Flavoprotein amine oxidase

From the sequence of reactions found it follows that copper-quinoprotein amine oxidases catalyze an aminotransferase reaction. A different reaction sequence occurs with flavoprotein amine oxidases (EC 1.4.3.4), where formation of NH3 is not dependent on the presence of 02. However, since reductive trapping of amines in the first half-reaction [86] showed attachment of substrate but not of tritium, the mechanism is also different from the aminotransferase reaction that... 

Amine oxidation. As well as the microsomal enzymes involved in the oxidation of amines, there are a number of other amine oxidase enzymes, which have a different subcellular distribution. The most important are the monoamine oxidases and the diamine oxidases. The monoamine oxidases are located in the mitochondria within the cell and are found in the liver and also other organs such as the heart and central nervous system and in vascular tissue. They are a group of flavoprotein enzymes with overlapping substrate specificities. Although primarily of importance in the metabolism of endogenous compounds such as 5-hydroxy try pt-amine, they may be involved in the metabolism of foreign compounds. 

In addition to liver aldehyde dehydrogenase, a number of other enzymes present in the soluble fraction of liver homogenates will oxidize aldehydes and certain N-heterocyclic compounds. Among these are aldehyde oxidase and xanthine oxidase (see below), both flavoprotein enzymes containing molybdenum. These enzymes catalyze the oxidation of aldehydes formed by the deamination of endogenous amines by amine oxidases. 

The secondary amino group in (55) is then oxidized further to give the N-hydroxyl derivative (58), which is converted by a flavoprotein mixed-function amine oxidase into the nitrone derivative (59). Degradation of the nitrone metabolite, followed by oxidation yields 2-ni-troso-l-phenylpropane (60). 

H-Tunneling in Flavoprotein Amine Dehydrogenases Heterotetrameric Sarcosine Oxidase and Engineering Gated Motion in Trimethylamine Dehydrogenase... 

The mechanism by which amines are oxidised by flavoproteins has been an issue of considerable debate in recent years. The debate has been particularly heated in the case of the enzyme monoamine oxidase (Silver-man, 1995). Through the use of a variety of mechanism-based inhibitors and based on studies of nonenzymic mechanisms of amine oxidation, a mechanism for monoamine oxidase in which substrate is initially oxidized by single electron transfer to the enzyme flavin to give an aminium cation... 

Other mono-oxygenases are not cytochrome P450 dependent, such as flavoproteins located in the endoplasmic reticulum that are involved in the oxidation of tertiary amines to N-oxides and of various sulfur compounds. Yet other oxidative enzymes, including alcohol and aldehyde dehydrogenases and monoamine oxidases, are located in the mitochondria or cytosol. 

Monoamine oxidases are flavoproteins that contain one molecule of FAD per molecule. There are two major types of monoamine oxidase (A and B), whose relative concentration varies in tissues of the same species. In general, the A form of the enzyme is more active with endogenous neurotransmitter amines (serotonin, norepinephrine, and epinephrine), whereas the B form is more active toward xenobiotic amines such as 2-phenethylamine. 

Monoamine oxidase is a flavoprotein that catalyzes the oxidative deamination of amines to form the corresponding aldehydes. 02 is the electron acceptor, and NH3 and H202 are the other products. (PNMT = phenylethanolamine-N-methyltransferase.)... 

Monoamine oxidase B (MAO-B) is a membrane-bound flavoprotein that catalyzes the two-electron oxidation of primary, secondary, and tertiary amines with a preference for primary amines. Extensive studies have addressed the issue of whether the hydrogen transfer occurs via a step-wise mechanism (i.e. electron transfer followed by H+) or a concerted process (H ) (e.g. Refs. 103, 104). 

This flavoprotein, which catalyzes the oxidative deamination of amines, functions in the breakdown of endogenously produced neurotransmitter amines. Vertebrate monoamine oxidase also catalyzes the oxidation of xenobiotic amines, particularly in tissues such as the intestine (4). Whether the schistosome enzyme is also capable of metabolizing xenobiotics has not been investigated. 

MAO oxidizes amines, particularly biogenic amines involved as neurotransmitters (Cashman, 1997). Like FMO, this is a flavoprotein oxidase, but the mechanism is different ... 

The formation of N-oxides of tertiary amines and demethylation of secondary amines are biochemical processes which may also be involved in detoxification. In the case of A, iV-dimethylaniline, the N-oxide is considered to be the possible intermediate in its NADPH- and oxygen-dependent oxidative demethylation. The formation of this A -oxide appears to be catalyzed via a flavoprotein oxidase (509). Tertiary amine A -oxides, thus formed, are often excreted in urine. In the case of A -methyl-4-aminoazobenzene (MAB), demethylation to 4-aminoazoben-zene (AB) appears to occur via a cytochrome P-450 mediated oxidation. Since an A -methyl substituent is regarded as essential for carcinogenic activity among derivatives of AB, this oxidative demethylation would be a specific mode of detoxifying this carcinogenic aromatic amine. 

Porcine kidney D-amino acid oxidase (pkDAAOx) was identified as the first mammalian flavoprotein to catalyze the oxidative deamination of a-amino acids with strict i -stereoselectivity. pkDAAOx is widely used as a general reagent in research and bioassays of D-amino acids. Although many studies have been conducted on its purification, characterization, gene cloning, expression, and X-ray crystal structure, pkDAAOx was not shown to catalyze the oxidation of amines or even LAAOx, which belongs to the AOx protein family. 

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