Nitrotyrosine is a product of
tyrosinenitration mediated by
reactive nitrogen species such as
peroxynitrite anion and
nitrogen dioxide. Nitrotyrosine is identified as an indicator or marker of cell damage, inflammation as well as NO (nitric oxide) production. Nitrotyrosine is formed in the presence of the active metabolite NO. Generally in many disease states, oxidative stress increases the production of superoxide (O2−) and NO forming peroxynitrite (ONOO−) a destructive free radical oxidant.[2] The production of ONOO− is capable of oxidizing several lipoproteins and of nitrating tyrosine residues in many proteins. It is difficult to determine the production of ONOO− so, usually nitrotyrosine in proteins are the detectable marker for indirectly detecting ONOO−. It is detected in large number of pathological conditions[3][4] and is considered a marker of NO-dependent, reactive nitrogen species-induced nitrative stress. Nitrotyrosine is detected in biological fluids such as plasma, lung aspirants-BALF (Broncho alveolar lining fluid) and urine. Increased level of nitrotyrosine is detected in
rheumatoid arthritis,[5]septic shock[6] and
coeliac disease.[7] In all these studies nitrotyrosine was undetected in healthy subjects. Nitrotyrosine is also found in numerous other disease-affected tissues, such as the
cornea in
keratoconus.[8] Peroxynitrite and/or nitrative stress may participate in the pathogenesis of
diabetes.[4][9]
Research shows that nitrotyrosine levels can be reduced by
N-acetyl cysteine,[10][11] which is a precursor to
glutathione, one of the body's primary
endogenousantioxidants. Nitrotyrosine levels have been linked to cerebral ischemia and edema, for which NAC has also been proven as a potential treatment.[12]
Free nitrotyrosine undergoes metabolism to form 3-nitro-4-hydroxyphenylacetic acid (NHPA) which is excreted in the urine.[13][14]
Nitrotyrosine, as a marker of reactive oxygen species, has also been linked to degeneration of dopamine neurons.[15] Tyrosine is the precursor to
dopamine, a
neurotransmitter that's important for motivation, attention, learning, circadian rhythms, and other biological processes.
^Fukuyama N, Takebayashi Y, Hida M, Ishida H, Ichimori K, Nakazawa H (1997). "Clinical evidence of peroxynitrite formation in chronic renal failure patients with septic shock". Free Radical Biology & Medicine. 22 (5).
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10.1016/S0891-5849(96)00401-7.
PMID9119244.
^ter Steege JC, Koster-Kamphuis L, van Straaten EA, Forget PP, Buurman WA (November 1998). "Nitrotyrosine in plasma of celiac disease patients as detected by a new sandwich ELISA". Free Radical Biology & Medicine. 25 (8): 953–963.
doi:
10.1016/s0891-5849(98)00184-1.
PMID9840741.
^Ohshima H, Friesen M, Brouet I, Bartsch H (September 1990). "Nitrotyrosine as a new marker for endogenous nitrosation and nitration of proteins". Food and Chemical Toxicology. 28 (9): 647–652.
doi:
10.1016/0278-6915(90)90173-k.
PMID2272563.