NADPH-dependent flavin monooxygenase

KMO is a NADPH-dependant flavin monooxygenase which is localized to the outer membrane of mitochondria [66]. KMO is expressed at high levels in the liver, endothelial cells, and monocytic cells and to a lower extent in the brain. Here, its expression is mainly found in cells of glial nature, specifically in microglial cells and in infiltrating macrophages, whereas little or no expression has been found in astrocytes or in neurons [12, 67]. However, the lack of good antibodies to detect... 

Pyridine nucleotide-dependent flavoenzyme catalyzed reactions are known for the external monooxygenase and the disulfide oxidoreductases However, no evidence for the direct participation of the flavin semiquinone as an intermediate in catalysis has been found in these systems. In contrast, flavin semiquinones are necessary intermediates in those pyridine nucleotide-dependent enzymes in which electron transfer from the flavin involves an obligate 1-electron acceptor such as a heme or an iron-sulfur center. Examples of such enzymes include NADPH-cytochrome P4S0 reductase, NADH-cytochrome bs reductase, ferredoxin — NADP reductase, adrenodoxin reductase as well as more complex enzymes such as the mitochondrial NADH dehydrogenase and xanthine dehydrogenase. 

Tertiary amines such as trimethylamine and dimethylamine had long been known to be metabolized to A -oxides by a microsomal amine oxidase that was not dependent on CYP. This enzyme, now known as the microsomal flavin-containing monooxygenase (FMO), is also dependent on NADPH and 02, and has been purified to homogeneity from a number of species. Isolation and characterization of the enzyme from liver and lung samples provided evidence of clearly distinct physicochemical properties and substrate specificities suggesting the presence of at least two different isoforms. Subsequent studies have verified the presence of multiple forms of the enzyme. 

Type I and Type II BVMOs Type I BVMOs consist of only one polypeptide of about 500 amino acids with the cofactor flavin adenine dinucleotide (FAD) tightly bound into the structure, and is dependent on NADPH for activity [60]. Most offlie presently known BVMOs are of this type, and are typically soluble proteins located in the cytosol of bacteria or fungi, which is in contrast to many other monooxygenase systems that often are found to be membrane bound or membrane associated. They contain two Rossmann sequence motifs, GxGxxG, which indicate that these enzymes bind the two cofactors (FAD or NADPH) using separate dinucleotide binding domains [61]. 

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