Page last updated: 2024-10-24

superoxide-generating NAD(P)H oxidase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: NAD(P)H + O2 = NAD(P)H + O2-. [GOC:ai, PMID:10806195]

Superoxide-generating NAD(P)H oxidase activity is a crucial molecular function that catalyzes the production of superoxide radicals (O2-) from molecular oxygen (O2) using NADH or NADPH as electron donors. This process involves the transfer of electrons from NAD(P)H to molecular oxygen, with the subsequent generation of superoxide. This enzymatic activity is primarily associated with a family of transmembrane enzymes known as NADPH oxidases (NOXs), which are found in various cell types and play critical roles in diverse physiological and pathological processes.

The core catalytic unit of NOXs comprises a flavin adenine dinucleotide (FAD) binding site and a heme-binding site. The electron transfer pathway involves the sequential reduction of FAD and heme by NAD(P)H, followed by the transfer of an electron to molecular oxygen, resulting in the formation of superoxide. This superoxide production is tightly regulated by various factors, including intracellular signaling pathways, protein-protein interactions, and cellular redox status.

Superoxide generated by NAD(P)H oxidases has a wide range of downstream effects, participating in various signaling pathways and contributing to cellular processes such as inflammation, host defense, and wound healing. It also plays a role in various pathologies, including cardiovascular disease, cancer, and neurodegenerative disorders. For example, in immune cells, NOXs contribute to the generation of reactive oxygen species (ROS), which are essential for pathogen killing and inflammation. In vascular smooth muscle cells, NOXs contribute to vasoconstriction and vascular remodeling. Moreover, NOXs are implicated in the pathogenesis of several chronic diseases, such as atherosclerosis and hypertension.

In summary, superoxide-generating NAD(P)H oxidase activity is a critical enzyme function involved in diverse cellular processes by producing superoxide radicals. This activity is tightly regulated and plays essential roles in both physiological and pathological processes, impacting various aspects of cellular signaling, host defense, and disease pathogenesis.'
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Proteins (2)

ProteinDefinitionTaxonomy
NADPH oxidase 4An NADPH oxidase 4 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q9NPH5]Homo sapiens (human)
Neutrophil cytosol factor 1A neutrophil cytosol factor 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P14598]Homo sapiens (human)

Compounds (26)

CompoundDefinitionClassesRoles
1-(1-naphthyl)piperazine1-(1-naphthyl)piperazine: serotonin agonist; structure given in first sourceN-arylpiperazine
ebselenebselen : A benzoselenazole that is 1,2-benzoselenazol-3-one carrying an additional phenyl substituent at position 2. Acts as a mimic of glutathione peroxidase.benzoselenazoleanti-inflammatory drug;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor;
EC 1.3.1.8 [acyl-CoA dehydrogenase (NADP(+))] inhibitor;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor;
EC 2.5.1.7 (UDP-N-acetylglucosamine 1-carboxyvinyltransferase) inhibitor;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
EC 3.1.3.25 (inositol-phosphate phosphatase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 3.5.4.1 (cytosine deaminase) inhibitor;
EC 5.1.3.2 (UDP-glucose 4-epimerase) inhibitor;
enzyme mimic;
ferroptosis inhibitor;
genotoxin;
hepatoprotective agent;
neuroprotective agent;
radical scavenger
2-hydroxy-5-(2,5-dihydrobenzyl)aminobenzoic acidaromatic amine
quipazineQuipazine: A pharmacologic congener of serotonin that contracts smooth muscle and has actions similar to those of tricyclic antidepressants. It has been proposed as an oxytocic.piperazines;
pyridines
carbostyrilquinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.

Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.
monohydroxyquinoline;
quinolone
bacterial xenobiotic metabolite
quinolineazaarene;
mancude organic heterobicyclic parent;
ortho-fused heteroarene;
quinolines
2-naphthylamine2-naphthylamine : A naphthylamine carrying the amino group at position 2.

2-Naphthylamine: A naphthalene derivative with carcinogenic action.
naphthylaminecarcinogenic agent
2-methylquinoline2-methylquinoline: RN given refers to parent cpd

methylquinoline : Any member of the class of quinolines carrying at least one methyl substituent.

quinaldine : A quinoline compound in which the quinoline skeleton is substituted at C-2 with a methyl group.
quinolines
2-aminopyrimidineaminopyrimidine : A member of the class of pyrimidines that is pyrimidine substituted by at least one amino group and its derivatives.

pyrimidin-2-amine : An aminopyrimidine carrying an amino group at position 2.
aminopyrimidine
2-aminobenzothiazolebenzothiazoles
alpha-aminopyridinealpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485

aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups.
8-aminoquinoline
6-aminoquinoline
1,2-Dihydroquinolin-2-imineaminoquinoline
5-aminoquinoline
staurosporineindolocarbazole alkaloid;
organic heterooctacyclic compound
apoptosis inducer;
bacterial metabolite;
EC 2.7.11.13 (protein kinase C) inhibitor;
geroprotector
4-aminoquinoline
1-(4-pyridyl)piperazine1-(4-pyridyl)piperazine: structure in first source
1-aminoisoquinoline
4-amino-2-methylquinoline4-amino-2-methylquinoline: used to induce miniature endplate potentials
quercetin7-hydroxyflavonol;
pentahydroxyflavone
antibacterial agent;
antineoplastic agent;
antioxidant;
Aurora kinase inhibitor;
chelator;
EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor;
geroprotector;
phytoestrogen;
plant metabolite;
protein kinase inhibitor;
radical scavenger
3,7-dimethoxy-5,3',4'-trihydroxyflavone3,7-dimethoxy-5,3',4'-trihydroxyflavone: isolated from Veronia eremophila; structure given in first source

3',4',5-trihydroxy-3,7-dimethoxyflavone : A dimethoxyflavone that the 3,7-di-O-methyl derivative of quercetin.
dimethoxyflavone;
trihydroxyflavone
EC 1.3.1.22 [3-oxo-5alpha-steroid 4-dehydrogenase (NADP(+))] inhibitor;
metabolite
apigeninChamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia.trihydroxyflavoneantineoplastic agent;
metabolite
luteolin3'-hydroxyflavonoid;
tetrahydroxyflavone
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
c-Jun N-terminal kinase inhibitor;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
immunomodulator;
nephroprotective agent;
plant metabolite;
radical scavenger;
vascular endothelial growth factor receptor antagonist
kaempferol7-hydroxyflavonol;
flavonols;
tetrahydroxyflavone
antibacterial agent;
geroprotector;
human blood serum metabolite;
human urinary metabolite;
human xenobiotic metabolite;
plant metabolite
azaleatinazaleatin : A monomethoxyflavone that is quercetin in which the hydroxy group at position 5 is replaced by a methoxy group.7-hydroxyflavonol;
monomethoxyflavone;
tetrahydroxyflavone
plant metabolite