Norepinephrine oxidation

Tyrosine oxidation Dopamine Norepinephrine Oxidative N-dealkylation Methane Methanol Ammonia —> Hydroxylamine... 

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

The solubility of the resulting product may dictate the choice of solvent. Reductive alkylation of norepinephrine with a series of keto acids proceeded smoothly over platinum oxide in methanol-acetic acid mixtures. However, when n = 4 or 5, the product tended to precipitate from solution, making catalyst separation difficult. The problem was circumvented by using glacial acetic acid as solvent 38). 

Analogous side-chain oxidations occur in various biosynthetic pathways. The neurotransmitter norepinephrine, for instance, is biosynthesized from dopamine by a benzylic hydroxylation reaction. The process is catalyzed by the copper-containing enzyme dopamine /3-monooxygenase and occurs by a radical mechanism. A copper-oxygen species in the enzyme first abstracts the pro-R benzylic hydrogen to give a radical, and a hydroxyl is then transferred from copper to carbon. 

Dopamine (5-hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines norepinephrine and epinephrine from tyrosine in the adrenal medulla and central nervous system. During hy-droxylation, the Cu+ is oxidized to Cu " reduction back... 

Nitric oxide, a vasodilatory hormone released by the endothelium, is found in higher concentrations in HF patients and provides two main benefits in HF vasodilation and neurohormonal antagonism of endothelin.9 Nitric oxide s production is affected by the enzyme inducible nitric oxide synthetase (iNOS), which is up-regulated in the setting of HF, likely due to increased levels of angiotensin II, norepinephrine, and multiple cytokines. In HF, the physiologic response to nitric oxide appears to be blunted, which contributes to the imbalance between vasoconstriction and vasodilation. 

B42. Booke, M., Hinder, F., McGuire, R., Traber, L. D., and Traber, D. L Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep. Crit. Care Med. 24, 835-844 (1996). 

Against this backdrop, researchers reported evidence that iproniazid, the antitubercular drug that was to become the first antidepressant, might increase norepinephrine and serotonin levels in the brain. How did it have this effect Recall that some of the neurotransmitter molecules released by a neuron are destroyed by enzymes in the synaptic cleft between the sending presynaptic neuron and the receiving postsynaptic neuron. When the neurotransmitter is a monoamine - like norepinephrine and serotonin - this process is called monoamine oxidase (MAO). As early as 1952 researchers at the Northwestern University Medical School in Chicago reported that iproniazid inhibited the oxidation of monoamines. This meant that iproniazid was a... 

Here then is the logic behind the first version of the chemical-imbalance theory. Iproniazid is a monamine oxidase inhibitor - it inhibits the oxidation of norepinephrine and serotonin in the synapses, thereby leaving more of these neurotransmitters available in the brain. When depressed people take iproniazid, they get better. Therefore insufficient norepinephrine and/or serotonin causes depression.12... 

Many hormones and other blood-borne substances (including drugs) also alter contractile activity of smooth muscle. Some of the more important substances include epinephrine norepinephrine angiotensin II vasopressin oxytocin and histamine. Locally produced substances that may alter contraction in the tissue in which they are synthesized include nitric oxide prostaglandins leukotrienes carbon dioxide and hydrogen ion. 

Kodama, T. Koyama, Y. (2006). Nitric oxide from the laterodorsal tegmental neurons its possible retrograde modulation on norepinephrine release from the axon terminal of the locus coeruleus neurons. Neuroscience 138, 245-56. 

A particular interest for clinical applications was a possibility for detection of dopamine by its oxidation on nickel [19], cobalt [65], and osmium [66] hexacyanofer-ates. Except for oxidation of dopamine, cobalt and osmium hexacyanoferrates were active in oxidation of epinephrine and norepinephrine. For clinical analysis it is also important to carry out the detection of morphine on cobalt [67] and ferric [68] hexacyanoferrates, as well as the detection of oxidizable amino acids (cystein, methionine) by manganous [69] and ruthenium [70] hexacyanoferrate-modified electrodes. In general, oxidation of thiols was first shown for Prussian blue [71] and nickel hexacyanoferrate [72], This approach has been used for the detection of thiols in rat striatum microdialysate [73], Alternatively, the detection of thiocholine with Prussian blue was employed for pesticide determination in acetylcholine-esterase test [74],... 

Figure 15.14 illustrates a typical voltammetric result for the determination of dopamine in the presence of ascorbic acid with a CNT-modified electrode. The selective voltammetric detection of uric acid [82] or norepinephrine [83] in the presence of ascorbic acid has been demonstrated with a (3-cyclodextrin-modified electrodes incorporating CNTs. Ye et al. [84] have studied the electrocatalytic oxidation of uric acid and ascorbic acid at a well-aligned CNT electrode, which can be used for the selective determination of uric acid in the presence of ascorbic acid. The simultaneous determination of dopamine and serotonin on a CNT-modified GC electrode has also been described [85],... 

Figure 4-3 shows the influence of organic modifiers on the voltammogram of norepinephrine (nor) in different solvents A, B and C (the dashed lines show the oxidation of the solvents). Solvent A water, 0.02 M sodium acetate B methanol, 0.02 M sodium acetate C acetone/water 90/10, 0.02 M ammonium perchlorate. Solvents A, B and C pH 7, 0.005 M NaCl. 

The biogenic amines are the preferred substrates of MAO. The enzyme comes in two flavors, MAO-A and MAO-B, both of which, like FMO, rely on the redox properties of FAD for their oxidative machinery. The two isoforms share a sequence homology of approximately 70% (81) and are found in the outer mitochondrial membrane, but they differ in substrate selectivity and tissue distribution. In mammalian tissues MAO-A is located primarily in the placenta, gut, and liver, while MAO-B is predominant in the brain, liver, and platelets. MAO-A is selective for serotonin and norepinephrine and is selectively inhibited by the mechanism-based inhibitor clorgyline (82). MAO-B is selective for /1-phcncthylaminc and tryptamine, and it is selectively inhibited by the mechanism-based inhibitors, deprenyl and pargyline (82) (Fig. 4.32). Recently, both MAO-A (83) and MAO-B (84) were structurally characterized by x-ray crystallography. 

In contrast, much is known about the catabolism of catecholamines. Adrenaline (epinephrine) released into the plasma to act as a classical hormone and noradrenaline (norepinephrine) from the parasympathetic nerves are substrates for two important enzymes monoamine oxidase (MAO) found in the mitochondria of sympathetic neurones and the more widely distributed catechol-O-methyl transferase (COMT). Noradrenaline (norepinephrine) undergoes re-uptake from the synaptic cleft by high-affrnity transporters and once within the neurone may be stored within vesicles for reuse or subjected to oxidative decarboxylation by MAO. Dopamine and serotonin are also substrates for MAO and are therefore catabolized in a similar fashion to adrenaline (epinephrine) and noradrenaline (norepinephrine), the final products being homo-vanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) respectively. 

The use of HPLC to analyze biogenic amines and their acid metabolites is well documented. HPLC assays for classical biogenic amines such as norepinephrine (NE), epinephrine (E), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin) and their acid metabolites are based on several physicochemical properties that include a catechol moiety (aryl 1,2-dihydroxy), basicity, easily oxidized nature, and/or native fluorescence characteristics (Anderson, 1985). Based on these characteristics, various types of detector systems can be employed to assay low concentrations of these analytes in various matrices such as plasma, urine, cerebrospinal fluid (CSE), tissue, and dialysate. 

The coenzyme tetrahydrofolate (THF) is the main agent by which Ci fragments are transferred in the metabolism. THF can bind this type of group in various oxidation states and pass it on (see p. 108). In addition, there is activated methyl, in the form of S-adenosyl methionine (SAM). SAM is involved in many methylation reactions—e. g., in creatine synthesis (see p. 336), the conversion of norepinephrine into epinephrine (see p. 352), the inactivation of norepinephrine by methylation of a phenolic OH group (see p. 316), and in the formation of the active form of the cytostatic drug 6-mercaptopurine (see p. 402). 

The mechanism of antidepressive action of this series of drugs is likely associated with their inhibition of the oxidizing deamination process of the neurotransmitters norepinephrine, epinephrine, dopamine, and serotonin, which participate in the transmission of nerve excitement in the CNS. A major drawback of these drugs is the high toxicity associated with their inhibition of not only MAO, but also a number of other nonspecific enzymes. 

Zhang C, Davies MF, Guo TZ, Maze M (1999) The analgesic action of nitrous oxide is dependent on the release of norepinephrine in the dorsal horn of the spinal cord. Anesthesiology 91,1401-1407... 

The CL emission of Scheme 3 catalyzed by HRP can be applied to the quantitative analysis of catecholamines, such as dopamine (68), epinephrine (132), L-DOPA (30), norepinephrine (133), deoxyepinephrine (134) isoproterenol (135) and dihydroxybenzy-lamine (136), in a FIA system, after undergoing the oxidation shown for dopamine (68) in equation 20. The mechanism of this process is not totally clear however, the CL yields of equation 20 depend upon the pH of the system (pH 9 is convenient and is achieved by adjusting the concentration of imidazole), the temperature (60 °C is adequate) and the structure of the analyte (a calibration curve is needed for each one). Taking 68 as reference (100%) the CL yields after 30 min incubation (achieved by controlling the flow through a long capillary mbe) are as shown in equation 42 A5i... 

Monoamine oxidase (MAO) inhibitors block the oxidative deamination of monoamines, i.e. norepinephrine and serotonin by inhibiting monoamine oxidase type A (MAO-A) and dopamine also by monoamine oxidase type B (MAO-B) inhibition, thereby increasing these neurotransmittors at their receptors in the brain and in the periphery. MAO-A... 

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. 

Monoamine oxidase A (MAOA) oxidizes 5-HT, norepinephrine as well as dopamine, and is expressed in a cell type-specific manner. Abnormalities in... 

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