Peroxiredoxin
Encyclopedia
Peroxiredoxins are a ubiquitous family of antioxidant
enzyme
s that also control cytokine
-induced peroxide levels and thereby mediate signal transduction
in mammalian cells.
, redox
and possibly oligomerization states. They are divided into three classes: typical 2-Cys Prxs; atypical 2-Cys Prxs; and 1-Cys Prxs. These 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 thiol
s such as glutathione
, while the 1-Cys enzymes may be reduced by ascorbic acid
or glutathione in the presence of GST-π. Using crystal structures, a detailed catalytic cycle has been derived for typical 2-Cys Prxs, including a model for the redox-regulated oligomeric state proposed to control enzyme activity. Inactivation of these enzymes by over-oxidation 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). This family contains AhpC and TSA, as well as related proteins.
Mammals express six peroxiredoxins:
) as well as studies in knockout
mice. Mice lacking peroxiredoxin 1
or 2 develop severe haemolytic anemia, and are predisposed to certain haematopoietic
cancers. Peroxiredoxin 1 knockout mice have a 15% reduction in lifespan. Peroxiredoxin 6 knockout mice are viable and do not display obvious gross pathology, but are more sensitive to certain exogenous sources of oxidative stress, such as hyperoxia. Peroxiredoxin 3
(mitochondrial matrix peroxiredoxin) knockout mice are viable and do not display obvious gross pathology.
Plant 2-Cys peroxiredoxins are post-translationally targeted to chloroplasts, where they protect the photosynthetic membrane against photooxidative damage. Nuclear gene expression depends on chloroplast-to-nucleus signalling and responds to photosynthetic signals, such as the acceptor availability at photosystem II and ABA.
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that also control cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
-induced peroxide levels and thereby mediate signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
in mammalian cells.
Classification
Peroxiredoxins can be regulated by changes to phosphorylationPhosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
, redox
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
and possibly oligomerization states. They are divided into three classes: typical 2-Cys Prxs; atypical 2-Cys Prxs; and 1-Cys Prxs. These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
(the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid
Sulfenic acid
A sulfenic acid is an organosulfur compound and oxoacid with the general formula RSOH, where R ≠ H. Simple sulfenic acids, such as methanesulfenic acid, CH3SOH, are highly reactive and cannot be isolated in solution. In the gas phase the lifetime of methanesulfenic acid is about one minute...
by the peroxide substrate. The recycling of the sulfenic acid back to a thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
is what distinguishes the three enzyme classes, 2-Cys peroxiredoxins are reduced by thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
s such as glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
, while the 1-Cys enzymes may be reduced by ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
or glutathione in the presence of GST-π. Using crystal structures, a detailed catalytic cycle has been derived for typical 2-Cys Prxs, including a model for the redox-regulated oligomeric state proposed to control enzyme activity. Inactivation of these enzymes by over-oxidation of the active thiol to sulfinic acid can be reversed by sulfiredoxin
Sulfiredoxin
In enzymology, a sulfiredoxin is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are peroxiredoxin-, ATP, and a thiol, whereas its 4 products are peroxiredoxin-, ADP, phosphate, and a disulfide.This enzyme is involved in antioxidant metabolism by re-activating...
.
Peroxiredoxins are frequently referred to as alkyl hydroperoxide reductase (AhpC) in bacteria. Other names include thiol specific antioxidant (TSA). This family contains AhpC and TSA, as well as related proteins.
Mammals express six peroxiredoxins:
- 1-Cys enzymes: PRDX6PRDX6Peroxiredoxin-6 is a protein that in humans is encoded by the PRDX6 gene.- Function :The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites...
- 2-Cys enzymes: PRDX1Peroxiredoxin 1Peroxiredoxin-1 is a protein that in humans is encoded by the PRDX1 gene.-Interactions:Peroxiredoxin 1 has been shown to interact with PRDX4.-Further reading:...
, PRDX2Peroxiredoxin 2Peroxiredoxin-2 is a protein that in humans is encoded by the PRDX2 gene.-Further reading:...
, PRDX3PRDX3Thioredoxin-dependent peroxide reductase, mitochondrial is an enzyme that in humans is encoded by the PRDX3 gene.-Further reading:...
, PRDX4PRDX4Peroxiredoxin-4 is a protein that in humans is encoded by the PRDX4 gene.-Interactions:PRDX4 has been shown to interact with Peroxiredoxin 1.-Further reading:...
, and PRDX5PRDX5Peroxiredoxin-5, mitochondrial is a protein that in humans is encoded by the PRDX5 gene.-Further reading:...
Function
The physiological importance of peroxiredoxins is illustrated by their relative abundance (one of the most abundant proteins in erythrocytes after hemoglobin is peroxiredoxin 2Peroxiredoxin 2
Peroxiredoxin-2 is a protein that in humans is encoded by the PRDX2 gene.-Further reading:...
) as well as studies in knockout
Gene knockout
A gene knockout is a genetic technique in which one of an organism's genes is made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...
mice. Mice lacking peroxiredoxin 1
Peroxiredoxin 1
Peroxiredoxin-1 is a protein that in humans is encoded by the PRDX1 gene.-Interactions:Peroxiredoxin 1 has been shown to interact with PRDX4.-Further reading:...
or 2 develop severe haemolytic anemia, and are predisposed to certain haematopoietic
Haematopoiesis
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells...
cancers. Peroxiredoxin 1 knockout mice have a 15% reduction in lifespan. Peroxiredoxin 6 knockout mice are viable and do not display obvious gross pathology, but are more sensitive to certain exogenous sources of oxidative stress, such as hyperoxia. Peroxiredoxin 3
PRDX3
Thioredoxin-dependent peroxide reductase, mitochondrial is an enzyme that in humans is encoded by the PRDX3 gene.-Further reading:...
(mitochondrial matrix peroxiredoxin) knockout mice are viable and do not display obvious gross pathology.
Plant 2-Cys peroxiredoxins are post-translationally targeted to chloroplasts, where they protect the photosynthetic membrane against photooxidative damage. Nuclear gene expression depends on chloroplast-to-nucleus signalling and responds to photosynthetic signals, such as the acceptor availability at photosystem II and ABA.
Circadian clock
Peroxiredoxins are the oldest common mechanism responsible for the 24-hour internal circadian clock of almost all life on earth.See also
- PeroxidasePeroxidasePeroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...
- CatalaseCatalaseCatalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...
- Oxidative stressOxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
- Reactive oxygen speciesReactive oxygen speciesReactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
- superoxide dismutaseSuperoxide dismutaseSuperoxide dismutases are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen...
- Peroxiredoxin classification indexPeroxiredoxin classification indexPeroxiRedoxin classification indEX is a database of peroxiredoxins classified into one of six distinct subfamilies....