Page last updated: 2024-10-24

thioredoxin-disulfide reductase (NADPH) activity

Definition

Target type: molecularfunction

Catalysis of the reaction: thioredoxin-dithiol + NADP+ = thioredoxin-disulfide + H+ + NADPH. [RHEA:20345]

Thioredoxin-disulfide reductase (NADPH) activity is a critical enzymatic function involved in the reduction of disulfide bonds within proteins, specifically targeting thioredoxin (Trx). This process is essential for regulating cellular redox homeostasis and is driven by the enzyme's ability to utilize NADPH as a reducing agent.

The mechanism involves two key steps:

1. **Electron Transfer from NADPH:** NADPH binds to the enzyme and donates an electron to a FAD cofactor within the reductase, reducing it to FADH2.
2. **Disulfide Reduction:** The reduced FADH2 then transfers electrons to the active site cysteine residues of the enzyme, creating a disulfide bond. This reduced form of the enzyme can then interact with oxidized Trx, transferring electrons to reduce the disulfide bond within Trx.

This reduced form of Trx then functions as a reducing agent for various target proteins, influencing a multitude of cellular processes including:

* **DNA replication and repair:** Trx reduces the disulfide bonds of ribonucleotide reductase, an enzyme involved in DNA synthesis.
* **Transcriptional regulation:** Trx regulates the activity of transcription factors like NF-κB by reducing their disulfide bonds.
* **Signal transduction:** Trx participates in various signaling pathways by modulating the activity of signaling proteins through disulfide bond reduction.
* **Protein folding and stability:** Trx assists in the proper folding and stability of proteins by reducing disulfide bonds and preventing aggregation.
* **Defense against oxidative stress:** Trx plays a crucial role in protecting cells against oxidative damage by reducing reactive oxygen species (ROS).

Overall, thioredoxin-disulfide reductase (NADPH) activity is essential for maintaining cellular redox balance, regulating a wide range of cellular processes, and protecting cells from oxidative stress.'
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Proteins (5)

ProteinDefinitionTaxonomy
ThioredoxinA thioredoxin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P10599]Homo sapiens (human)
Thioredoxin reductase 2, mitochondrialA thioredoxin reductase 2, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NNW7]Homo sapiens (human)
Thioredoxin reductase 3A thioredoxin reductase 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q86VQ6]Homo sapiens (human)
Thioredoxin reductase 1, cytoplasmicA thioredoxin reductase 1, cytoplasmic that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16881]Homo sapiens (human)
ThioredoxinA thioredoxin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P10599]Homo sapiens (human)

Compounds (17)

CompoundDefinitionClassesRoles
methylene bluemethylene blue : An organic chloride salt having 3,7-bis(dimethylamino)phenothiazin-5-ium as the counterion. A commonly used dye that also exhibits antioxidant, antimalarial, antidepressant and cardioprotective properties.

Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN.
organic chloride saltacid-base indicator;
antidepressant;
antimalarial;
antimicrobial agent;
antioxidant;
cardioprotective agent;
EC 1.4.3.4 (monoamine oxidase) inhibitor;
EC 3.1.1.8 (cholinesterase) inhibitor;
EC 4.6.1.2 (guanylate cyclase) inhibitor;
fluorochrome;
histological dye;
neuroprotective agent;
physical tracer
3,5-dinitro-4-chloro-alpha,alpha,alpha-trifluorotoluene3,5-dinitro-4-chloro-alpha,alpha,alpha-trifluorotoluene: affects mitochondria isolated from rat liver; RN given refers to unlabeled cpd
naphthazarinnaphthazarin : A naphthoquinone that is 1,4-naphthoquinone in which the hydrogens at positions 5 and 8 are replaced by hydroxy groups.

naphthazarin: fish toxin; isolated for first time from the walnut onigurmi, Juglans mandshurica maxim var. Sieboldiana Makino; structure
hydroxy-1,4-naphthoquinoneacaricide;
antibacterial agent;
antineoplastic agent;
apoptosis inducer;
geroprotector;
plant metabolite
2,6-dichloroindophenol2,6-dichloroindophenol : A quinone imine that is indophenol substituted by chloro groups at positions 2 and 6.

2,6-Dichloroindophenol: A dye used as a reagent in the determination of vitamin C.

N-3,5-dichloro-4-hydroxyphenyl-1,4-benzoquinone imine : 1,4-benzoquinone imine having a 3,5-dichloro-4-hydroxyphenyl substituent attached to the nitrogen atom.
dichlorobenzene;
quinone imine
4-aminophenylarsenoxide4-aminophenylarsenoxide: RN given refers to parent cpd
tetramethylpyrazinetetramethylpyrazine : A member of the class of pyrazines that is pyrazine in which all four hydrogens have been replaced by methyl groups. An alkaloid extracted from Chuanxiong (Ligusticum wallichii).

tetramethylpyrazine: found in Ligusticum chuanxiong
alkaloid;
pyrazines
antineoplastic agent;
apoptosis inhibitor;
bacterial metabolite;
neuroprotective agent;
platelet aggregation inhibitor;
vasodilator agent
staurosporineindolocarbazole alkaloid;
organic heterooctacyclic compound
apoptosis inducer;
bacterial metabolite;
EC 2.7.11.13 (protein kinase C) inhibitor;
geroprotector
palmarumycin cp(1)palmarumycin CP(1): a type of spirobisnaphthalene, which contain two naphthalene-derived c10 units bridged through a spiroketal linkage with two oxygen bridges; structure in first source
1-methylpropyl-2-imidazolyl disulfide1-methylpropyl-2-imidazolyl disulfide: a thioredoxin inhibitor with antineoplastic activityimidazoles
methylnaphthazarinmethylnaphthazarin: structure in first source
piplartinepiplartine: Antineoplastic Agent, Phytogenic; alkaloid from Piper; structure in first sourcecinnamamides;
dicarboximide
xanthohumolxanthohumol : A member of the class of chalcones that is trans-chalcone substituted by hydroxy groups at positions 4, 2' and 4', a methoxy group at position 6' and a prenyl group at position 3'. Isolated from Humulus lupulus, it induces apoptosis in human malignant glioblastoma cells.

xanthohumol: from hop plant, Humulus lupulus
aromatic ether;
chalcones;
polyphenol
anti-HIV-1 agent;
antineoplastic agent;
antiviral agent;
apoptosis inducer;
EC 2.3.1.20 (diacylglycerol O-acyltransferase) inhibitor;
metabolite
curcumincurcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa.

Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.
aromatic ether;
beta-diketone;
diarylheptanoid;
enone;
polyphenol
anti-inflammatory agent;
antifungal agent;
antineoplastic agent;
biological pigment;
contraceptive drug;
dye;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
EC 1.1.1.21 (aldehyde reductase) inhibitor;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor;
EC 1.8.1.9 (thioredoxin reductase) inhibitor;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
flavouring agent;
food colouring;
geroprotector;
hepatoprotective agent;
immunomodulator;
iron chelator;
ligand;
lipoxygenase inhibitor;
metabolite;
neuroprotective agent;
nutraceutical;
radical scavenger
ellagic acidcatechols;
cyclic ketone;
lactone;
organic heterotetracyclic compound;
polyphenol
antioxidant;
EC 1.14.18.1 (tyrosinase) inhibitor;
EC 2.3.1.5 (arylamine N-acetyltransferase) inhibitor;
EC 2.4.1.1 (glycogen phosphorylase) inhibitor;
EC 2.5.1.18 (glutathione transferase) inhibitor;
EC 2.7.1.127 (inositol-trisphosphate 3-kinase) inhibitor;
EC 2.7.1.151 (inositol-polyphosphate multikinase) inhibitor;
EC 2.7.4.6 (nucleoside-diphosphate kinase) inhibitor;
EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
food additive;
fungal metabolite;
geroprotector;
plant metabolite;
skin lightening agent
gambogic acidgambogic acid: RN given refers to (1R-(1alpha,1(Z),3abeta,5alpha,11beta,14aS*))-isomerpyranoxanthonesmetabolite
(1,2-bis(1,2-benzisoselenazolone-3(2h)-ketone))ethane(1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone))ethane: has antineoplastic activity; structure in first source
flavellagic acidflavellagic acid: RN given refers to parent cpd; structure