NADPH oxidase
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The NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) is a membrane-bound enzyme complex. It can be found in the plasma membrane as well as in the membrane of phagosome.
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[edit] Subunits
It is made up of six subunits. These subunits are:
- a Rho guanosine triphosphatase (GTPase), usually Rac1 or Rac2 (Rac stands for Rho-related C3 botulinum toxin substrate)
- Five "phox" units. (Phox stands for phagocytic oxidase.)
- P91-PHOX (contains heme)
- p22phox
- p40phox
- p47phox
- p67phox
[edit] Function
The complex is normally latent in neutrophils and is activated to assemble in the membranes during respiratory burst.
It generates superoxide by transferring electrons from NADPH inside the cell across the membrane and coupling these to molecular oxygen to produce the superoxide, which is a highly-reactive free-radical. Superoxide can be produced in phagosomes, which contain ingested bacteria and fungi, or it can be produced outside of the cell. In a phagosome, superoxide can spontaneously form hydrogen peroxide that will undergo further reactions to generate reactive oxygen species (ROS).
Superoxide and other ROS are capable of killing bacteria and fungi by its ability to react with other body compounds to generate a large family of reactive oxygen species. These include hydrogen peroxide and hypochlorous acid, the reactive agent in bleach.
[edit] Role in pathology
Mutations in the NADPH oxidase subunit genes cause several Chronic Granulomatous Diseases (CGD), such as
- X-linked chronic granulomatous disease (CGD),
- autosomal recessive cytochrome b-negative CGD,
- autosomal recessive cytochrome b-positive CGD type I and
- autosomal recessive cytochrome b-positive CGD type II.
In this disease cells have a low capacity for phagocytosis and persistent bacterial infections occur. Areas of infected cells are common, granulomas. A similar disorder called neutrophil immunodeficiency syndrome is linked to a mutation in the RAC2, also a part of the complex.
One study suggests a role for NADPH oxidase in ketamine-induced loss of neuronal parvalbumin and GAD67 expression.[1] Similar loss is observed in schizophrenia, and the results may point at the NADPH oxidase as a possible player in the pathophysiology of the disease.[2]
[edit] Chemical reaction
- NADPH + 2O2 ↔ NADP+ + 2O2°- + H+
[edit] Inhibition
NADPH oxidase can be inhibited by apocynin and DPI.Apocynin prevents the assembly of its subunits.
[edit] References
- ^ Behrens MM, Ali SS, Dao DN, Lucero J, Shekhtman G, Quick KL, Dugan LL (2007). "Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase". Science 318 (5856): 1645–7. doi:. PMID 18063801.
- ^ Tom Fagan. Does Oxidative Stress Link NMDA and GABA Hypotheses of Schizophrenia? Schizophrenia Research Forum. December 09, 2007. Available at http://www.schizophreniaforum.org/new/detail.asp?id=1413. Accessed December 11, 2007.
[edit] External links
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