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Oxygen dependent killing is done through:
NADPH oxidase.
Superoxide dismutase.
Catalase.
Glutathione reductase.
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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.
Under normal circumstances, the complex is 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 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).
Role in pathology
NADPH oxidase is a major cause of atherosclerosis, and NADPH oxidase inhibitors may reverse atherosclerosis. Atherosclerosis is caused by the accumulation of macrophages containing cholesterol (foam cells) in artery walls (in the intima). NADPH oxidase produces ROSs. These ROSs activate an enzyme that makes the macrophages adhere to the artery wall (by polymerizing actin fibers). This process is counterbalanced by NADPH oxidase inhibitors, and by antioxidants. An imbalance in favor of ROS produces atherosclerosis. In vitro studies have found that the NADPH oxidase inhibitors apocynin and diphenyleneiodonium, along with the antioxidants N-acetyl-cystine and resveratrol, depolymerized the actin, broke the adhesions, and allowed foam cells to migrate out of the intima.
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 autosomal recessive cytochrome b-positive CGD type II.
1.NADPH oxidase
ReplyDeleteThe 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.
Under normal circumstances, the complex is 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 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).
Role in pathology
NADPH oxidase is a major cause of atherosclerosis, and NADPH oxidase inhibitors may reverse atherosclerosis. Atherosclerosis is caused by the accumulation of macrophages containing cholesterol (foam cells) in artery walls (in the intima). NADPH oxidase produces ROSs. These ROSs activate an enzyme that makes the macrophages adhere to the artery wall (by polymerizing actin fibers). This process is counterbalanced by NADPH oxidase inhibitors, and by antioxidants. An imbalance in favor of ROS produces atherosclerosis. In vitro studies have found that the NADPH oxidase inhibitors apocynin and diphenyleneiodonium, along with the antioxidants N-acetyl-cystine and resveratrol, depolymerized the actin, broke the adhesions, and allowed foam cells to migrate out of the intima.
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
autosomal recessive cytochrome b-positive CGD type II.