Nitration and hydroxylation of aromatic amino acid and guanine by the air pollutant peroxyacetyl nitrate.
Peroxyacetyl nitrate (PAN) is a common gaseous photochemical compound in polluted air and cigarette smog. The toxicity of PAN has been found to depend on three pathways: (1) its oxidizing property that mimics peroxide or peroxynitrite; (2) its nitrating and hydroxylating properties similar to peroxynitrite; and (3) its acetylating property like acetic anhydride. The present investigations were intended to focus on the reactions of PAN with aromatic amino acids and guanine. When PAN interacted with tyrosine and guanine the major products were 3-nitrotyrosine, 3, 5-dinitrotyrosine, 8-hydroxyguanine and 8-nitroguanine. These compounds have been used as indicators for the presence of peroxynitrite in previous studies. When PAN interacted with phenylalanine, the products were 3-nitrotyrosine, 4-nitrophenylalanine, p-tyrosine, o-tyrosine and m-tyrosine. 5-Hydroxytryptophan is produced from the reaction of PAN with tryptophan. Furthermore, the formation of nitrated tyrosines was also found in the PAN-treated HL-60 cells. A high yield of dityrosine was formed when PAN and peroxynitrite were reacted with tyrosine, probably through free radical oxidation. We also found that peroxynitrite and PAN are similar in their oxidizing activity. From these findings, we suggest that peroxynitrite may be considered as the reactive intermediate of PAN.
Lin
J K
JK
Institute of Biochemistry, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-ai Road, Taipei, Taiwan, ROC. jklin@ha.mc.ntu.edu.tw
Chen
K J
KJ
Liu
G Y
GY
Chu
Y R
YR
Lin-Shiau
S Y
SY
D000393:Air Pollutants / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000598:Amino Acids, Cyclic / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006147:Guanine / Q000737:chemistry / Q000378:metabolism*; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D013058:Mass Spectrometry; D009566:Nitrates / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D009584:Nitrogen / Q000737:chemistry / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000633:toxicity; D010463:Peracetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism
D000393:Air Pollutants; D000598:Amino Acids, Cyclic; D009566:Nitrates; D016877:Oxidants; C107610:3,5-dinitrotyrosine; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D010649:Phenylalanine; D006147:Guanine; D014364:Tryptophan; D010463:Peracetic Acid; D009584:Nitrogen; C004185:peroxyacetyl nitrate