NADPH oxidases (NOXs) are the membrane-binding enzyme complexes found in the membrane of intracellular organelles. It is known as a primary source of ROS. NOXs can catalyze electron donor NADPH or NADH and transfer electrons to molecular oxygen leading to superoxide anion production. The electron transfer system in NOX is composed of the C-terminal cytoplasmic region, and the N-terminal six-transmembrane domains containing two hemes, a structure similar to that of cytochrome b of the mitochondrial bc1 complex. NOXs are responsible for killing the intracellular pathogens through promoting the production of superoxide in phagocytic cells. Besides, NOXs present in the vascular wall is associated with vascular diseases such as Ang II-induced hypertension, diabetes mellitus, and atherosclerosis. It is reported that ROS produced by NOXs can activate an enzyme that promotes the macrophages containing cholesterol adhere to the artery wall leading to atherosclerosis. While NOX inhibitors can reverse atherosclerosis.
NOX contains several isoforms including NOX1-5, NOX oxidase 1 and 2, NOX organizer 1, and NOX activator 1. Here is part of NOXs in humans including NOX1, NOX4, and NOX5. NOX4 is most associated with idiopathic pulmonary fibrosis (IPF) and highly expressed in pulmonary fibroblasts of patients with IPF. NOX5 is not only as an electron transferring enzyme but also a calcium-dependent proton channel.
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