Peroxiredoxins (Prxs, ; HGNC root symbol PRDX) (pronounced per-ox-er-dox-in) are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells. The family members in humans are PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, and PRDX6. The physiological importance of peroxiredoxins is illustrated by their relative abundance (one of the most abundant proteins in erythrocytes after hemoglobin is peroxiredoxin 2).
ClassificationPrxs were historically divided into three (mechanistic) classes:
- Typical 2-Cys Prxs
- Atypical 2-Cys Prxs and
- 1-Cys Prxs.
Catalytic cycleThese enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid by the peroxide substrate. The recycling of the sulfenic acid back to a thiol is what distinguishes the three enzyme classes. 2-Cys peroxiredoxins are reduced by thiols such as thioredoxins, thioredoxin-like proteins, or possibly glutathione, while the 1-Cys enzymes may be reduced by ascorbic acid or glutathione in the presence of GST-π. Using high resolution crystal structures, a detailed catalytic cycle has been derived for Prxs, including a model for the redox-regulated oligomeric state proposed to control enzyme activity. Inactivation of these enzymes by over-oxidation (also known as hyperoxidation) of the active thiol to sulfinic acid can be reversed by sulfiredoxin. Peroxiredoxins are frequently referred to as alkyl hydroperoxide reductase (AhpC) in bacteria. Other names include thiol specific antioxidant (TSA) and thioredoxin peroxidase (TPx). Mammals express six peroxiredoxins:
- 1-Cys enzymes: PRDX6 (in the Prx6 group)
- 2-Cys enzymes: PRDX1, PRDX2, PRDX3, PRDX4 (all four in the Prx1 group), and PRDX5 (in the Prx5 group)
Enzyme regulationPeroxiredoxins can be regulated by phosphorylation, redox status, acetylation, nitration, truncation and oligomerization states.
FunctionPeroxiredoxin uses thioredoxin (Trx) to recharge after reducing hydrogen peroxide (H2O2) in the following reactions:
- Prx(reduced) + H2O2 → Prx(oxidized) + 2H2O
- Prx(oxidized) + Trx(reduced) → Prx(reduced) + Trx(oxidized)
Circadian clockPeroxiredoxins have been implicated in the 24-hour internal circadian clock of many organisms.
- Oxidative stress
- Peroxiredoxin classification index
- Reactive oxygen species
- Superoxide dismutase