Oxygenases iron-containing

The formation of Hyp and Hyl residues in procollagen is catalyzed by iron-containing oxygenases ( proline and lysine hydroxylase, EC 1.14.11.1/2). Ascorbate is required to maintain their function. Most of the symptoms of the vitamin C deficiency disease scurvy (see p. 368) are explained by disturbed collagen biosynthesis. 

Tryptophan oxygenase is another iron-containing enzyme which, like catalase, is inhibited by pyrazole in vivo but not in vitro. Again, however, the metabolite 4-hydroxypyrazole is active in vitro and shows, in contrast to catalase, competitive inhibition with tryptophan for the enzyme (79MI10505). Adrenaline and other phenols are also inhibitors of this enzyme and in this case, therefore, the heterocyclic ring appears not to be essential for activity. 

In 1989, BH4 was found to be a cofactor for nitric oxide synthase (NOS) [ 126, 127]. BH4 is also involved in dimerization of NOS, as NOS is catalytically active in a homodimer structure. Three isoforms of NOS exist neuronal NOS (NOS 1), inducible NOS (NOS 2) and endothelial NOS (NOS 3). BH4 is essential for all NOS isoforms. The NOS isoforms share approximately 50-60% sequence homology. Each NOS polypeptide is comprised of oxygenase and reductase domains. An N-terminal oxygenase domain contains iron protoporphyrin IX (heme), BH4 and an arginine binding site, and a C-terminal reductase domain contains flavin mononucleotide (FMN), and a reduced nicotin-amide adenine dinucleotide phosphate (NADPH) binding site. 

A recent summary25 of the activation of O2 by cytochrome P-450 (an iron(III)-heme protein with a axial cysteine thiolate ligand) concludes that the reactive form of this mono-oxygenase also contains an oxene-ferryl group (RS)(por)FeV=O. The mono-oxygenase chemistry of cytochrome P-450 has been modeled via the use of (TPP)Fei lCl(TPP=tetraphenylporphyrin) and (OEP)Fe JCl (OEP=octaethylporphyrin) with peracids,26,27 iodosobenzene,26,27... 

Why is vitamin C used so extensively as an electron donor There are two main reasons. First, vitamin C is very soluble in water, so it can be concentrated in confined spaces surrounded by membranes (which are made of lipids impermeable to vitamin C). The synthesis of noradrenaline from dopamine, for example, takes place in small membrane-bounded spaces, or vesicles, within cells of the cortex of the adrenal glands. The vitamin C concentration inside these vesicles reaches about 100 times that of blood plasma. As vitamin C is consumed by the enzyme dopamine mono-oxygenase, electrons are passed across the vesicle membrane (via an iron-containing protein, cytochrome b65l), to regenerate vitamin C within the vesicles. Thus, for periods of days or weeks, the intracellular vitamin C needed for physiological tasks can be insulated from changes in plasma levels caused by variations in diet, and maintained at the ideal levels for a particular reaction. 

XI.2.B. OTHER NONE-HEME IRON-CONTAINING OXYGENASES... 

X1.2.B. Other None-Heme Iron-Containing Oxygenases 481... 

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