Unraveling the Peroxidase Activity in Peroxiredoxins: A Comprehensive Review of Mechanisms, Functions, and Biological Significance

Abstract

Peroxiredoxins (Prxs) are members of the antioxidant enzymes necessary for every living object in the three domains of life and play critical roles in controlling peroxide levels in cells. This comprehensive literature review aims to elucidate the peroxidase activity of Prxs, examining their roles and significance for organisms across various taxa. Ironically, the primary role of the Prxs is the peroxidase activity, which comprises the reduction of hydrogen peroxide and other organic hydroperoxides and decreases the risk of oxidative damage in the cells. The above enzymatic activity occurs through the reversible oxidation-reduction catalyzed by cysteine residues in the active site by forming sulfenic acid and reduction by intracellular reductants. Structurally and functionally, Prxs function as dimers or decamers and show different catalytic patterns according to their subfamilies or cellular compartments. Compared to the mechanisms of the other two subgroups of Prxs, including 2-Cys Prxs and atypical Prxs, the 1-Cys Prxs have monomer-dimer switch folding coupled with catalytic activity. In addition to their peroxidase activity, which is widely known, Prxs are becoming acknowledged to be involved in other signaling processes, including redox signaling and apoptosis. This aversion to oxidative stress and regulation by the cellular redox state places them at the heart of adaptive cellular responses to changes in the environment or manifestations of diseases. In conclusion, based on the data obtained and on furthering the knowledge of Prxs' structure and function, these enzymes may be classified as a diverse yet essential family of proteins that can effectively protect cells from the adverse effects of oxidative stress due to peroxidase activity. This indicates secondary interactions, summarized as peroxide detoxification or regulatory signaling, and identifies their applicability in multiple biological pathways. Such knowledge is valuable for enhancing the general comprehension of essential cellular functions and disclosing further therapeutic approaches to the diseases caused by the increased production of reactive oxygen species.

Keywords: oxidative stress; pathways; peroxidase; peroxiredoxins; redox balance.

Figure 1. Peroxiredoxin family: subclasses of PRDXs

This image was created by the author. Cys, cysteine; SpOH, commonly stands for serine-phosphoethanolamine; SRH, serine racemase homologue; Prdx6, peroxiredoxin 6.

Figure 2. The above diagrams show the catalytic mechanism of typical 2-Cys PRDX

This image is the author's own creation. 2-Cys PRDX-2: Cysteine Peroxiredoxin; SPOH: Sulfiredoxin Peroxidatic Cysteine; SRH: Sulfonic Acid; SP: Peroxidatic Cysteine; SR: Resolving Cysteine

Figure 3. The above diagram show the catalytic mechanism of atypical 2-Cys PRDX

This image is the author's own creation. 2-Cys PRDX-2: Cysteine Peroxiredoxin; SPOH: Sulfiredoxin Peroxidatic Cysteine; SRH: Sulfonic Acid; SP: Peroxidatic Cysteine; SR: Resolving Cysteine

Figure 4. The above diagram shows the catalytic mechanism of 1-Cys PRDX

This image is the author's own creation. 2-Cys PRDX-2: Cysteine Peroxiredoxin; SPOH: Sulfiredoxin Peroxidatic Cysteine; SRH: Sulfonic Acid; SP: Peroxidatic Cysteine; SR: Resolving Cysteine

Figure 5. Description of normal and dysfunctional cellular processes contributed by redox imbalance

This image is the author's own creation. ROS: Reaction oxygen species; ER: Endoplasmic reticulum

Figure 6. Common pathogenic features of neurodegenerative illnesses include cell malfunction, neuronal death, and the buildup of specific proteins that form insoluble aggregates inside and/or between neurons

This image is the author's creation. α-syn: alpha-synuclein; Aβ: Amyloid-beta; mHTT: mutant huntingtin protein