Target type: molecularfunction
Catalysis of the reaction: [thioredoxin]-dithiol + hydrogen peroxide = [thioredoxin]-disulfide + H2O. [RHEA:63528]
Thioredoxin peroxidase activity is a critical enzymatic function involved in the detoxification of reactive oxygen species (ROS) and the maintenance of cellular redox homeostasis. Thioredoxin peroxidases (TPXs) are a family of selenocysteine-containing enzymes that catalyze the reduction of hydrogen peroxide (H2O2) and organic hydroperoxides to water and alcohols, respectively, using thioredoxin (Trx) as an electron donor. This reduction process involves the transfer of electrons from Trx, which is in its reduced form, to the active site of TPX, where it reduces the hydroperoxide. The oxidized form of Trx is then recycled by thioredoxin reductase, which uses NADPH as an electron source.
The molecular function of TPX activity can be broken down into the following steps:
1. **Substrate Binding:** The TPX enzyme binds to its substrate, such as H2O2 or an organic hydroperoxide, at the active site.
2. **Selenocysteine Oxidation:** The selenocysteine residue at the active site of TPX is oxidized by the hydroperoxide substrate, forming a selenenic acid intermediate.
3. **Trx Reduction:** The reduced form of Trx binds to the TPX enzyme and donates an electron to the selenenic acid intermediate, reducing it back to the selenol form.
4. **Product Release:** The reduced hydroperoxide (water or alcohol) is released from the active site of TPX, and the oxidized form of Trx is released.
5. **Trx Regeneration:** The oxidized Trx is recycled by thioredoxin reductase, which uses NADPH as an electron source.
The overall reaction catalyzed by TPX can be summarized as follows:
H2O2 + 2 Trx(reduced) + NADPH + H+ → 2 H2O + 2 Trx(oxidized) + NADP+
Thioredoxin peroxidase activity is essential for cellular protection against oxidative stress. Oxidative stress, caused by an imbalance between the production and detoxification of ROS, can lead to damage to proteins, lipids, and DNA, contributing to various diseases. TPX activity helps to prevent oxidative damage by detoxifying ROS and maintaining cellular redox homeostasis, thereby promoting cellular survival and protecting against disease.'
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Protein | Definition | Taxonomy |
---|---|---|
Peroxiredoxin-1 | A peroxiredoxin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q06830] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
piericidin a | piericidin A : A member of the class of monohydroxypyridines that acts as an irreversible mitochondrial Complex I inhibitor that strongly associates with ubiquinone binding sites in both mitochondrial and bacterial forms of NADH:ubiquinone oxidoreductase piericidin A: pyridine-substituted fatty alcohol antibiotic; minor descriptor (75-85); on-line & Index Medicus search ANTIBIOTICS (75-85); RN given refers to (S-(R*,R*-(all-E)))-isomer | aromatic ether; methylpyridines; monohydroxypyridine; secondary allylic alcohol | antimicrobial agent; bacterial metabolite; EC 1.6.5.3 [NADH:ubiquinone reductase (H(+)-translocating)] inhibitor; mitochondrial respiratory-chain inhibitor |
glucopiericidin a | glucopiericidin A: from Streptomyces pactum S48727 as co-metabolite of piericidin A(1); structure given in first source; glycoside antibiotic |