Nitrotyrosine (nitrosative stress)

3-Nitrotyrosine arises when peroxynitrite (ONOO⁻) — from the reaction of nitric oxide (NO) with superoxide — modifies tyrosine residues in proteins. It is used as a marker of nitrosative stress, which damages mitochondria, enzymes and DNA. Raised values have been observed in studies with chronic inflammation and in smokers; a link with long COVID is being investigated. Measured from EDTA blood — a practice visit is required.

What nitrotyrosine shows

Nitric oxide (NO) is a messenger that widens blood vessels, transmits nerve signals and helps immune cells kill pathogens; the NO synthases make it from the amino acid arginine. When NO and superoxide – a by-product of the respiratory chain and of immune cells – meet, they react extremely quickly to form peroxynitrite. Peroxynitrite and the radicals derived from it attach a nitro group to the amino acid tyrosine in proteins; this produces 3-nitrotyrosine. The immune cell enzyme myeloperoxidase can also alter tyrosine in this way. Because the change is stable and hardly reversed, it serves as a trace of how many reactive nitrogen compounds have been formed. Free nitrotyrosine is broken down, among other things, into 4-hydroxy-3-nitrophenylacetic acid and excreted in urine.

Low nitrotyrosine – what does it mean?

A low value shows that little peroxynitrite is being formed: superoxide dismutase rapidly neutralises superoxide before it can react with NO, and NO remains available for its tasks as a messenger – for example widening the blood vessels. Proteins in cells and mitochondria are then hardly altered by nitration.

High nitrotyrosine – what happens in the body?

A high value shows that more peroxynitrite is being formed – usually because a lot of NO and a lot of superoxide are produced at the same time, as with activated immune cells during inflammation. Nitration alters the function of proteins: affected are, among others, enzymes of the respiratory chain, structural proteins and mitochondrial superoxide dismutase, which is itself inhibited as a result. Peroxynitrite also oxidises tetrahydrobiopterin, a cofactor of the NO synthases; without it, these enzymes produce more superoxide instead of NO, and the cycle reinforces itself. NO is then lacking for widening the blood vessels, and the mitochondria produce less ATP. Raised values have been observed in studies with chronic inflammation, diabetes, cardiovascular disease and in smokers.

The interpretation is given in your report.