Enzymes hydroxylating

Identification, isolation, and removal of (polyhydroxy)benzenes from the environment have received increased attention throughout the 1980s and 1990s. The biochemical activity of the benzenepolyols is at least in part based on thek oxidation—reduction potential. Many biochemical studies of these compounds have been made, eg, of enzymic glycoside formation, enzymic hydroxylation and oxidation, biological interactions with biochemically important compounds such as the catecholamines, and humic acid formation. The range of biochemical function of these compounds and thek derivatives is not yet fully understood. 

Neural cells convert tyrosine to epinephrine and norepinephrine (Figure 31—5). While dopa is also an intermediate in the formation of melanin, different enzymes hydroxylate tyrosine in melanocytes. Dopa decarboxylase, a pyridoxai phosphate-dependent enzyme, forms dopamine. Subsequent hydroxylation by dopamine P-oxidase then forms norepinephrine. In the adrenal medulla, phenylethanolamine-A -methyltransferase uti-hzes S-adenosyhnethionine to methylate the primary amine of norepinephrine, forming epinephrine (Figure 31-5). Tyrosine is also a precursor of triiodothyronine and thyroxine (Chapter 42). 

Different monooxygenase enzymes hydroxylate the 3 position of the P- and s-rings of a-carotene. Hydroxylation of one ring of P-carotene produces P-cryp-toxanthin and hydroxylation of both P-rings produces zeaxanthin. Hydroxlyation... 

The first test case was the ferrous high-spin state (Fe, S = 2) in the picket-fence porphyrin acetate complex [Fe(CH3COO)(TPpivP)] [13, 23], which is a model for the prosthetic group termed P460 of the multiheme enzyme hydroxyl-amine oxidoreductase from the bacterium Nitrosomonas europeae. Both the picket-fence porphyrin and the protein P460 exhibit an extraordinarily large quadrupole splitting, as observed by conventional Mossbauer studies [56]. 

Different metal species vary in their biological reactivity.98 99 For example, the free ionic form of a metal may act by substituting a cofactor for a vital enzyme. Hydroxylated metal ions have been suggested to bind to the cell surface and alter the net charge of the cell to reduce its viability.101 Because different species may have different effects on biological processes, some species may be more toxic than others. There is a paucity of information in the literature regarding the relative toxicity of different metal species. 

Natnre does not actually make a methylenedioxy group using formaldehyde. Instead, it modifies an existing ortAo-hydroxy-methoxy arrangement. Enzymic hydroxylation of the methoxy methyl converts this substitnent into what is identical to a hemiacetal of formaldehyde, and then acetal formation follows in a process analogous to a chemical synthesis. The hydroxylating enzyme involved is a cytochrome P-450 mono-oxygenase (see Box 11.4). 

A group of related bacterial enzymes hydroxylate alkanes,507 toluene,508 phenol,509 and other substrates.5093 Eukaryotic fatty acid desaturases (Fig. 16-20B) belong to the same family.508 Some bacteria use cytochrome P450 or other oxygenase to add an oxygen atom to an alkene to form an epoxide. For example, propylene... 

It was mentioned above that in aromatic hydroxylation an oxidant is required, and the product yields vary considerably with the oxidant used (for the reason why 02 does not serve as a typical one-electron oxidant, see Chap. 8). A typical example is the formation of tyrosines from phenylalanine (Table 3.4). Their yields are especially low in the absence of an oxidant, since dimerization usually dominates over disproportionation in these systems. The determination of the products is usually done by either HPLC or GC/MS after trimethylsilylation, and the proteins have to be hydrolyzed prior to analysis. Attention has been drawn to the fact that in vivo cytochrome P-450 enzymes hydroxylate phenylalanine to p-tyrosine (Bailey et al. 1997). 

The oxidative cyclization of an ortho-hydroxy-methoxy-substituted aromatic system giving a methylenedioxy group is also known to involve a cytochrome P-450-dependent mono-oxygenase. This enzyme hydroxylates the methyl to yield a formaldehyde hemiacetal intermediate, which can cyclize to the methylenedioxy bridge (the acetal of formaldehyde) by an ionic mechanism (Figure 2.21). 

We have demonstrated recently that epoxidation and hydroxyl-ation can be achieved with simple iron-porphine catalysts with iodosylbenzene as the oxidant (24). Cyclohexene can be oxidized with iodosylbenzene in the presence of catalytic amounts of Fe(III)TPP-Cl to give cyclohexene oxide and cyclohexenol in 55% and 15% yields, respectively. Likewise, cyclohexane is converted to cyclohexanol under these conditions. Significantly, the alcohols were not oxidized rapidly to ketones under these conditions, a selectivity shared with the enzymic hydroxylations. The distribution of products observed here, particularly the preponderance of epoxide and the lack of ketones, is distinctly different from that observed in an autoxidation reaction or in typical reactions of reagents such as chromates or permanganates (15). 

P Oxidation focuses on the ft carbon of the fatty acid. In some instances, it is impossible to form a ketone on the P carbon, for example, if the P carbon is methylated. In such cases, the a carbon may be oxidized to initiate the oxidation process, a Oxidation is useful in the degradation of certain plant materials, such as phytol. The degradation of this compound is illustrated in Figure 19.9. In Refsum disease, caused by a genetic lesion, the enzyme hydroxylating phytanic acid is absent and phytanic acid accumulates in tissues. 

Powerful enzyme hydroxylation systems of organic substrates, i.e. steroids, hydrocarbons, organic acids, alcohols and amines, are operatives in animal and plant tissues and bacteria (Coon et al., 1981 Guengerich and Mcdonald (1984) Weiner, 1986 Sono et al., 1996 Oriz de Montellano, 1995 Sono et al., 1996 Newcomb et al., 2000 Ogliaro et al., 2000, 2001 and references therein). These enzymes catalyze oxidation processes according to the following general scheme ... 

Shapiro, S. and Caspi, E. 1998. The steric course of enzymic hydroxylation at primary carbon atoms. Tetrahedron, 54 5005 0. 

Cytochromes P450 that decorate cores with oxygen-based functionality are commonly found in biosynthetic pathways. For example, these enzymes hydroxylate the reduced polycyclic scaffold of the diterpene taxol and install functional groups that are required for target binding and increase its hydrophilic-ity (31). 

Constituent in active center of many enzymes hydroxyl group can be phosphorylated... 

A similar copper-dependent hydroxylase constitutes the N-terminal domain of the peptidylglycine a-amidating enzyme (Eq. 10-11). This bifunctional enzyme hydroxylates C-terminal glycines in a group of neuropeptide hormones and other secreted peptides. The second functional domain of the enzyme cleaves the hydroxylated glycine to form a C-terminal... 

Salmeterol is highly plasma protein-bound (up to 98 percent). It is metabolized by hepatic microsomal enzymes hydroxylated and excreted through the bile. 

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