Hydroxylases catalyzed

Figure 28-11. The prolyl hydroxylase reaction. The substrate is a proline-rich peptide. During the course of the reaction, molecular oxygen is incorporated into both succinate and proline. Lysyl hydroxylase catalyzes an analogous reaction.

A number of molybdenum-containing hydroxylases catalyzing the first hydrox-ylation step of N-containing compounds have been characterized thoroughly (e.g., carbazole [314], quinoline [327], and indole [350]). The enzyme s redox-active has been described as a molybdenum ion site coordinated to a distinct pyranopterin cofactor (two different [2Fe2S] centers) and in most cases, flavin adenine dinucleotide centers. This active center transfers electrons from the N-heterocyclic substrate to an electron acceptor, which for many molybdenum hydroxylases is still unknown [350],... 

KOCH, B.M., SIBBESEN, O., HALKIER, B.A., SVENDSEN, I., M0LLER, B.L., The primary sequence of cytochrome P450tyr, the multifunctional N-hydroxylase catalyzing the conversion of L-tyrosine to /7-hydroxyphenylacetaldehyde oxime in the biosynthesis of the cyanogenic glucoside dhurrin in Sorghum bicolor (L.) Moench, Arch. Biochem. Biophys., 1995,323, 177-186. 

This enzyme [EC 1.14.15.3], also known as alkane 1-monooxygenase, lauric acid ca-hydroxylase, fatty acid hydroxylate fatty acids in the [Pg.47]

This enzyme [EC 1.14.12.3], also known as benzene hydroxylase, catalyzes the NADH-linked reaction of benzene and dioxygen to produce ds-l,2-dihydrobenzene-... 

Benzoate 1,2-dioxygenase [EC 1.14.12.10], also called benzoate hydroxylase, catalyzes the reaction of benzoate with dioxygen and NADH to generate catechol, carbon dioxide, and NAD+. This is a multiprotein system which contains a reductase which is an iron-sulfur flavoprotein (FAD) and an iron-sulfur oxygenase. 

This enzyme [EC 1.14.13.11], also known as cinnamate 4-hydroxylase, catalyzes the reaction of frans-cinnamate with NADPH and dioxygen to generate 4-hydroxycmna-mate, NADP+, and water. The enzyme, which uses a heme-thiolate as a cofactor, can also replace NADPH with NADH (however, the reaction will proceed slower). 

This enzyme system, also called terminal methyl groups of alkanes and fatty acids. 

This enzyme [EC 1.14.13.2], also known as p-hydroxy-benzoate hydroxylase, catalyzes the reaction of 4-hydroxy-benzoate, NADPH, and dioxygen to produce proto-catechuate, NADP+, and water. FAD is used as a cofactor by this enzyme. The enzyme from Pseudomonas is very specific for the coenzyme substrate whereas 4-hy-droxybenzoate 3-monooxygenase (NAD(P)H) [EC... 

This iron-dependent enzyme [EC 1.14.16.6], also known as L-mandelate 4-hydroxylase, catalyzes the reaction of (5)-2-hydroxy-2-phenylacetate with tetrahydropteridine and dioxygen to produce (5)-4-hydroxymandelate, dihy-dropteridine, and water. 

This enzyme [EC 1.5.1.13], also known as nicotinate hydroxylase, catalyzes the reaction of nicotinate with NADP+ and water to produce 6-hydroxynicotinate and NADPH. This iron-dependent flavoprotein will also oxidize NADPH. 

Peptidylglycine monooxygenase [EC 1.14.17.3], also known as peptidyl a-amidating enzyme and peptidylglycine 2-hydroxylase, catalyzes the reaction of a peptidylglycine with ascorbate and dioxygen to produce a pepti-dyl(2-hydroxyglycine), dehydroascorbate, and water. 

The silatranes studied produce a clear stimulating effect on the formation of oxyproline in intact bones of chick embryos. However, these silatranes do not affect much the activity of collagen propyl-hydroxylase catalyzing the oxyproline formation. 

Dihydroxyphenylalanine (DOPA) (99) is produced by tyrosine hydroxylase-catalyzed hydroxylation of Tyr. Recent interest in the use of [18F]-6-F-DOPA (100) as a PET scanning agent for regional dopaminergic brain function is based on its conversion, in the brain, to [,8F]-6-F-dopamine (101)161. The fact that fluorine in the 6-position of DOPA, dopamine and other catecholamines retards methylation by catechol-O-methyl transferase presumably increases the biological half-life of the tracer. In contrast, fluorine in the 5-position increases the rate of methylation162. 

PAH, a nonheme iron-containing enzyme, is a member of a larger BI Independent amino acid hydroxylase family. In addition to PAH, the enzyme family includes tyrosine hydroxylase and tryptophan hydroxylase. The enzymes in this family participate in critical metabolic steps and are tissue specific. PAH catabolizes excess dietary PA and synthesizes tyrosine. In adrenal and nervous tissue, tyrosine hydroxylase catalyzes the initial steps in the synthesis of dihydrox-yphenylalanine. In the brain, tryptophan is converted to 5-hydroxytryptophan as the first step of serotonin synthesis. Consequently, these enzymes are highly regulated not only by their expression in different tissues but also by reversible phosphorylation of a critical serine residue found in regulatory domains of the three enzymes. Since all three enzymes are phosphorylated and dephosphorylated by different kinases and phosphatases in response to the need for the different synthetic products, it is not unexpected that the exact regulatory signal for each member of the enzyme family is unique. 

Geraniol 10 hydroxylase catalyzes the the cytochrome P450 dependent hydroxylation of geraniol at the C-10 position to commit this substrate to the formation of iridoid monoterpenoids (Fig. 8.2). In Catharanthus roseus, this intermediate is converted to secologanin for producing the tryptamine containing monoterpenoid indole alkaloids characteristic of this plant. 

The catecholamines - dopamine, norepinephrine, and epinephrine are successively derived from tyrosine. S m-thesis occurs in the nerve terminals and in the adrenal gland. Tyrosine hydroxylase catalyzes the first step (Figure 10.2a) and is the major site of regulation (inhibition by dopamine and noradrenaline, activation by cAMP). This step gives rise to 3,4-dihydroxyphenylalanine (L-DOPA), which in turn is a substrate for L-aromatic acid decarboxylase. De-... 

The synthesis of 5-HT from tryptophan in serotonergic neurons occurs in two steps. First, the enzyme tryptophan hydroxylase catalyzes the conversion of tryptophan to 5-hydroxytryptophan (5-HTP). Then, the enzyme aromatic amino acid decarboxylase catalyzes the conversion of 5-FlTP to serotonin. 

Catecholamines are synthesized from the amino acid tyrosine, and serotonin from tryptophan as shown in Figure 29-2. The rate-limiting step in catecholamine biosynthesis involves conversion of tyrosine to 3,4-dihydroxyphenylalanine (L-dopa) by the enzyme, tyrosine hydroxylase. A related enzyme, tryptophan hydroxylase, catalyzes conversion of tryptophan to 5-hydroxytryptophan in the first step of serotonin synthesis. 

A. The enzyme sterol 27-hydroxylase catalyzes the hydroxylation of carbon 27 of the steroid side chain in the conversion of cholesterol to the primary bile acids. It is a mitochondrial, cytochrome P450 enzyme that has a broad specificity and can act on cholesterol as well as its reduced and hydroxylated metabolites. A deficiency in this enzyme leads to decreased bile acid synthesis and increased conversion of cholesterol to cholestanol. 

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