Metabolism amines

Trace Amines. Figure 1 The main routes of trace amine metabolism. The trace amines (3-phenylethylamine (PEA), p-tyramine (TYR), octopamine (OCT) and tryptamine (TRP), highlighted by white shading, are each generated from their respective precursor amino acids by decarboxylation. They are rapidly metabolized by monoamine oxidase (MAO) to the pharmacologically inactive carboxylic acids. To a limited extent trace amines are also A/-methylated to the corresponding secondary amines which are believed to be pharmacologically active. Abbreviations AADC, aromatic amino acid decarboxylase DBH, dopamine b-hydroxylase NMT, nonspecific A/-methyltransferase PNMT, phenylethanolamine A/-methyltransferase TH, tyrosine hydroxylase. 

Biogenic amines are decarboxylated derivatives of tyrosine and tryptophan that are found in animals from simple invertebrates to mammals. These compounds are found in neural tissue, where they function as neurotransmitters, and in non-neural tissues, where they have a variety of functions. The enzymes involved in biogenic amine synthesis and many receptors for these compounds have been isolated from both invertebrate and vertebrate sources. In all cases, the individual proteins that effect biogenic amine metabolism and function show striking similarity between species, indicating that these are ancient and well-conserved pathways. 

Wright, T. (1987). The genetics of biogenic amine metabolism, sclerotization and melanization in Drosophila melanogaster. Genetics 24 127-222. 

Morgan, M.E., Gibb, J.W. Short-term and long-term effects of methamphetamine on biogenic amine metabolism in extra-striatal dopaminergic nuclei. Neumpharmacology. 19 989, 1980. 

Azo dye-containing wastewaters seems to be one of the most polluted wastewaters, which require efficient decolorization and subsequent aromatic amine metabolism. On the basis of the available literature, it can be concluded that anaerobic-aerobic SBR operations are quite convenient for the complete biodegradation of both azo dyes and their breakdown products. Nevertheless, like the other methods used for biological treatment, SBRs treating colored wastewaters have some limitations. Presence of forceful alternative electron acceptors such as nitrate and oxygen, availability of an electron donor, microorganisms, and cycle times of anaerobic and aerobic reaction phases can be evaluated as quite significant. 

Hein DW. Molecular genetics and function of NAT1 and NAT2 role in aromatic amine metabolism and carcinogenesis. Mutat Res 2002 506-507 65-77. 

Okonmah AD, Brown JW, Blyden GT, Soliman KF. (1988). Prenatal effects of acute harmaline exposure on fetal brain biogenic amine metabolism. Pharmacology. 37(3) 203-8. 

As a result of a high index of clinical suspicion and, on occasion, supporting biochemical data from other investigations, one of the first specialist investigations to ascertain whether a patient has an inborn error of biogenic amine metabolism is, as mentioned above, analysis of the CSF concentrations of HVA and 5HIAA. This is often performed in conjunction with the measurement of 3-methyldopa (3-MD), also known as 3-methoxytyrosine. 3-MD is formed from L-dopa via COMT activity and accumulates in conditions where aromatic amino acid decarboxylase activity is impaired. The chemical structures of HVA, 5HIAA and 3-MD are shown in Fig. 6.2.1. 

Table 6.2.2 Typical CSF profiles of HVA, 5HIAA and 3-methyldopa (3-MD) for the inborn errors of metabolism associated with a disruption of biogenic amine metabolism. A downward-pointing arrow indicates that a particular metabolite is below the established reference range. An upward pointing arrow is indicative that a metabolite is above the established reference range. WR indicates that the concentration of the metabolite is likely to be within the reference range. AADC Aromatic amino acid decarboxylase, PNPO pyridox(am)ine-5 -phosphate oxidase...

Other medications that could theoretically lead to the erroneous suggestion that a patient has an inborn error of biogenic amine metabolism include serotonin reuptake inhibitors, MAO and COMT inhibitors. 

Whenever a CSF profile is suggestive of a disruption of dopamine and/or serotonin metabolism, analysis of the pterin profile is extremely important in order to ascertain whether disruption of biogenic amine metabolism is directly related to alteration in BH4 availability. 

Secondary alicyclic amines, such as pyrrolidine and piperidine, have many properties typical of the corresponding aliphatic amines. Metabolic oxidation at secondary alicyclic nitrogens results in the formation of hydroxylamines, which may then undergo enzymic or non-enzymic conversion to nitrones, and in some cases to nitroxide radicals. For example, the 2-substituted piperidino derivative (- )-anabasine (1), a tobacco alkaloid, is metabolized initially to a hydroxylamine (2) and then to the nitrone (3), when incubated with liver and... 

Murray S, Lake BG, Gray S, Edwards AJ, Springall C, Bowey EA, Williamson G, Boobis AR, Gooderham NJ. Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man. Carcinogenesis 2001 22 1413-1420. 

Moore RY (1970) Brain lesions and amine metabolism. Rev Neurobiol 73 67-71. 

Pugsley TA, Lippmann W. 1979. Effect of acute and chronic treatment of tandamine, a new heterocyclic antidepressant, on biogenic amine metabolism and related activities. Naunyn Schmiedebergs Arch. Pharmacol. 308 239 17... 

The most likely candidate for the phosphoethanolamine donor is phosphatidylethanol-amine. Metabolic radiolabeling studies demonstrate that [ H]ethanolamine is incorporated into CDP-phosphoethanolamine before it is transferred to phosphatidylethanolamine and attached to the GPI core glycan. CDP-ethanolamine, however, is not a donor since it is not required for, nor does it affect, GPI anchor biosynthesis [62]. Consistent with this observation is the lack of [ HJglucosamine incorporation into GPI anchors in yeast mutants that do not synthesize phosphatidylethanolamine from CDP-ethanolamine yet can construct GPI anchors [88]. Direct evidence for a phosphatidylethanolamine donor is still lacking. 

Imipramine, a substance with a structure similar to the phenothiazines (Figure 5) but varying in that the ring is a dibenzazepine rather than a phenothiazine, was the first active antidepressant of the nonmomoamine oxidase inhibitor series of agents. It, like the monoamine oxidase inhibitors, is effective in less than half the patients treated. Its mode of action is not clearly understood, but there is increasing evidence that it too exerts an effect on catechol amine metabolism (19). Although serious toxic effects have been uncommon, excitement, jaundice, and blood dyscrasias have occurred (17). 

Turesky, R.J. (2002) Heterocyclic aromatic amine metabolism, DNA adduct formation, mutagenesis, and carcinogenesis. Drug Metab. Rev., 34, 625-650. 

Subhash MN, Padmashree TS. 1991. Effect of manganese on biogenic amine metabolism in regions of the rat brain. Food Chem Toxicol 29 579-582. 

The greater importance of 0-methylation in the inactivation of circulating catechol amines is due to the fact that, in the liver, where most of the breakdown takes place, the activity of catechol 0-methyltransferase is very much higher than that of monoamine oxidase. This relationship does not, however, apply to all other organs in the heart, for instance, monoamine oxidase is about five times as active as the 0-methyltransferase, and monoamine oxidase also plays a part in catechol amine metabolism in the brain. 

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