Flavin Mixed-Function Oxidases Hydroxylases

The flavin-dependent mixed-function oxidases include amine N-oxidases and a variety of S-oxidases. They provide an alternative to cytochrome P450-dependent enzymes in the metabolism of xenobiotics. 

X-H2 + O2 X-OH + H2O or X + NADPH + O2 X-OH + NADF + H2O Fiavin is reduced by reaction with either substrate-Fi2 or NADPH. 

Fuiiy reduced fiavin-H2 reacts with oxygen to form the fiavin semiquinone radicai and superoxide 

Fiavin semiquinone and superoxide react to form fiavin hydroperoxide fiavin-H + 02 - fiavin-HOOH Fiavin hydroperoxide reacts with substrate 

Cryptochromes in the humtm eye have a considerable sequence emd sti uc-ture homology with the photolyases, bindingboth methylene tetrtihydrofolate and FAD. They have the same DNA binding pocket as photolyase, tdthough they do not catalyze the reduction of DNA pyrimidine dimers. They are found in the nucleus of cells of the inner layer of the retina, behind the rods tmd cones involved in vision (Section 2.3.1), and absorb blue light, with maximum absorbemce at 420 nm. 

Intermediate complex breaks down to hydroxylated product + flavin hydroxide flavin-HOOH-X flavin-OH + X-OH Flavin hydroxide breaks down to regenerate fully oxidized flavin + H2O flavin-OH -s- flavin + H2O 

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The aromatic hydroxylases or mixed-function oxidases are no exception to the above generalization. For maximum activity they require a transition metal ion and an electron donor such as one of the pyridine or flavin nucleotide coenzymes further, they probably utilize molecular oxygen as the source of the hydroxylic oxygen an example is the liver microsomal hydroxylating system (27). As yet there is no comprehensive explanation to cover the mode of action of these enzymes, for on the one hand there are the specific hydroxylases which catalyze such conversions as L-phenylalanine to L-tyrosine (26) or tryptophan to 5-hydroxytrypto-... 

An important group of mixed function oxidases which occur in all types of organism and which are critical in the metabolism of the aromatic amino adds and other aromatic substrates are the aromatic hydroxylases. Their mode of action, the overall stoichiometry of which is represented in the sequence below, results in the introduction of a phenolic hydroxyl group in an aromatic ring system and has been the subject of intensive study. Pyridine and flavin nucleotides, cytochromes, metals (Fe, Cu), ascorbate and pteridine derivatives (H2X) may serve as electron donors. Most, but not all, of these en2yme reactions require transition metal ions for full activity. 

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