Summary
2-Phenylethylamine is an endogenous constituent of human brain and is implicated in cerebral transmission. It is also found in certain foodstuffs and may cause toxic side-effects in susceptible individuals. Metabolism of 2-phenylethylamine to phenylacetaldehyde is catalyzed by monoamine oxidase and the oxidation of the reactive aldehyde to its acid derivative is catalyzed mainly by aldehyde dehydrogenase and perhaps aldehyde oxidase, with xanthine oxidase having minimal transformation. The present investigation examines the metabolism of 2-phenylethylamine to phenylacetaldehyde in liver slices and compares the relative contribution of aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase activity in the oxidation of phenylacetaldehyde with precision-cut fresh liver slices in the presence/absence of specific inhibitors of each enzyme. In liver slices, phenylacetaldehyde was rapidly converted to phenylacetic acid. Phenylacetic acid was the main metabolite of 2-phenylethylamine, via the intermediate phenylacetaldehyde. Phenylacetic acid formation was completely inhibited by disulfiram (specific inhibitor of aldehyde dehydrogenase), whereas isovanillin (specific inhibitor of aldehyde oxidase) inhibited acid formation to a lesser extent and allopurinol (specific inhibitor of xanthine oxidase) had little or no effect. Therefore, in liver slices, phenylacetaldehyde is rapidly oxidized by aldehyde dehydrogenase and aldehyde oxidase with little or no contribution from xanthine oxidase.
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Nakajima T., Kakimoto Y., Sano I. (1964): Formation of beta- phenylethylamine in mammalian tissue and its effect on motor activity in the mouse. J. Pharmacol. Exp. Ther., 143, 319–325.
Durden D.A., Philips S.R. (1980): Kinetic measurements of the turnover rates of phenylethylamine and tryptamine in vivo in the rat brain. J. Neurochem., 34, 1725–1732.
Henry D.P., Russell W.L., Clemens J.A., Plebus L.A. (1988): Phenylethylamine and p-tyramine in the extracellular space of the rat brain: quantification using a new radioenzymatic assay and in situ microdialysis. In: Boulton A.A., Juorio A.V., Downer R.G.H. (eds). Trace amines: comparative and clinical neurobiology. Humana Press, Clifton, NJ, 239–250.
Paterson I.A., Jurio A.V., Boulton A.A. (1990): 2-Phenylethylamine: a modulator of catecholamine transmission in the mammalian central nervous system. J. Neurochem., 55, 1827–1837.
Wyatt R.J., Gillin J.C., Stoff D.M., Moja E.A., Tinklenberg J.R. (1977): In: Usdin E., Barchas J., Hamburg D. (eds). Neuroregulators and psychiatric disorders. Oxford University Press. New York, 31.
Boulton A.A., Juorio A.V., Paterson I.A. (1990): Phenylethylamine in CNS: effects of monoamine oxidase inhibiting drugs, deuterium substitution and lesions and its role in the neuromodulation of catecholaminergic neurotransmission. J. Neural Transm. Suppl., 29, 119–129.
Dyck, L.E., Yang C.R., Boulton A.A. (1983): The biosynthesis of p-tyramine, m-tyramine, and β-phenylethylamine by rat striatal slices. J. Neurochem. Res., 10, 211–220.
Barroso N., Rodriguez M. (1996): Action β-phenylethylamine and related amines on nigrostriatal dopamine neurotransmission. Eur. J. Pharmacol., 297, 195–203.
Fischer E. (1975): The phenethylamine hypothesis of thymic homeostasis. Biol. Psychiatry, 10, 667–673.
Sabelli H.C., Borison R.L., Diamond B.I., Havdala H.S., Narasimhachari N. (1977): Phenylthylamine and brain function. Biochem. Pharmacol., 27, 1707–1711.
Sandler M., Youdim M.B., Hanington E. (1974): A phenylethylamine oxidizing defect in migraine. Nature, 250, 335–337.
Millichap J.G., Yee M.M. (2003): The diet factor in pediatric and adolescent migraine. Pediatr. Neurol., 28, 9–15.
Martin V.T., Behbehani M.M. (2001) Headache: Toward a rational understanding of migraine trigger factors. Med. Clin. N. Am., 85, 1–20.
Quian M., Reineccius G. (2002) Identification of aroma compounds in Parmigiamo-Reggiano cheese by gas chromatography/olfactometry. J. Dairy Sci., 85, 1362–1369.
Hyotylainen T., Savola N., Lehtonen P., Riekkola M.L. (2001): Determination of biogenic amines in wine by multidimensional liquid chromatography with online derivatisation. Analyst, 126, 2124–2127.
Aznar M., Lopez R., Cacho J., Ferreira V. (2003) Prediction of aged red wine aroma properties from aroma chemical composition: Partial least squares regression models. J. Agric. Food Chem., 51, 2700–2707.
Salach J.I. (1979): Monoamine oxidase from beef liver mitochondria: simplified isolation procedure, properties, and determination of its cysteinyl flavin content. Arch. Biochem. Biophys., 192, 128–137.
Houslay M.D., Tipton K.F. (1974): A kinetic evaluation of monoamine oxidase activity in the rat liver mitochondrial outer membranes. Biochem. J., 139, 645–652.
Wouters J. (1998): Structural aspects of monoamine oxidase and its reversible inhibition., Curr. Med. Chem., 5, 137–162.
Feldman R.I., Weiner H. (1972): Horse liver aldehyde dehydrogenase. I. Purification and characterization. J. Biol. Biochem., 247, 260–266.
Panoutsopoulos G.I. (1994): In: Hepatic Oxidation of Aromatic Aldehydes, PhD Thesis, University of Bradford, Bradford, UK.
Smith P.F., Krack G., McKee R.L., Johnson D.G., Gandolfi A.J., Hruby, V.J., Krumdieck C.L., Brendel K. (1986): Maintenance of adult rat liver slices in dynamic organ culture. In Vitro Cell. Dev. Biol., 22, 706–712.
Sipes I.G., Fisher R.L., Smith P.F., Stine E.R., Gandolfi A.J., Brendel K. (1987): A dynamic liver culture system: a tool for studying chemical biotransformation and toxicity. Arch. Toxicol. Suppl., 11, 20–33.
Youdim M.B., Finberg J.P.M. (1991): New directions in monoamine oxidase A and B selective inhibitors and substrates. Biochem. Pharmacol., 41, 155–162.
Goridis C, Neff N.H. (1971): Monoamine oxidase in sympathetic nerves: a transmitter specific enzyme type. Br. J. Parmacol., 43, 814–818.
Egashira T., Ekstedt B., Oreland L. (1976): Inhibition by clorgyline and deprenyl of the different forms of monoamine oxidase in rat liver mitochondria. Biochem. Pharmacol., 25, 2583–2586.
Neff N.H., Yang H.Y.T. (1974): Another look at the monoamine oxidases and the monoamine oxidase inhibitor drugs. Life Sci., 14, 2061–2074.
Fuller R.W., Warren B.J., Molloy B.B. (1970): Selective inhibition of monoamine oxidase in rat brain mitochondria. Biochem. Pharmacol., 19, 2934–2936.
Shaw S., Jayatilleke E. (1992): The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury. Life Sci., 50, 2045–2052.
Pietruszco R. (1989): In Biochemistry and Physiology of substance abuse (Watson R.R., Ed.) Vol. I, pp89–127, CRC Press, Boca Raton, FL.
Klyosov A.A. (1996): Kinetics and specificity of human liver aldehyde dehydrogenases toward aliphatic, aromatic, and fused polycyclic aldehydes. Biochemistry, 35, 4457–4467.
Kaminski Z.W., Jezewska M.M. (1982): Involvement of a single thiol group in the conversion of the NAD+-dependent activity of the rat liver oxidoreductase to the O2-dependent activity. Biochem. J., 207, 341–346.
Waud W.R., Rajagopalan K.V. (1976): Purification and properties of the NAD+-dependent (type D) and O2-dependent (type O) forms of the rat liver xanthine dehydrogenase. Arch. Biochem. Biophys., 172, 354–364.
Delia Corte E., Stripe F. (1972): The regulation of rat liver xanthine oxidase: Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J., 126, 739–745.
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Panoutsopoulos, G.I., Kouretas, D., Gounaris, E.G. et al. Metabolism of 2-phenylethylamine and phenylacetaldehyde by precision-cut guinea pig fresh liver slices. European Journal of Drug Metabolism and Pharmacokinetics 29, 111–118 (2004). https://doi.org/10.1007/BF03190585
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DOI: https://doi.org/10.1007/BF03190585