Hydroxylation of dopamine

Dopamine P-monooxvgenase This enzyme (DBM) catalyzes the hydroxylation of dopamine to the neurotransmitter norepinephrine and is found in a number of higher organisms (17). 

Ascorbic acid or vitamin C is found in fruits, especially citrus fruits, and in fresh vegetables. Man is one of the few mammals unable to manufacture vitamin C in the liver. It is essential for the formation of collagen as it is a cofactor for the conversion of proline and lysine residues to hydroxyproline and hydroxylysine. It is also a cofactor for carnitine synthesis, for the conversion of folic acid to folinic acid and for the hydroxylation of dopamine to form norepinephrine. Being a lactone with two hydroxyl groups which can be oxidized to two keto groups forming dehydroascorbic acid, ascorbic acid is also an anti-oxidant. By reducing ferric iron to the ferrous state in the stomach, ascorbic acid promotes iron absorption. 

A combination of decarboxylation and hydroxyla-tion of the ring of tyrosine produces derivatives of o-dihydroxybenzene (catechol), which play important roles as neurotransmitters and are also precursors to melanin, the black pigment of skin and hair. Catecholamines may be formed by decarboxylation of tyrosine into tyramine (step e, Fig. 25-5) and subsequent oxidation. However, the quantitatively more important route is hydroxylation by the reduced pterin-dependent tyrosine hydroxylase (Chapter 18) to 3,4-dihydroxyphenylalanine, better known as dopa. The latter is decarboxylated to dopamine.1313 Hydroxylation of dopamine by an ascorbic acid and... 

Fig. 4.18 Hydroxylation of dopamine by the non-coupled binuclear copper center in dopamine-/ -monooxygenase.

Dopamine /3-hydroxylase is a monoxygenase that catalyzes the hydroxylation of dopamine to form norepinephrine. This enzyme is localized in the chromaffin granules of the adrenal medulla and in the storage vesicles of central and peripheral catecholaminergic neurons. Since these compounds are unstable, this activity is often assayed by following the formation of octopamine from tyramine. For example, in the assay developed by Feilchenfeld et al. (1982), the reactant tyramine was separated from the product octopamine by reversed-phase, ion-paired HPLC (/uBondapak C18 using a mobile phase of 17% (v/v)... 

The catecholamines (dopamine, norepinephrine, and epinephrine) are derived from dopa in a series of reactions (see Figure 7-12). -Decarboxylation of dopa forms the neurotransmitter dopamine. -Hydroxylation of dopamine on its aliphatic chain by an enzyme that... 

Since the phenylethylamines 312 produced by these decarboxylases are substrates for systems containing dopamine jS-hydroxylase (EC 1.14.17.1), the availability of 7>R and 3S isotopically labeled samples of the aromatic amino acids has allowed the stereochemistry of the hydroxylation of dopamine 313 to yield norepinephrine 314 to be studied (Scheme 83). It was shown that the 3-pro-S hydrogen, Hg, was lost from phenylalanine 297a in the process and that the hydroxylation yielding 314 therefore occurred with retention of configuration (319). 

Dopamine / -monooxygenase (D/3M, EC 1.14.17.1) is an enzyme found in mammalian brains that catalyzes the aerobic hydroxylation of dopamine to norepinephrine (Equation (3))." Ascorbate is the physiological electron donor to the enzyme, so that two equivalents of ascorbate are... 

Also extensively studied are dicopper monooxygenases involved in the regulation of neurotransmitters. Dopamine p-hydroxylase (DpH) catalyzes the stereospecific benzylic hydroxylation of dopamine for the biosynthesis of the hormone norepinephrine, while peptidylglycine a-hydroxylating... 

The catalytic o-hydroxylation of phenols has biological relevance since the working catalyst systems may serve as models for tyrosinase, a copper-containing monooxygenase that effects oxygen insertion into the o-position of tyrosine (46) to produce dopa (47), which is then converted to dopamine (48) by dopa decarboxylase. The hydroxylation of dopamine leads to noradrenaline (49), which is an important neurotransmitter [138-141]. 

Little is known about factors which limit the production of amines. The metabolic reaction which limits the biosynthesis of dopamine and serotonin is believed not to be the decarboxylation of their biochemical precursors dopa and 5-hydroxytryptophane by the ubiquitous decarboxylase, but to be the hydroxylation of the parent compounds tyrosine, and tryptophane. 140-3,189) Under comparable experimental conditions the production of serotonin from 5-hydroxytryptophane took place 30-40 times faster than from tryptophane,and the production of dopamine and noradrenaline respectively from labelled dopa was 70-100 times faster than from labelled tyrosine. In the biosynthesis of noradrenaline, the hydroxylation of dopamine, catalysed by dopamine-j -oxidase, takes place fairly slowly and is considered to be a rate-limiting reaction. ... 

Robertson D, Goldberg MR, Onrot J, Hollister AS, Wiley R, Thompson JGJ, Robertson RM. Isolated failure of autonomic noradrenergic neurotransmission. Evidence for impaired beta-hydroxylation of dopamine. N Engl J Med 1986 314 1494-1497. 

The side-chain hydroxylation of Dopamine is believed to be the rate limiting step in the biosynthesis of the pressor amines (Blaschko, 1956). The reaction had been demonstrated in vitro with the use of adrenal slices (Hagen, 1956) and homogenates (Goodall and Kirschner, 1957) and aqueous extracts of acetone powders (Neri et al., 1956 Kirschner, 1959). In homogenates it was shown (Kirschner, 1959) that the enzymic activity is localized in the particulate fraction obtained by high-speed centrifugation. 

L-Enantiomer of ascorbic acid (AA) is known as vitamin C, the oxidation of AA leads to its conversion into L-dehydroascorbic acid (DHAA). The process is reversible, what is important when AA takes part in oxidation-reduction reactions such as hydroxylation of dopamine to noradrenaline and reduction of folic acid to tetrahydrofolic acid [28]. 

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