Glutathione peroxidase (GP Glutathione peroxidase , PDB 1GP1 , EC 1.11.1.9 ) is a family of enzymes that protect the body from oxidative damage. Glutathione peroxidase catalyzes the reduction of lipid hydroperoxides to the corresponding alcohols and the reduction of hydrogen peroxide to water. Several genes encoding different forms are known glutathione peroxidases, which differ in localization in the body, in mammals and humans, a significant part of the enzymes of this family are selenium-containing tetrameric proteins and glycoprotein s , there are also monomeric and non-selenium forms [1] .
| Glutatin Peroxidase 1 | |
|---|---|
 | |
| Designations | |
| Characters | GPX1 |
| Entrez gene | 2876 |
| Hgnc | 4553 |
| Omim | 138320 |
| Refseq | NM_000581 |
| Uniprot | P07203 |
| Other data | |
| Cipher cf | 1.11.1.9 |
| Locus | 3rd hr. , 3p21.3 |
| glutathione peroxidase 3 (found in blood plasma) | |
|---|---|
| Designations | |
| Characters | GPX3 |
| Entrez gene | 2878 |
| Hgnc | 4555 |
| Omim | 138321 |
| Refseq | NM_002084 |
| Uniprot | P22352 |
| Other data | |
| Cipher cf | 1.11.1.9 |
| Locus | 5th hr , 5q23 |
| glutathione peroxidase 5 (epidermal, androgen-bound protein) | |
|---|---|
| Designations | |
| Characters | GPX5 |
| Entrez gene | 2880 |
| Hgnc | 4557 |
| Omim | 603435 |
| Refseq | NM_001509 |
| Uniprot | O75715 |
| Other data | |
| Cipher cf | 1.11.1.9 |
| Locus | 6th , 6p21.32 |
| glutathione peroxidase 6 (visual system) | |
|---|---|
| Designations | |
| Characters | GPX6 |
| Entrez gene | 257202 |
| Hgnc | 4558 |
| Omim | 607913 |
| Refseq | NM_182701 |
| Uniprot | P59796 |
| Other data | |
| Cipher cf | 1.11.1.9 |
| Locus | 6th , 6p21 |
Content
Isoenzymes
There are several isoenzymes that are encoded by different genes . Isoenzymes differ in localization in the cell and substrate specificity . In humans, 8 forms of GPx are distinguished, 5 of which are selenium-dependent (selenium is part of the active center) [1] . Glutathione peroxidase 1 (GPx1) is the tetrameric form, the most common form of the enzyme, and was found in the cytoplasm of almost all mammalian tissues , both hydrogen peroxide and many organic hydroperoxides are the substrate GPx1. Glutathione peroxidase 2 (GPx2) is also a tetrameric enzyme expressed in the intestine. The highest concentrations of this enzyme were found at the base of the intestinal crypts. In embryogenesis, expression of a gene encoding GPx2 predominates in fast-growing tissues [1] . GPx3 is an extracellular tetrameric enzyme and is mainly found in plasma. [2] It is secreted into the blood plasma mainly by the kidneys [1] . Glutathione peroxidase 4 (GPx4) - a monomeric isoenzyme, is of great importance in the metabolism of lipid hydroperoxides; GPx4 is also expressed in almost all mammalian cells at lower levels. It exists in the form of three forms synthesized from the same gene (cytosolic, mitochondrial forms and GPx4 nuclei of sperm cells) [1] . GPx5 is a tetrameric non-selenium GPx specific for the appendages of the testes (formed in the epithelium of the head of the appendage of the testis) [1] . GPx6 is a tetramer, selenoprotein in humans and non-selenium enzyme in rodents, gene expression of this enzyme was detected in mouse embryos and in bowman glands under olfactory epithelium [1] .
Glutathione peroxidase isolated from bovine erythrocytes has a molecular weight of about 84 kDa.
Reaction
An example of a reaction catalyzed by the enzyme glutathione peroxidase is the reaction:
2GSH + H 2 O 2 → GS-SG + 2H 2 O
where GSH is reduced glutathione and GS-SG is glutathione disulfide .
The enzyme glutathione reductase further restores oxidized glutathione and completes the cycle:
GS-SG + NADPH + H + → 2 GSH + NADP + .
Structure
It was found that mammalian GPx1 , GPx2 , GPx3 and GPx4 are selenium-containing enzymes, while GPx6 is human selenoprotein with cysteine-containing homologs in rodents. GPx1, GPx2, and GPx3 are homotetrameric proteins, while GPx4 and GPx7 have a monomeric structure [1] . The integrity of cell and intracellular membranes is highly dependent on glutathione peroxidase . The antioxidant functions of selenium-containing forms of glutathione peroxidase are greatly increased due to the presence of selenium [3] .
Reaction Mechanism
In the active center of the enzyme is the amino acid residue of selenocysteine . The selenium atom is in the oxidation state −1 and is oxidized by hydroperoxide to SeOH. Next, SeOH binds to the glutathione molecule (GSH) to form Se-SG and then binds to another glutathione molecule. In this case, Se is regenerated and a by-product of GS-SG is formed.
Thiol specificity
A strict dependence of the functioning of glutathione peroxidases on GSH is not typical for all isoenzymes of this family. GPx1 is quite strictly specific for GSH, although it can use gamma-glutamylcysteine instead of GSH as a thiol cosubstrate [1] . Evidence has been obtained that GPx3 is able to use reduced homocysteine instead of GSH [4] . GPx3 also reacts well with cysteine, thioredoxin, and glutaredoxin instead of GSH [1] .
Gene Knockouts
Mice knocked out by the glutathione peroxidase Gpx1 gene have a normal phenotype, normal lifespan. These data indicate that this enzyme is not critical for life. However, in mice knocked out by two copies of the gene, cataract prematurely develops and defects in the proliferation of auxiliary muscle cells are observed. [2] However, GPX4 knockout mice of glutathione peroxidase 4 die during early embryonic development. [2] There is evidence that reduced levels of glutathione peroxidase 4 may increase longevity in mice. [five]
There are no data on knockouts of other genes encoding glutathione peroxidase.
Opening
Glutathione peroxidase was discovered in 1957 by Gordon Mills. [6]
Notes
- ↑ 1 2 3 4 5 6 7 8 9 10 Razygraev A.V., Matrosova M.O., Titovich I.A. The role of glutathione peroxidases in endometrial tissue: facts, hypotheses, research prospects // Journal of Obstetrics and Women's Diseases. - 2017. - T. 66 , No. 2 . - S. 104-111 .
- ↑ 1 2 3 Muller FL, Lustgarten MS, Jang Y., Richardson A., Van Remmen H. Trends in oxidative aging theories (English) // Free Radical Biology and Medicine : journal. - 2007 .-- August ( vol. 43 , no. 4 ). - P. 477-503 . - DOI : 10.1016 / j.freeradbiomed.2007.03.03.034 . - PMID 17640558 .
- ↑ Regina Brigelius-Flohé, Leopold Flohé. Selenoproteins of the Glutathione Peroxidase Family (English) // Selenium. - Springer, New York, NY, 2011 .-- P. 167-180 . - ISBN 9781461410249 , 9781461410256. - DOI : 10.1007 / 978-1-4614-1025-6_13 .
- ↑ Razygraev A.V., Taborskaya K.I., Petrosyan M.A., Tumasova Zh.N. Thiol peroxidase activity of rat blood plasma, determined using hydrogen peroxide and 5.5`-dithiobis (2-nitrobenzoic acid) // Biomedical Chemistry. - 2016. - T. 62 , No. 4 . - S. 431-438 . - ISSN 10.18097 / PBMC20166204431 .
- ↑ Ran Q., Liang H., Ikeno Y., et al. Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis (English) // The Journals of Gerontology : journal. - 2007. - Vol. 62 , no. 9 . - P. 932–942 . - PMID 17895430 .
- ↑ MILLS GC Hemoglobin catabolism. I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown (English) // Journal of Biological Chemistry : journal. - 1957. - November ( vol. 229 , no. 1 ). - P. 189-197 . - PMID 13491573 .
See also
- Glutathione reductase
- Selenium