Abstract
Phenylethanolamine N-methyltransferase (PNMT) (EC 2.1.1.28, S-adenosyl-L-methionine: phenylethanolamine N-methyltransferase) is the enzyme that catalyzes the biosynthesis of norepinephrine [noradrenaline; (NA)] to epinephrine [adrenaline; (A)] in the presence of S-adenosyl-L-methionine (SAM) as the methyl donor. The enzyme is localized mainly in the adrenal medulla and in small amounts in discrete brain regions containing A cell bodies and nerve terminals. Adrenal PNMT has been extensively purified and well characterized, but the brain enzyme has not been well studied, although many similarities between them have been observed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Anderson P J. and D’Ioro A. (1968) Purification and properties of catechol-O-methyltransferase. Biochem. Pharmacol. 17, 1943–1949
Assicot M and Bohuon C (1969) Production of antibodies to catechol-O-methyltransferase (EC 2.1.1 6 ) of rat liver. Biochem Pharmacol. 18, 1893–1898.
Assicot M. and Bohuon C. (1970) Purification and studies of catechol-O-methyltransferase of rat liver Eur J Biochem. 12, 490–495.
Axelrod J. (1962) Purification and properties of phenylethanolamine N-methyltransferase. J. Biol Chem. 237, 1657–1660
Axelrod J. and Laroche M. J (1959) Inhibitor of O-methylation of epinephrine and norepinephrine in vitro and in vivo. Science 130, 800.
Axelrod J. and Tomchick R. (1958) Enzymatic O-methylation of epinephrine and other catechols J Blol Chem. 233, 702–705.
Axelrod J. and Vesell E S. (1970) Heterogeneity of N-and O-methyltransferase Mol Pharmacol. 6, 78–84.
Axelrod J,, Albers W., and Clemente C. D. (1959) Distribution of catechol-O-methyltransferase in the nervous system and other tissues J Neurochem. 5, 68–72
Bade P., Christ W., Rakow D, and Coper H. (1976) Comparison of catechol-O-methyltransferase from rat brain, erythrocytes and liver Life Sci 19, 1833–1844.
Baetge E E., Moon H M., Kaplan B B, Park D H., Reis D. J, and Joh T H. (1983) Identification of clones containing DNA complementary to phenylethanolamine N-methyltransferase mRNA Neurochem. Intl. 5, 611–617
Bakke O. M. (1970) O-methylation of simple phenols in the rat Acta Pharmacol. Toxicol. 28, 28–38
Ball P., Knuppen R., and Breuer H. (1971) Purification and properties of a catechol-O-methyltransferase of human liver Eur J Biochem. 21, 517–525.
Baron M, Gruen R., Levitt M., Hunter C, and Asms L. (1984) Erythrocyte catechol O-methyltransferase activity in schizophrenia: Analysis of family data Am J Psychiatry 141, 29–32
Belleau B. and Burba J (1963) Occupancy of adrenergic receptors and inhibition of catechol O-methyltransferase by tropolones J Med Chem 6, 755–759
Berenbeim D. M., Wong D. L., Masover S. J, and Ciaranello R D (1979) Regulation of synthesis and degradation of rat adrenal phenylethanolamine N-methyltransferase. III Stabilization of PNMT against thermal and tryptic degradation by S-adenosylmethionine. Mol. Pharmacol. 16, 482–490
Borchardt R T. (1981) Catechol O-Methyltransferase in Methods in Enzymology (Jakoby W. B., ed), vol 77, pp 267–272, Academic, New York.
Borchardt R T. and Cheng C F (1978) Purification and characterization of rat heart and brain catechol methyltransferase Biochem. Biophys. Acta 522, 49–62.
Borchardt R. T, Cheng C. F., Cooke P H., and Creveling C. R. (1974) The purification and kinetic properties of liver microsomal-catechol O-methyltransferase Life Sci. 14, 1089–1100
Borchardt R. T, Cheng C. F., and Thakker D R. (1975) Purification of catechol O-methyltransferase by affinity chromatography. Biochem Biophys. Res. Commun. 63, 69–77.
Borchardt R. T, Huber J A, and Houston M. (1982) Catechol-O-methyltransferase. 10 5-substituted 3-hydroxy-4-methoxybenzoic acid (isovanillic acids) and 5-substituted 3-hydroxy-4-methoxybenz-aldehydes (isovanillins) as potential inhibitors J Med Chem. 25, 258–271
Briggs M. H. and Briggs M. (1973) Hormonal Influences on erythrocyte catechol-O-methyl transferase activity in humans. Experientia 29, 278–280.
Caspers M L. (1982) Inhibition by lead of phenylethanolamine N-methyltransferase. Biochem. Pharmacol. 31, 1985–1988
Chen C. H., Klein D. C, and Robinson J. C (1974) Catechol-O-methyltransferase in rat placenta, human placenta and chonocarcinoma grown in culture. J. Reprod. Fertil 39, 407–410.
Ciaranello R. D, (1978a) Regulation of phenylethanolamine N-methyltransferase synthesis and degradation. I. Regulation by rat adrenal glucocorticoids. Mol. Pharmacol 14, 478–489.
Ciaranello R. D (1978b) Regulation of phenylethanolamine N-methyltransferase Biochem. Pharmacol. 27, 1895–1897.
Claranello R D., Barchas R. E, Byers G. S, Stemmle D. W, and Barchas J. D. (1969) Enzymatic synthesis of adrenaline in mammalian brain. Nature 221, 368–369.
Ciaranello R. D., Wong D. L., and Berenbeim D. M, (1978) Regulation of phenylethanolamine N-methyltransferase synthesis and degradation. II. Control of the thermal stability of the enzyme by an endogenous stabilizing factor Mol Pharmacol. 14, 490–501.
Cohn C K., Dunner D L., and Axelrod J. (1970) Reduced catechol-O-methyltransferase activity in red blood cells of women with primary affective disorder. Science 170, 1323–1324.
Connett R. J. and Kirshner N. (1970) Purification and properties of bovine phenylethanolamine N-methyltransferase. J. Blol. Ckem. 245, 329–334.
Coward J. K, Slisz E P, and Wu F Y. H. (1973) Kinetic studies on catechol O-methyltransferase Product inhibition and the nature of the catechol binding site. Biochemistry, 12, 2291–2297.
Creveling C R., Morris N, Shimizu H, Ong H. H., and Daly J. (1972) Catechol O-methyltransferase. IV. Factors affecting m-and p-methylation of substituted catechols. Mol. Pharmacol. 8, 398–409.
Creveling C R., Borchardt R. T, and Isersky C. (1973) Immunological Characterization of Catechol-O-Methyltransferase, in Frontiers in Catecholamine Research (Usdin E. and Snyder S. H., eds.), pp.117–119, Pergamon, New York.
Davidson J. R. T., McLeod M. N., Turnbull C. D., White H. L., and Feuer E J. (1979) Catechol-O-methyltransferase activity and classification of depression. Biol Psychiatry 14, 937–942.
Deguchi T. and Barchas J. (1971) Inhibition of transmethylations of biogenic amines by S-adenosylhomocysteine. Enhancement of transmethylation by adenosylhomocysteinase J. Biol. Chem. 246, 3175–3181.
Diaz-Borges J. M, Urbina M., and Drqan B. D. (1978) Some properties of phenylethanolamine N-methyltransferase of rat brain. Neurochem Res. 3, 15–26.
Dunner D L. (1979) The use of erythrocyte catechol-O-methyltransferase activity as a possible marker for vulnerability of affective disorder. Psychopharmacol. Bull. 15, 32
Dunner D. L, Cohn C. K., Gershon E S., and Goodwin F. K. (1971) Differential catechol-O-methyltransferase activity in unipolar and bipolar affective illness Arch. Gen. Psychiatry 25, 348–353.
Dunner D. L, Levitt M., Kumbaraci T., and Fieve R. R. (1977) Erythrocyte catechol-O-methyltransferase in primary affective disorder. Biol Psychiatry 12, 237–244.
Ebstein R., Belmaker R H., Benbenisty D, and Rimon R. (1976) Electrophoretic pattern of red blood cell catechol-O-methyltransferase in schizophrenia and manic-depressive illness. Biol. Psychiatry 11, 613–623.
Fahn S., Comi R, Snider S R., and Prasad A L. N (1979) Effect of a catechol-O-methyltransferase inhibitor, U-0521, with levo-DOPA admmistrauon Biochem. Pharmacol. 28, 1221–1225.
Floderus Y., Book J. A, and Wetterberg L. (1981) Erythrocyte catechol-O-methyltransferase activity in related families with schizophrenia. Clin Genet 19, 379–385.
Flohe L. (1974) Catechol-O-methyltransferase. Int Pharmacopsychiatry 9, 52–60.
Flohe L. and Schwabe K. P (1970) Kinetics of purified catechol-O-methyltransferase. Biochim. Biophys. Acta 220, 469–476.
Fuller R. W. (1982) Pharmacology of brain epinephrine neurons. Ann Rev. Pharmacol. Toxicol. 22, 31–55.
Fuller R. W. and Hemrick S. K (1979) Properties of norepinephrine N-methyltransferase from rat, cat, and chicken brain. Comp Biochem. Physiol 62C, 243–245.
Fuller R. W. and Hemrick-Luecke S. K. (1983) Species differences in epinephrine concentration and norepinephrine N-methyltransferase activity in hypothalamus and brain stem Comp. Biochem Physiol. 74C, 47–49.
Fuller R. W. and Hunt J. M (1967) Inhibition of phenylethanolamine N-methyltransferase by its product, epinephrine. Life Sci. 6, 1107–1112.
Fuller R. W. and Molloy B. B. (1977) Inhibition in vitro of norepinephrine N-methyltransferase by 2-aminotetralins, analogs of phenylethyl-amines with rigid conformation. Biochem Pharmacol 26, 446–447.
Fuller R. W., Warren B. J, and Molloy B. B. (1970) Substrate specificity of phenylethanolamine N-methyltransferase from rabbit adrenal. Biochim. Biophys Acta 222, 210–212.
Fuller R. W., Mills J., and Marsh M. M (1971) Inhibition of phenethanolamine N-methyltransferase by ring-substituted α-methyl-phenethylamines (amphetamines) J Med Chem 14, 322–325
Fuller R. W., Hemrick, S K., and Molloy B. B (1977) Position of a chloro substituent on phenylethanolamine as a determinant of methylation by rabbit adrenal norepinephrine N-methyltransferase. Res Commun. Chem. Pathol. Pharmacol 18, 577–580.
Gershon E. S. and Jonas W Z (1975) Erythrocyte soluble catechol-O-methyltransferase activity in primary affective disorder. A clinical and genetic study Arch Gen Psychiatry 32, 1351–1356
Gershon E. S., Lake C. R., and Leckman J F. (1979) Reduced Erythrocyte COMT and Plasma DBH Activities not Associated With Affective Disorders in Patients and Relatives, in Catecholamines: Basic and Clinical Frontiers (Usdin E., Kopin I. J., and Barchas J., eds.), pp, 1934–1936, Pergamon, New York
Gershon E. S., Goldin L. R, Lake C. R, Murphy D. L., and Guroff J. J. (1980) Genetics of Plasma Dopamine-β-Hydroxylase (DBH), Erythrocyte Catechol-O-Methyltransferase (COMT), and Platelet Monoamine Oxidase (MAO) in Pedigrees of Patients With Affective Disorders, in Enzymes and Neurotransmitters in Mental Disease (Usdin E., Sourkes T. L., and Youdim M B H., eds.), pp 281–299, John Wiley, New York
Gordonsmith R. H, Raxworthy M. J., and Gulliver P A. (1982) Substrate stereospecificity and selectivity of catechol-O-methyltransferase for DOPA, DOPA derivatives and α-substituted catecholamines. Biochem Pharmacol 31, 433–437.
Groshong R, Baldessarini R. J, Gibson D A., Lipinski J. F, Axelrod D, and Pope A (1978) Activities of type A and B MAO and catechol-O-methyltransferase in blood cells and skin fibroblasts of normal and chronic schizophrenic subjects Arch. Gen Psychiatry 35, 1198–1205
Grunewald G. L., Grindel J. M, Vincek W. C., and Borchardt R. T. (1975) Importance of the aromatic ring in adrenergic amines: Nonaromatic analogues of phenylethanolamine as substrates for phenylethanol-amine N-methyltransferase Mol Pharmacol. 11, 694–699
Guldberg H C and Marsden C A (1975) Catechol-O-methyl transferase: Pharmacological aspects and physiological role. Pharmacol Rev. 27, 135–206
Gulliver P. A, and Tipton K F (1978a) Direct extraction radioassay for catechol-O-methyl-transferase activity. Biochem Pharmacol 27, 773–775
Gulliver P A. and Tipton K F (1978b) The purification and properties of pig-liver catechol-O-methyl transferase. Eur. J. Biochem. 88, 439–444.
Gulliver P A and Tipton K F (1979) The purification and properties of pig brain catechol-O-methyltransferase J Neurochem. 32, 1525–1529.
Hoffman A. R., Ciaranello R D, and Axelrod J. (1975) Substrate and inhibitor kinetics of bovine phenylethanolamine N-methyltransferase. Biochem Pharmacol 24, 544–546
Hokfelt T, Fuxe K., Goldstein M, and Johansson O. (1974) Immunohistochemical evidence for the existence of adrenaline neurons in the rat brain. Brain Res 66, 235–251.
Huh M. M. O. and Friedhoff A. J. (1979) Multiple molecular forms of catechol-O-methyltransferase: Evidence for two distinct forms, and their purification and physical characterization. J. Biol. Chem. 254, 299–308
Joh T. H and Goldstein M (1973) Isolation and characterization of multiple forms of phenylethanolamine N-methyltransferase. Mol. Pharmacol. 9, 117–129
Kaplan G. P., Hartman B K., and Creveling C. R (1980) Anti-catechol-O-methyltransferase: Demonstration of specificity and immunological cross-reactivity with the enzyme from rat liver, kidney, brain and choroid plexuses Neurochem. Res. 5, 869–877
Kety S. S. (1967) Current biochemical approaches to schizophrenia N Engl. J. Med. 276, 325–331
Kirshner N. and Goodall McC. (1957) The formation of adrenaline from noradrenaline. Biochim. Biophys. Acta 24, 658–659
Kitabchi A E and Williams R. H. (1969) Phenylethanolamine N-methyltransferase in human adrenal gland Biochim Biophys Acta 178, 181–184.
Kitabchi A E., Solomon S S., and Williams R. H. (1968) Stimulatory effects of insulin and glucagon on phenylethanolamine N-methyltransferase of rat adrenal. Proc Soc. Exp Biol. Med. 127, 296–300.
Knuppen V R, Holler M., Tilmann D., and Breuer H. (1969) Interactions between oestrogens and catecholamines. II Effect of oestrogen on the degradation and methylation of adrenaline in mouse under in vivo conditions. Hoppe-Seylers J. Physiol Chem 350, 1301–1309.
Kondo Y., Nagatsu I, Karasawa N., Kojima H, and Nagatsu T. (1982) Immunohistocytochemical and biochemical studies on catecholamine-synthesizing enzymes of the lumbar sympathetic ganglia and sciatic nerves of bullfrogs. Biomed Res. 3, 197–206.
Krakoff L R. and Axelrod J. (1967) InhibitIon of phenylethanolamine N-methyltransferase. Biochem. Pharmacol. 16, 1384–1386.
Lee H. S., Schulz A. R., and Fuller R. W. (1974) Isolation of multiple forms of rabbit adrenal norepinephrine N-methyltransferase Arch Biochem. Biophys. 163, 735–741
Lee H. S., Schulz A. R., and Fuller R. W. (1978) Isolation and purification of rabbit adrenal norepinephrine N-methyltransferase isozyme. Arch. Biochem. Biophys. 185, 222–227.
Lew J. Y., Miyamoto T, and Goldstein M. (1976) Inhibition of PNMT activity in the adrenal glands and brainstem of rats. Biochem. Pharmacol. 25, 1433–1434.
Lew J. Y., Matsumoto Y., Pearson J, Goldstein M, Hokfelt T., and Fuxe K. (1977) Localization and characterization of phenylethanolamine N-methyltransferase in the brain of various mammalian species Brain Res. 119, 199–210.
Lewander T., Pongracz G. V, Backstrom M, and Wetterberg L (1981) Dopamine metabolism in red blood cells in schizophrenia Clin Genet. 19, 410–413
Liang N. Y, Tessel R E., Grunewald G L., and Borchardt R. T. (1982) Inhibitors of phenylethanolamine N-methyltransferase. 1. Effects of 2-cyclooctyl-2-hydroxyethylamine on rat brain and adrenal catechol-amine content and blood pressure. J Pharmacol. Exp. Ther 223, 375–381
Masover S. J., Berenbeim D. M., and Ciaranello R. D. (1979) Regulation of synthesis and degradation of rat adrenal phenylethanolamine N-methyltransferase. IV. Synergistic stabilization of the enzyme against thermal and tryptic degration by S-adenosylmethionine and biogenic amine substrates. Mol. Pharmacol 16, 491–503
Matthysse S. and Baldessarini R. J. (1972) S-adenosylmethionine and catechol-O-methyltransferase in schizophrenia. Am. J. Psychiatry 128, 1310–1312.
McGeer P. L and McGeer E. G. (1964) Formation of adrenaline by brain tissue. Biochem. Biophys. Res. Commun. 17, 502–507.
Molinoff P. B and Axelrod J. (1971) Biochemistry of catecholamines. Ann Rev. Biochem. 40, 465–499.
Molinoff P. B., Brimijoin S, Weinshilboum R., and Axelrod J. (1970) Neurally mediated increase in dopamine-β-hydroxylase activity. Proc. Natl. Acad Sci. USA 66, 453–458.
Park D. H and Joh T H. (1985) Species-specific charge forms of phenylethanolamine N-methyltransferase Brain Res., in press.
Park D H. and Joh T. H (1984) Activation of adrenal phenylethanolamine N-methyltransferase by phosphate. Biochem Pharmacol. 33, 2911–2913.
Park D. H., Baetge E. E, Kaplan B B., Albert V. R, Reis D. J, and Joh T. H. (1982) Different forms of adrenal phenylethanolamine N-methyltransferase Species-specific posttranslational modification. J. Neurochem 38, 410–414.
Pendleton R. G, Kaiser C., and Gessner G. (1976) Studies on adrenal phenylethanolamine N-methyltransferase (PNMT) with SKF 64139, a selective inhibitor J Pharmacol. Exp Ther. 197, 623–632.
Pendleton R G., Gessner G, Weiner G, Jenkins B., Sawyer J., Bondinell W., and Intoccia A (1979) Studies on SKF 29661, an organ-specific inhibitor of phenylethanolamine N-methyltransferase. J. Pharmacol. Exp. Ther 208, 24–30.
Pohorecky L A. and Baliga B S (1973) Purification and properties of rat adrenal phenylethanolamine N-methyl transferase. Arch. Biochem. Biophys 156, 703–711.
Pohorecky L. A. and Wurtman R. J. (1971) Adrenocortical control of epinephrine synthesis. Pharmacol. Rev. 23, 1–35.
Pohorecky L. A., Zigmond M, Karten H., and Wurtman R. J. (1969) Enzymatic conversion of norepinephrine to epinephrine by the brain. J Pharmacol Exp Ther. 165, 190–195.
Pohorecky L A., Baliga B S., Wurtman R. J., and Bartter F C (1973) Adrenocortical control of catecholamine metabolism in the dog adrenal medulla. Relationship to protein synthesis. Endocrinology 93, 566–574.
Poitou P., Assicot M., and Bohuon C. (1974) Soluble and Membrane catechol-O-methyltransferase in red blood cells of schizophrenic patients. Biomedicine 21, 91–93.
Rafferty M. F. and Grunewald G. L. (1982) The remarkable substrate activity for phenylethanolamine N-methyltransferase of some conformationally defined phenylethylamines lacking a side-chain hydroxyl group. Mol. Pharmacol 22, 127–132
Raxworthy M. J., Gulliver P. A., and Hughes P J (1982) The cellular location of catechol-O-methyltransferase in rat liver. Naunyn Schmiedebergs Arch Pharmacol 320, 182–188.
Rivett A. J. and Roth J. A. (1982) Kinetic studies on the O-methylation of dopamine by human brain membrane-bound catechol O-methyltransferase Biochemistry 21, 1740–1742.
Rivett A. J., Francis A, and Roth J A. (1983a) Distinct cellular localization of membrane-bound and soluble forms of catechol-O-methyltransferase in brain. J Neurochem 40, 215–219
Rivett A. J., Francis A., and Roth J. A. (1983b) Localization of membrane-bound catechol-O-methyltransferase. J. Neurochem 40, 1494–1496.
Roth J A. (1980) Presence of membrane-bound catechol-O-methyltransferase in human brain. Biochem. Pharmacol 29, 3119–3122.
Saavedra J. M., Palkovits M., Brownstein M J., and Axelrod J (1974) Localization of phenylethanolamine N-methyltransferase in the rat brain nuclei. Nature 248, 695–696.
Saavedra J. M., Brownstein M. J., and Palkovits M. (1976) Distribution of catechol-O-methyltransferase, histamine N-methyltransferase and monoamine oxidase in specific areas of the rat brain Brain Res. 118, 152–156
Senoh S., Daly J, Axelrod J., and Witkop B. (1959) Enzymatic p-O-methylation by catechol O-methyl transferase J Am. Chem Soc. 81, 6240–6245.
Shopsin B., Wilk S., Gershon S., Roffman M, and Goldstein M. (1973) Collaborative Psychopharmacologic Studies Exploring Catecholamine Metabolism in Psychiatric Disorders, in Frontiers in Catecholamine Research (Usdin E. and Snyder S. H., eds.), Pergamon, New York.
Teitelman G, Skaper S, Baker H, Park D. H., Joh T. H., and Adler R. (1984) Expression of phenylethanolamine N-methyltransferase in sympathetic neurons and extraadrenal chromaffin tissue of chick embryos in vivo and in vitro. Dev. Brain Res 13, 283–291.
Thoenen H., Mueller R A., and Axelrod J. (1970) Neuronally dependent induction of phenylethanolamine N-methyltransferase by 6-hydroxydopamine. Biochem Pharmacol. 19, 669–673.
Tunnicliff G and Ngo T T (1983) Kinetics of rat brain soluble catechol-O-methyltransferase and its inhibition by substrate analogues. Int J Biochem. 15, 733–738.
Vogel W. H., Lewis L. E., and Boehme D. H (1976) Phenylethanolamine N-methyltransferase activity in various areas of human brain, tissues and fluids. Brain Res. 115, 357–359.
White H L. and Wu J. C. (1975) Properties of catechol O-methyltransferases from brain and liver of rat and human. Biochem. J. 145, 135–143.
White H. L, McLeod M. N, and Davidson J. R. T. (1976) Catechol O-methyltransferase in red blood cells of schizophrenic, depressed and normal human subjects, Br J. Psychiatry 128, 184–187.
Wurtman R. J and Axelrod J. (1966) Control of enzymatic synthesis of adrenaline in the adrenal medulla by adrenal cortical steroids. J Biol. Chem. 241, 2301–2305.
Wurtman R. J., Axelrod J,, Vesell E. S., and Ross G. T. (1968) Species differences in inducibility of phenylethanolamine N-methyltransferase. Endocrinology 82, 584–590.
Yu P. H. (1978) Phenylethanolamine N-methyltransferase from the brain and adrenal medulla of the rat. A comparison of their properties. Neurochem. Res 3, 755–762
Zurcher G. and Da Prada M. (1982) Rapid and sensitive single-step radiochemical assay for catechol-O-methyltransferase. J Neurochem 38, 191–195.
Author information
Authors and Affiliations
Editor information
Rights and permissions
Copyright information
© 1986 The Humana Press Inc.
About this protocol
Cite this protocol
Park, D.H. (1986). Monoamine Methyltransferases. In: Boulton, A.A., Baker, G.B., Yu, P.H. (eds) Neurotransmitter Enzymes. Neuromethods, vol 5. Humana Press. https://doi.org/10.1385/0-89603-079-2:117
Download citation
DOI: https://doi.org/10.1385/0-89603-079-2:117
Publisher Name: Humana Press
Print ISBN: 978-0-89603-079-4
Online ISBN: 978-1-59259-610-2
eBook Packages: Springer Protocols