Nitrotyrosine is a product of
tyrosine nitration 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 (O
2−) and NO forming peroxynitrite (ONOO
−) a destructive free radical oxidant. 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
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,
septic shock
Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Con ...
and
coeliac disease. 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
Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. Usu ...
.
Peroxynitrite and/or nitrative stress may participate in the pathogenesis of
diabetes.
Research shows that nitrotyrosine levels can be reduced by
N-acetyl cysteine
Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...
, which is a precursor to
glutathione, one of the body's primary
endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, es ...
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
s. Nitrotyrosine levels have been linked to cerebral ischemia and edema, for which NAC has also been proven as a potential treatment.
Free nitrotyrosine undergoes metabolism to form 3-nitro-4-hydroxyphenylacetic acid (NHPA) which is excreted in the urine.
Nitrotyrosine, as a marker of reactive oxygen species, has also been linked to degeneration of dopamine neurons.
Tyrosine is the precursor to
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
, a
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
that's important for motivation, attention, learning, circadian rhythms, and other biological processes.
References
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Nitro compounds
Amino acids