidence of the formation of the nitroenkephalin and of the enkephalin dimer--dienkephalin--was achieved by electrospray ionisation mass spectrometry. In addition to peroxynitrite, the methylene blue photosensitized oxidation of enkephalin in the presence of nitrite leads to the formation of the nitrated peptide. Moreover, the nitropeptide can be also obtained by peroxidase-generated nitrogen reactive species.
Fontana
Mario
M
Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Università degli Studi di Roma "La Sapienza", Rome, Italy. mario.fontana@uniroma1.it
Pecci
Laura
L
Schininá
Maria Eugenia
ME
Montefoschi
Gabriella
G
Rosei
Maria Anna
MA
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D004743:Enkephalin, Leucine / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009573:Nitrites / Q000737:chemistry; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000138:chemical synthesis / Q000378:metabolism; D010777:Photochemistry; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D026082:Singlet Oxygen / Q000378:metabolism; D017693:Sodium Bicarbonate / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
D009573:Nitrites; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; D026082:Singlet Oxygen; D004743:Enkephalin, Leucine; D017693:Sodium Bicarbonate; D009195:Peroxidase