Nitrotyrosine is a product of

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

nitration In organic chemistry, nitration is a general class of chemical processes for the introduction of a nitro group into an organic compound. The term also is applied incorrectly to the different process of forming nitrate esters between alcohols and ...

mediated by

reactive nitrogen species Reactive nitrogen species (RNS) are a family of antimicrobial molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 ( NOS2) and NADPH oxidase respectivel ...

such as

peroxynitrite Peroxynitrite (sometimes called peroxonitrite) is an ion with the formula ONOO−. It is a structural isomer of nitrate, Preparation Peroxynitrite can be prepared by the reaction of superoxide with nitric oxide: : It is prepared by the react ...

anion and

nitrogen dioxide Nitrogen dioxide is a chemical compound with the formula . It is one of several nitrogen oxides. is an intermediate in the industrial synthesis of nitric acid, millions of tons of which are produced each year for use primarily in the producti ...

. 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. 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 Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

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 Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

. In all these studies nitrotyrosine was undetected in healthy subjects. Nitrotyrosine is also found in numerous other disease-affected tissues, such as the

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

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 Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

. Research shows that nitrotyrosine levels can be reduced by N-acetyl cysteine, which is a precursor to

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

, 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

{{reflist, 2 Nitro compounds Amino acids