About Peroxiredoxin / PRDX:
Peroxiredoxins (Prx) are a family of antioxidant enzymes. They are also widely referred to as are Thiol Specific Antioxidants (TSA), Thioredoxin Peroxidase (TPx). They are often referred to as Alkyl Hydroperoxide Reductase (AhpC) in bacteria.
They are widely regarded as effective guardians against oxidative stress and have important anti-inflammatory properties. They also help to control cytokine-induced peroxide levels. This means that they help to mediate signal transduction in the cells of humans and other mammals. They have also been linked to the circadian clocks or rhythms of humans and other mammals, playing a part in their natural sleeping cycles.
They are fairly abundant in human physiology which speaks to their importance. For instance, Prx2 is the second most abundant protein in human red blood cells (with the first, of course, being haemoglobin). Here we’ll look at the mechanisms that peroxiredoxins facilitate, their interactions and functions in the real world and their structures.
All peroxiredoxins share the same catalytic mechanism regardless of which family they come from.
In all cases the peroxidatic cysteine (which is redox-active) in the active site is oxidized by the peroxide substrate to a sulfenic acid, recycling the sulfenic acid back to a thiol (an organosulfur compound).
Indeed, the defining trait of a Peroxiredoxin is how it recycles the sulfenic acid back to a thiol and this plays a big part in distinguishing the three enzyme classes.
2-Cys peroxiredoxins are reduced by different thiols like thioredoxins and other thioredoxin-like proteins, or even glutathione.
1-Cys enzymes can also be reduced by glutathione as well as ascorbic acid in the presence of Glutathione S-transferase (GST). Over-oxidation (also known as hyperoxidation) of the active thiol can lead to inactivation of these enzymes although this can be reversed by sulfiredoxin.
PRDX Interactions and Functions
Peroxiredoxins have a range of interactions and reactions. After reduced and oxidised reactions they will often use Thioredoxin (Trx) to recharge. This often takes place in the following reactions:
Prx (reduced) + H2O2 → Prx(oxidized) + 2H2O
Pex (oxidized) + Trx(reduced) → Prx(reduced) + Trx(oxidized)
Studies using mice demonstrate the importance of Prx. Mice found to be lacking in Prx1 or 2 were found to develop severe haemolytic anemia. They even demonstrated an alarming predisposition to certain haematopoietic cancers. Peroxiredoxin 1 knockout mice (genetically modified mice with the enzyme eliminated from their genetic code) had a 15% reduction in lifespan. While Peroxiredoxin 6 knockout mice did not display obvious pathology, they demonstrated an increased sensitivity to oxidative stresses like hyperoxia.
Peroxiredoxin 3 (mitochondrial matrix peroxiredoxin) knockout mice were shown to be viable with no obvious gross pathology. Peroxiredoxins were proposed to play a role in cell signaling via the regulation of H2O2 levels.
The family members in the cells of humans and other mammals are called Prx1, Prx2, Prx3, Prx4, Prx5, and Prx6. They are divided into three classes- typical 2-Cys Prxs, atypical 2-Cys Prxs, and 1-Cys Prxs. The resolving cysteine, CR, which forms an intersubunit disulfide bond with CP can reside in multiple positions in Prx’s structures, leading to the addition of the "atypical 2-Cys Prx" category.