Catecholamines reactions

Amino acid-derived hormones include the catecholamines, epinephrine and norepinephrine (qv), and the thyroid hormones, thyroxine and triiodothyronine (see Thyroid AND ANTITHYROID PREPARATIONS). Catecholamines are synthesized from the amino acid tyrosine by a series of enzymatic reactions that include hydroxylations, decarboxylations, and methylations. Thyroid hormones also are derived from tyrosine iodination of the tyrosine residues on a large protein backbone results in the production of active hormone. 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Note The pre- and post-treatment of the chromatograms with the basic tri-ethylamine solution, which can be replaced by an alcoholic solution of sodium hydroxide [1,4] or a phosphate buffer solution pH = 8.0 (c = 0.2 mol/1) [5], serves to stabilize the fluorescence of the amino derivatives [2]. A final spraying with methanolic hydrochloric acid (chci = 5 mol/1) or 70% perchloric acid renders the detection reaction highly specific for histamine [4] and for catecholamines and indolamines [5]. 

The next two examples illustrate more complex surface reaction chemistry that brings about the covalent immobilization of bioactive species such as enzymes and catecholamines. Poly [bis (phenoxy)-phosphazene] (compound 1 ) can be used to coat particles of porous alumina with a high-surface-area film of the polymer (23). A scanning electron micrograph of the surface of a coated particle is shown in Fig. 3. The polymer surface is then nitrated and the arylnitro groups reduced to arylamino units. These then provided reactive sites for the immobilization of enzymes, as shown in Scheme III. 

The pathway for synthesis of the catecholamines dopamine, noradrenaline and adrenaline, illustrated in Fig. 8.5, was first proposed by Hermann Blaschko in 1939 but was not confirmed until 30 years later. The amino acid /-tyrosine is the primary substrate for this pathway and its hydroxylation, by tyrosine hydroxylase (TH), to /-dihydroxyphenylalanine (/-DOPA) is followed by decarboxylation to form dopamine. These two steps take place in the cytoplasm of catecholaminereleasing neurons. Dopamine is then transported into the storage vesicles where the vesicle-bound enzyme, dopamine-p-hydroxylase (DpH), converts it to noradrenaline (see also Fig. 8.4). It is possible that /-phenylalanine can act as an alternative substrate for the pathway, being converted first to m-tyrosine and then to /-DOPA. TH can bring about both these reactions but the extent to which this happens in vivo is uncertain. In all catecholamine-releasing neurons, transmitter synthesis in the terminals greatly exceeds that in the cell bodies or axons and so it can be inferred... 

Because LCEC had its initial impact in neurochemical analysis, it is not, surprising that many of the early enzyme-linked electrochemical methods are of neurologically important enzymes. Many of the enzymes involved in catecholamine metabolism have been determined by electrochemical means. Phenylalanine hydroxylase activity has been determined by el trochemicaUy monitoring the conversion of tetrahydro-biopterin to dihydrobiopterin Another monooxygenase, tyrosine hydroxylase, has been determined by detecting the DOPA produced by the enzymatic reaction Formation of DOPA has also been monitored electrochemically to determine the activity of L-aromatic amino acid decarboxylase Other enzymes involved in catecholamine metabolism which have been determined electrochemically include dopamine-p-hydroxylase phenylethanolamine-N-methyltransferase and catechol-O-methyltransferase . Electrochemical detection of DOPA has also been used to determine the activity of y-glutamyltranspeptidase The cytochrome P-450 enzyme system has been studied by observing the conversion of benzene to phenol and subsequently to hydroquinone and catechol... 

The most commonplace substrates in energy-transfer analytical CL methods are aryl oxalates such as to(2,4,6-trichlorophenyl) oxalate (TCPO) and z s(2,4-dinitrophenyl) oxalate (DNPO), which are oxidized with hydrogen peroxide [7, 8], In this process, which is known as the peroxyoxalate-CL (PO-CL) reaction, the fluorophore analyte is a native or derivatized fluorescent organic substance such as a polynuclear aromatic hydrocarbon, dansylamino acid, carboxylic acid, phenothiazine, or catecholamines, for example. The mechanism of the reaction between aryl oxalates and hydrogen peroxide is believed to generate dioxetane-l,2-dione, which may itself decompose to yield an excited-state species. Its interaction with a suitable fluorophore results in energy transfer to the fluorophore, and the subsequent emission can be exploited to develop analytical CL-based determinations. 

The CL enhancement of the lucigenin reaction with catecholamines in the presence of HTAH micelles was used for determination of dopamine, norepinephrine, and epinephrine [42], However, the presence of an anionic surfactant, SDS, inhibits the CL of the system. The aforementioned CL enhancement in the presence of HTAH can be explained in the following way the deprotonated forms of the catecholamines are expected to be the principal species present in aqueous alkaline solution due to the dissociation of the catechol hydroxyl groups, and to react with lucigenin to produce CL. The anionic form of the catecholamines and the hydroxide ion interact electrostatically with and bond to the cationic micelle, to which the lucigenin also bonds. Therefore, the effective concentration of the... 

One of the nonionic surfactants most used as an enhancer of chemiluminescent reactions is Brij-35. This surfactant increases the reaction of lucigenin with catecholamines by a factor of 2.6 compared with the CL intensity in an aqueous medium [42], This enhancement can be explained in the following way it is known that oxygen from the polyoxyethylene chains in Brij-35 can react with sodium ion to form an oxonium ion, by which means the polyoxyethylene chains act as an oxonium cation. In this way the increase in CL intensity due to Brij-35 can be attributed to the same effect described for the micelles of a cationic surfactant. 

The effect of non-participating ligands on the copper catalyzed autoxidation of cysteine was studied in the presence of glycylglycine-phosphate and catecholamines, (2-R-)H2C, (epinephrine, R = CH(OH)-CH2-NHCH3 norepinephrine, R = CH(OH)-CH2-NH2 dopamine, R = CH2-CH2-NH2 dopa, R = CH2-CH(COOH)-NH2) by Hanaki and co-workers (68,69). Typically, these reactions followed Michaelis-Menten kinetics and the autoxidation rate displayed a bell-shaped curve as a function of pH. The catecholamines had no kinetic effects under anaerobic conditions, but catalyzed the autoxidation of cysteine in the following order of efficiency epinephrine = norepinephrine > dopamine > dopa. The concentration and pH dependencies of the reaction rate were interpreted by assuming that the redox active species is the [L Cun(RS-)] ternary complex which is formed in a very fast reaction between CunL and cysteine. Thus, the autoxidation occurs at maximum rate when the conditions are optimal for the formation of this species. At relatively low pH, the ternary complex does not form in sufficient concentration. 

Phenylephrine (27) is a low-potency sympathomimetic amine used as a decongestant. Solutions become coloured due to an auto-oxidation accelerated by light. In a series of experiments, aqueous solutions of the hydrochloride were left under a UV lamp until a tan colour developed. HPLC analysis showed four main products of which one was identified as adrenaline (19). Even after prolonged irradiation, there was never more than 2% adrenaline in the solution. It was assumed that the catecholamine was removed as it formed by further reaction to adrenochrome and melanine, which accounted for the colour [34],... 

The first step is catalysed by the tetrahydrobiopterin-dependent enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), which is regulated by end-product feedback is the rate controlling step in this pathway. A second hydroxylation reaction, that of dopamine to noradrenaline (norepinephrine) (dopamine [3 oxygenase) requires ascorbate (vitamin C). The final reaction is the conversion of noradrenaline (norepinephrine) to adrenaline (epinephrine). This is a methylation step catalysed by phenylethanolamine-jV-methyl transferase (PNMT) in which S-adenosylmethionine (SAM) acts as the methyl group donor. Contrast this with catechol-O-methyl transferase (COMT) which takes part in catecholamine degradation (Section 4.6). 

In contrast to glutamate, y-aminobutyric acid (y-aminobutyrate, GABA) is an inhibitory compound. Metabolically derived from glutamate, GABA production illustrates a reaction, decarboxylation, common to the production of serotonin and the catecholamines (Figure 4.9). 

Figure 4.10 Direct analysis of catecholamines in urine sample. Column, Asahipak ES-502C eluent, 75 mM succinic acid + 25 mM borate buffer (pH 6.10) containing 0.5 mM EDTA flow rate, 1.0 min-1 detection, fluorescence reaction detection Ex. 350 nm. Peaks-. 1, adrenaline-, 2, noradrenaline-, and 3, dopamine.

Vitamin C is essential for the formation of collagen, the principal structural protein in skin, bone, tendons, and ligaments, being a cofactor in the hydroxylation of the amino acids proline to 4-hydroxyproline, and of lysine to 5-hydroxylysine. These hydroxyamino acids account for up to 25% of the collagen structure. Vitamin C is also associated with some other hydroxylation reactions, e.g. the hydroxylation of tyrosine to dopa (dihydroxyphenylalanine) in the pathway to catecholamines (see Box 15.3). Deficiency leads to scurvy, a condition characterized by muscular pain, skin lesions, fragile blood vessels, bleeding gums, and tooth loss. Vitamin C also has valuable antioxidant properties (see Box 9.2), and these are exploited commercially in the food industries. 

Several amino acids are broken down by de-carbo qflation. This reaction gives rise to what are known as biogenic amines, which have various functions. Some of them are components of biomolecules, such as ethanolamine in phospholipids (see p. 50). Cysteamine and T-alanine are components of coenzyme A (see p.l2) and of pantetheine (see pp. 108, 168). Other amines function as signaling substances. An important neurotransmitter derived from glutamate is y-aminobutyrate (GABA, see p.356). The transmitter dopamine is also a precursor for the catecholamines epinephrine and norepinephrine (see p.352). The biogenic amine serotonin, a substance that has many effects, is synthesized from tryptophan via the intermediate 5-hydroxytryptophan. 

Norepinephrine is the primary neurotransmitter produced and released by adrenergic neurons, and in literature it is also described as and called (-) noradrenaline or levarterenol. This vasopressor catecholamine reduces both the resistance and capacity of blood vessels by stimulating a-adrenoreceptors and having a direct cardiostimulatory effect, which is accomplished by activation of )3i-adrenoreceptors. Norepinephrine exhibits significantly less activity than epinephrine as a drug for widening blood vessels through the activation of jSj-adrenoreceptors. Elevation of both stylistic and diastolic blood pressure is a typical reaction to intravenous introduction of norepinephrine. 

Drug/Lab test interactions A labetalol metabolite may falsely increase urinary catecholamine levels when measured by a nonspecific trihydroxyindole reaction. Drug/Food interactions Food may increase bioavailability of the drug. 

When stimulation of Gl motility might be dangerous (eg, in the presence of Gl hemorrhage, mechanical obstruction, or perforation) pheochromocytoma (the drug may cause a hypertensive crisis, probably because of release of catecholamines from the tumor control such crises with phentolamine) sensitivity or intolerance to metoclopramide epileptics or patients receiving drugs likely to cause extrapyramidal reactions (the frequency and severity of seizures or extrapyramidal reactions may be increased). 

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