Amine oxidases and their endogenous substrates (with special reference to monoamine oxidase and the brain)

  • P. C. Waldmeier
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 23)


The roles of MAO, BzO, DAO and PAO in the metabolism of endogenous substrates and the functional implications of their action and inhibition is reviewed, the emphasis being on MAO on one hand and on brain on the other. The major issues are the following:
  1. 1.

    There is no discrete subdivision into substrates selective for MAO-A, MAO-B, or mixed ones, but rather a continuum.

  2. 2.

    Tissue differences in substrate specificity are not likely to be due to molecular variability of MAO. For the deamination of DA, 5-HT and PEA at least, the relative participation of either MAO form in a given tissue is primarily determined by the relative abundance of the two forms; only at 10-5M and above, substrate concentration begins to matter also.

  3. 3.

    In vivo, compartmentation is of paramount importance: since there seems to be more MAO-A than B inside monoaminergic neurons, DA, 5-HT and NA are predominantly metabolized by MAO-A if metabolism occurs mainly intraneuronally. Conversely, since MAO-B is more abundant extraneuronally, e.g. in glia cells, the relative participation of this form increases if a significant portion of these amines is deaminated outside monoaminergic neurons.

  4. 4.

    In vivo, monoamine deamination is reduced concomitantly with the degree of MAO inhibition, whereas signs of increased transmitter function are only observed if enzyme inhibition is at least 80%. This is likely to be the result of the action of compensatory mechanisms such as feedback inhibition of transmitter release and synthesis.

  5. 5.

    BzO is particularly abundant in vascular tissue, lung and bone. Low levels are found in brain. Endogenous substrates and physiological function are not known. DAO also occurs only in minimal amount in brain, if at all. Its principal substrates are histamine and the polyamines, and the disposal of these amines is probably its main function. Of the PAO’s, the type of enzyme found in the rat liver attacks the secondary amino groups and may have a more prominent role in the metabolism of polyamines in the brain than in the periphery. Bovine plasma PAO, which attacks primary amino groups, is only found in the serum of ruminants, but not other species. Its function in the metabolism of polyamines is not known.



Monoamine Oxidase Endogenous Substrate Amine Oxidase Diamine Oxidase Monoamine Oxidase Activity 
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  1. Achee FM, Togulga G, Gabay S (1974) Studies of monoamine oxidases: properties of the enzyme in bovine and rabbit brain mitochondria. J Neurochem 22: 651–661PubMedCrossRefGoogle Scholar
  2. Andree TH, Clarke DE (1981) The isolated perfused rat brain preparation in the study of monoamine oxidase and benzylamine oxidase: lack of selective brain perfusion. Biochem Pharmacol 30: 959–965PubMedCrossRefGoogle Scholar
  3. Arnaiz GR, DeRobertis CD (1962) Cholinergic and noncholinergic nerve endings in the rat brain. II. Subcellular localization of monoamine oxidase and succinate dehydrogenase. J Neurochem 9: 503–508CrossRefGoogle Scholar
  4. Azzaro AJ, King J, Kotzuk J, Schoepp DO, Frost J, Schochet S (1985) Guinea pig striatum as a model of human dopamine deamination: the role of monoamine oxidase isoenzyme ratio, localization and affinity for substrate in synaptic dopamine metabolism. J Neurochem 45: 949–956PubMedCrossRefGoogle Scholar
  5. Bolkenius FN, Bey P, Seller N (1985) Specific inhibition of polyamine oxidase in vivo is a method for the elucidation of its physiological role. Bio-chim Biophys Acta 838: 69–76CrossRefGoogle Scholar
  6. Carlsson A, Fowler CJ, Magnusson T, Oreland L, Wiberg A (1981) The activities of monoamine oxidase-A and -B, succinate dehydrogenase and acid phosphatase in the rat brain after hemitransection. Naunyn-Schmiede-berg’s Arch Pharmacol 316: 51–55CrossRefGoogle Scholar
  7. Dahlstrom A, Haggendal J, Hokfelt T (1966) The noradrenaline content of the varicosities of sympathetic adrenergic nerve terminals in the rat. Acta Physiol Scand 67: 289–294PubMedCrossRefGoogle Scholar
  8. Demarest KT, Moore KE (1981) Type A monoamine oxidase catalyzes the intraneuronal deamination of dopamine within nigrostriatal, mesolim-bic, tuberoinfundibular and tuberohypophyseal neurons in the rat. J Neural Transm 52: 175–187PubMedCrossRefGoogle Scholar
  9. Demarest KT, Smith DJ, Azzaro AJ (1980) The presence of the type A form of monoamine oxidase within nigrostriatal dopamine-containing neurons. J Pharm Exp Ther 215: 461–468Google Scholar
  10. Duch DS, Bacchi CJ, Edelstein MP, Nichol CA (1984) Inhibitors of histamine metabolism in vitro and in vivo. Correlations with antitrypanosomal activity. Biochem Pharmacol 33: 1547–1553PubMedCrossRefGoogle Scholar
  11. Ferkany JW, Andree TH, Clarke DE, Enna SJ (1981) Neurochemical effects of kojic amine, a gabamimetic, and its interaction with benzylamine oxidase. Neuropharmacology 20: 1177–1182PubMedCrossRefGoogle Scholar
  12. Fowler CJ, Oreland L (1980) The effect of lipid-depletion on the kinetic properties of rat liver monoamine oxidase-B. J Pharm Pharmacol 32: 681– 688PubMedCrossRefGoogle Scholar
  13. Fowler CJ, Tipton KF (1982) Deamination of 5-hydroxytryptamine by both forms of monoamine oxidase by the rat brain. J Neurochem 38: 733– 736PubMedCrossRefGoogle Scholar
  14. Fowler CJ, Ross SB (1984) Selective inhibitors of monoamine oxidase A and B: biochemical, pharmacological and clinical properties. Med Res Rev 4: 323–358PubMedCrossRefGoogle Scholar
  15. Fowler CJ, Tipton KF (1984) On the substrate specificities of the two forms of monoamine oxidase. J Pharm Pharmacol 36: 111–115PubMedCrossRefGoogle Scholar
  16. Fuller RW, Hemrick-Luecke SK (1981) Elevation of epinephrine concentration in rat brain by LY 51641, a selective inhibitor of type A monoamine oxidase. Res Commun Chem Pathol 32: 207–221Google Scholar
  17. Fuller RW, Hemrick-Luecke SK, Perry KW (1981) Influence of harmaline on the ability of pargyline to alter catecholamine metabolism in rats. Biochem Pharmacol 30: 1295–1298PubMedCrossRefGoogle Scholar
  18. Garrick NA, Murphy DL (1980) Species differences in the deamination of dopamine and other substrates for monoamine oxidase in brain. Psy-chopharmacology 72: 27–33Google Scholar
  19. Garrick NA, Murphy DL (1982) Monoamine oxidase type A: Differences in selectivity towards 1-norepinephrine compared to serotonin. Biochem Pharmacol 31: 4061–4066PubMedCrossRefGoogle Scholar
  20. Garrick NA, Scheinin M, Chang WH, Linnoila M, Murphy DL (1984) Differential effects of clorgyline on catecholamine and indoleamine metabolites in the cerebrospinal fluid of rhesus monkeys. Biochem Pharmacol 33: 1423–1427PubMedCrossRefGoogle Scholar
  21. Garrick NA, Seppala T, Linnoila M, Murphy DL (1985 a) The effects of ami-flamine on cerebrospinal fluid amine metabolites in the rhesus monkey. Eur J Pharmacol 110: 1–9PubMedCrossRefGoogle Scholar
  22. Garrick NA, Seppala T, Linnoila M, Murphy DL (1985 b) Rhesus monkey cerebrospinal fluid amine metabolite changes following treatment with the reversible monoamine oxidase type-A inhibitor cimoxatone. Psy-chopharmacology 86: 265–269Google Scholar
  23. Glover V, Elsworth JD, Sandler M (1980) Dopamine oxidation and its inhibition by (–)deprenyl in man. J Neural Transm 16: 163–172Google Scholar
  24. Glover V, Sandler M, Owen F, Riley GJ (1977) Dopamine is monoamine oxidase B substrate in man. Nature 265: 80–81PubMedCrossRefGoogle Scholar
  25. Goridis C, Neff NH (1971) Monoamine oxidase in sympathetic nerves: a transmitter specific enzyme type. Br J Pharmacol 43: 814–818PubMedCrossRefPubMedCentralGoogle Scholar
  26. Green AR, Youdim MB (1975) Effect of monoamine oxidase inhibition by clorgyline, deprenyl or tranylcypromine on 5-HT concentration in rat brain and hyperactivity following subsequent tryptophan administration. Br J Pharmacol 55: 415–422PubMedCrossRefPubMedCentralGoogle Scholar
  27. Hayes BE, Ostrow PT, Clarke DE (1983) Benzylamine oxidase in normal and atherosclerotic human aortae. Exp Mol Pathol 38: 243–254PubMedCrossRefGoogle Scholar
  28. Hesterberg R, Sattler J, Lorenz W, Stahlknecht CD, Barth H, Crombach M, Weber D (1984) Histamine content, diamine oxidase activity and histamine methyl transferase activity in human tissues: fact or fictions? Agents Actions 14: 325–334PubMedCrossRefGoogle Scholar
  29. Houslay MD, Tipton KF (1974) A kinetic evaluation of monoamine oxidase activity in rat liver mitochondrial outer membranes. Biochem J 139: 645–652PubMedPubMedCentralGoogle Scholar
  30. Kapeller-Adler R (1970) Amine oxidases and methods for their study. Wiley-Interscience, New YorkGoogle Scholar
  31. Keane PE, Menager J, Strolin-Benedetti M (1981) The effect of monoamine oxidase A and B inhibitors on rat serum prolactin. Neuropharmacology 20: 1157–1162PubMedCrossRefGoogle Scholar
  32. Kinemuchi H, Wakui Y, Kamijo K (1980) Substrate selectivity of type A and type B monoamine oxidase in rat brain. J Neurochem 35: 109–115PubMedCrossRefGoogle Scholar
  33. Koda LY, Bloom FE (1977) A light and electron microscopic study of noradrenergic terminals in the rat dentate gyrus. Brain Res 120: 327– 335Google Scholar
  34. Koide Y, Koide N, Ross S, Saaf J, Wetterberg L (1981) Monoamine oxidase in human platelets. Kinetics and methodological aspects. Biochem Pharmacol 30: 2893–2900PubMedCrossRefGoogle Scholar
  35. Kung HC, Wilson AG (1979) Characterization of rat pulmonary monoamine oxidase. Life Sci 24: 425–432PubMedCrossRefGoogle Scholar
  36. Kusche J, Lorenz W, Stahlknecht CD, Friedrich A, Schmidt A, Boo K, Rei-chert G (1978) Diamine oxidase activity in gastric and duodenal mucosa of man and other mammals with special reference to the pyloric junction. Agents Actions 8: 366–371PubMedCrossRefGoogle Scholar
  37. Lassen JB, Squires RF (1977) Inhibition of both MAO-A and MAO-B required for the production of hypermotility in mice with the 5-HT uptake inhibitors chlorimipramine and femoxetine. Neuropharmacology 16: 485–488CrossRefGoogle Scholar
  38. Lewinsohn R (1984) Mammalian monoamine-oxidizing enzymes, with special reference to benzylamine oxidase in human tissues. Braz J Med Biol Res 17: 223–256PubMedGoogle Scholar
  39. Lewinsohn R, Bohm KH, Glover V, Sandler M (1978) A benzylamine oxidase distinct from monoamine oxidase B-widespread distribution in man and rat. Biochem Pharmacol 27: 1857–1863PubMedCrossRefGoogle Scholar
  40. Linnoila M, Karoum F, Potter WZ (1982) Effect of low-dose clorgyline on 24-hour monoamine excretion in patients with rapidly cycling bipolar affective disorder. Arch Gen Psychiat 39: 513–516PubMedCrossRefGoogle Scholar
  41. Maitre L, Waldmeier PC, Lauber J, Bieck P (1984) Urinary excretion of catecholamine metabolites, tyramine and phenylethylamine in human volunteers after prolonged treatment with CGP11305 A and tranylcypromine. In: Tipton KF, Dostert P, Strolin-Benedetti M (eds) Monoamine oxidase and disease. Academic Press, London, pp 117–126Google Scholar
  42. Major LF, Murphy DL, Lipper S, Gordon E (1979) Effects of clorgyline and pargyline on deaminated metabolites of norepinephrine, dopamine and serotonin in human cerebrospinal fluid. J Neurochem 32: 229–231PubMedCrossRefGoogle Scholar
  43. Mantle TJ, Houslay MD, Garrett NJ, Tipton KF (1976) 5-hydroxytryptamine is a substrate for both species of monoamine oxidase in beef heart mitochondria. J Pharm Pharmacol 28: 667–671PubMedCrossRefGoogle Scholar
  44. McEwen Jr CM (1965) Human plasma monoamine oxidase. I. Purification and identification. J Biol Chem 240: 2003–2010PubMedGoogle Scholar
  45. Mefford IN, Roth KA, Jurik SM, Collman V, Mclntire S (1985) Epinephrine accumulation in rat brain after chronic administration of pargyline and LY 51641–comparison with other brain amines. Brain Res 399: 342– 345Google Scholar
  46. Mehrabian ZB, Nalbandyan RM (1983) Benzylamine oxidase from brain microvessels. Febs Lett 164: 89–92PubMedCrossRefGoogle Scholar
  47. Morgan DM (1985) Polyamine oxidases. Biochem Soc Transact 13: 322–326Google Scholar
  48. O’Carroll AM (1984) The oxidation of noradrenaline by the two forms of human brain monoamine oxidase. In: Tipton KF, Dostert P, Strolin-Benedetti M (eds) Monoamine oxidase and disease. Academic Press, London, pp 593–594Google Scholar
  49. O’Carroll AM, Fowler CJ, Phillips JP, Tobbia I, Tipton KF (1983) The de-amination of dopamine by human brain monoamine oxidase. Specificity for the two enzyme forms in seven brain regions. Naunyn-Schmiedeberg’s Arch Pharmacol 322: 198–202CrossRefGoogle Scholar
  50. Oreland L, Fowler CJ, Carlsson A, Magnusson T (1980) Monoamine oxidase-A and -B activity in the rat brain after hemitransection. Life Sci 26: 139–146PubMedCrossRefGoogle Scholar
  51. Oreland JL, Arai Y, Stenstrom A, Fowler CJ (1983 a) Monoamine oxidase activity and localization in the brain and the activity in relation to psychiatric disorders. In: Beckmann H, Riederer P (eds) Monoamine oxidase and its selective inhibitors. Karger, Basel (Mod probl pharmaco-psychiat, vol 19, pp 246–254)Google Scholar
  52. Oreland JL, Arai Y, Stenstrom A (1983 b) The activity of deprenyl (selegiline) on intra- and extraneuronal dopamine oxidation. Acta Neurol Scand 95: 81–85CrossRefGoogle Scholar
  53. Ortmann R, Waldmeier PC, Radecke E, Felner A, Delini-Stula A (1980) The effects of 5-HT uptake- and MAO-inhibitors on L-5-HTP-induced excitation in rats. Naunyn-Schmiedeberg’s Arch Pharmacol 311: 185–192CrossRefGoogle Scholar
  54. Rafaelsen OJ, Christensen NJ, Gjerris A (1985) Adrenaline and MAO-inhibi-tion in CSF and brain. Acta Pharmacol Toxicol 56: 98–104CrossRefGoogle Scholar
  55. Roth JA, Eddy BJ (1980) Kinetic properties of membrane-bound and triton X-100-solubilized human brain monoamine oxidase. Arch Biochem Biophys 205: 260–266PubMedCrossRefGoogle Scholar
  56. Roth JA, Feor K (1978) Deamination of dopamine and its 3-O-methylated derivative by human brain monoamine oxidase. Biochem Pharmacol 27: 1606–1608PubMedCrossRefGoogle Scholar
  57. Sattler J, Hesterberg R, Lorenz W, Schmidt U, Crombach M, Stahlknecht CD (1985) Inhibition of human and canine diamine oxidase by drugs used in an intensive care unit: relevance for clinical side effects? Agents Actions 16: 91–94PubMedCrossRefGoogle Scholar
  58. Schoepp DD, Azzaro AJ (1981) Specificity of endogenous substrates for types A and B monoamine oxidase in rat striatum. J Neurochem 36: 2025–2031PubMedCrossRefGoogle Scholar
  59. Schoepp DD, Azzaro AJ (1982) Role of type A and type B monoamine oxidase in the metabolism of released [3H] dopamine from rat striatal slices. Biochem Pharmacol 31: 2961–2968PubMedCrossRefGoogle Scholar
  60. Schoepp DD, Azzaro AJ (1983) Effects of intrastriatal kainic acid injection on [3H] dopamine metabolism in rat striatal slices: Evidence for postsynaptic glial cell metabolism by both the type A and B forms of monoamine oxidase. J Neurochem 40: 1340–1348PubMedCrossRefGoogle Scholar
  61. Seiler N (1981) Amide-bond-forming reactions of polyamines. In: Morris DR, Marton LJ (eds) Polyamines in biology and medicine. Dekker, New York, pp 127–149Google Scholar
  62. Seiler N, Wiechmann M, Fischer HA, Werner G (1971) The incorporation of putrescine carbon into gamma-aminobutyric acid in rat liver and brain in vivo. Brain Res 28: 317–325CrossRefGoogle Scholar
  63. Shaff RE, Beaven MA (1976) Turnover and synthesis of diamine oxidase (DAO) in rat tissues. Studies with heparin and cycloheximide. Biochem Pharmacol 25: 1057–1062PubMedCrossRefGoogle Scholar
  64. Sourkes TL, Missala K (1981) Putrescine metabolism and the study of diamine oxidase activity in vivo. Agents Actions 11: 20–27PubMedCrossRefGoogle Scholar
  65. Squires R (1972) Multiple forms of monoamine oxidase in intact mitochondria as characterized by selective inhibitors and thermal stability: a comparison of eight mammalian species. In: Costa E, Sandler M (eds) Monoamine oxidases–new vistas. Raven Press, New York (Adv biochem psychopharmacol, vol 5, pp 355–370)Google Scholar
  66. Squires RF, Lassen JB (1974) Inhibition of both A and B forms of MAO required for production of characteristic behavioral syndrome in rats after L-tryptophan loading. J Pharmacol 5: 96–CL2Google Scholar
  67. Stenstrom A, Arai Y, Oreland L (1985) Intra- and extraneuronal mono-amineoxidase A and B activities after central axotomy (hemisection) on rats. J Neural Transm 61: 105–113PubMedCrossRefGoogle Scholar
  68. Stjarne L (1975) Basic mechanisms and local feedback control of secretion of noradrenergic and cholinergic neurotransmitters. In: Iversen LL, Iver-sen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 6. Plenum Press, New York, pp 179–233Google Scholar
  69. Strolin-Benedetti M, Boucher T, Carlsson A, Fowler CJ (1983) Intestinal metabolism of tyramine by both forms of monoamine oxidase in the rat. Biochem Pharmacol 32: 47–52CrossRefGoogle Scholar
  70. Student AK, Edwards DJ (1977) Subcellular localization of types A and B monoamine oxidase in rat brain. Biochem Pharmacol 26: 2337–2342PubMedCrossRefGoogle Scholar
  71. Suzuki O, Hattori H, Masakazu O, Katsumata Y (1980) Characteristics of monoamine oxidase in mitochondria isolated from chick brain, liver, kidney and heart. Biochem Pharmacol 29: 603–607PubMedCrossRefGoogle Scholar
  72. Suzuki O, Katsumata Y, Masakazu O (1982) Substrate specificity of type A and type B monoamine oxidase. In: Kamijo K, Usdin E, Nagatsu T (eds) Monoamine oxidase: basic and clinical frontiers. Excerpta Medica, Amsterdam, pp 74–86Google Scholar
  73. Suzuki O, Matsumoto T (1985) Normetanephrine and metanephrine oxidized by both types of monoamine oxidase. Experientia 41: 634–636PubMedCrossRefGoogle Scholar
  74. Tipton KF, Youdim MB, Spires IP (1972) Beef adrenal medulla monoamine oxidase. Biochem Pharmacol 21: 2197–2204PubMedCrossRefGoogle Scholar
  75. Tipton KF, Houslay MD, Garrett NJ (1973) Allotopic properties of human brain monoamine oxidase. Nature 246: 213–214Google Scholar
  76. Tipton KF, Fowler CJ, Houslay MD (1982) Specificities of the two forms of monoamine oxidase. In: Kamijo K, Usdin E, Nagatsu T (eds) Monoamine oxidase: basic and clinical frontiers. Excerpta Medica, Amsterdam, pp 87–99Google Scholar
  77. Urwyler S, Von Wartburg JP (1980) Studies on the subcellular localization of monoamine oxidase types A and B and its importance for the deamina-tion of dopamine in the rat brain. Biochem Pharmacol 29: 3067–3073PubMedCrossRefGoogle Scholar
  78. Van Der Krogt JA, Koot-Gronsveld E, Van Den Berg CJ (1983) Localization of rat striatal monoamine oxidase activities towards dopamine, serotonin and kynuramine by gradient centrifugation and nigro-striatal lesions. Life Sci 33: 615–623CrossRefGoogle Scholar
  79. Von Euler US (1972) Synthesis, uptake and storage of catecholamines in adrenergic nerves. The effects of drugs. In: Eichler O, Fark A, Herken H, Welch AD (eds) Handb exp pharmacol, vol 33. Springer, Berlin Heidelberg New York, pp 186–230Google Scholar
  80. Waldmeier PC, Antonin KH, Feldtrauer JJ, Grunenwald C, Paul E, Lauber J, Bieck P (1985) Urinary excretion of O-methylated catecholamines, tyramine, and phenylethylamine in human volunteers treated with tranylcypromine and CGP11305A. Eur J Clin Pharmacol 25: 361–368CrossRefGoogle Scholar
  81. Waldmeier PC, Delini-Stula A, Maitre L (1976) Preferential deamination of dopamine by an A type monoamine oxidase in rat brain. Naunyn-Schmiedeberg’s Arch Pharmacol 292: 9–14CrossRefGoogle Scholar
  82. White HL, Glassman AT (1977) Multiple binding sites of human brain and liver monoamine oxidase: substrate specificities, selective inhibitions, and attempts to separate enzyme forms. J Neurochem 29: 987–997PubMedCrossRefGoogle Scholar
  83. Wolf WA, Youdim MB, Kuhn DM (1985) Does brain 5-HIAA indicate serotonin release or monoamine oxidase activity? Eur J Pharmacol 109: 381– 387Google Scholar
  84. Yang HY, Neff NH (1974) The monoamine oxidases of brain: Selective inhibition with drugs and the consequences for the metabolism of the biogenic amines. J Pharmacol Exper Ther 189: 733–740Google Scholar
  85. Youdim MB (1983) In vivo noradrenaline is a substrate for rat brain monoamine oxidase A and B. Br J Pharmac 79: 477–480CrossRefGoogle Scholar
  86. Yu PH (1979) Effect of lipid depletion on type-A and type-B monoamine oxidase of rat heart and bovine liver mitochondria. In: Singer TP, Von Korff RW, Murphy DL (eds) Monoamine oxidase: Structure, function and altered functions. Academic Press, New York, pp 233–244Google Scholar
  87. Zeller EA (1963) Diamine oxidases. In: Boyer PD, Lardy H, Myrback K (eds) The enzymes, vol 8. Academic Press, New York, pp 313–335Google Scholar
  88. Zeller EA, Arora KL (1979) On the role of hydroxylic and N-methyl groups in the interaction of phenylethylamines with monoamine oxidase types A and B. In: Usdin E, Kopin FJ, Barchas JD (eds) Catecholamines: basic and clinical frontiers, vol 1. Pergamon, New York, pp 195–197CrossRefGoogle Scholar

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© Springer-Verlag/Wien 1987

Authors and Affiliations

  • P. C. Waldmeier
    • 1
  1. 1.Research Department, Pharmaceuticals DivisionCiba-Geigy Ltd.BasleSwitzerland

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