Flavin monooxygenases amines

Major oxidations are aromatic, aliphatic, alicyclic, heterocyclic, N-oxidation, S-oxidation, dealkylation. Other enzymes also catalyze phase 1 reactions microsomal flavin monooxygenases, amine oxidases, peroxidases, and alcohol 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. 

In addition to cytochrome P-450 enzymes, another enzyme that mediates phase I oxidations is flavin-containing monooxygenase (FMO), likewise contained in the endoplasmic reticulum. It is especially effective in oxidizing primary, secondary, and tertiary amines. Additionally, it catalyzes oxidation of other nitrogen-containing xenobiotic compounds, as well as those that contain sulfur and phosphorus, but does not bring about hydroxylation of carbon atoms. 

Enzymatic hydroxylation of a carbon adjacent to an oxygen or nitrogen usually results in dealkylation by spontaneous hydrolysis of the initial hemiacetal or hemiaminal product. These conversions are commonly employed for two synthetic purposes cleavage of methyl ethers and oxidative deamination of amines. The latter is particularly useful in amino-add chemistry. These reactions can be catalyzed by P-450 monooxygenases or by flavin-containing monooxygenases (which are typically metal-free enzymes). As in the previous example, these hydroxylations require two dectrons that must be supplied by NADH or NAD PH, and most synthetic applications have rdied on whole miaobial cells rather than the isolated enzymes (Figure 1.7). 

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