Skip to main content

The deamination of dopamine by human brain monoamine oxidase

Specificity for the two enzyme forms in seven brain regions

Summary

The deamination of dopamine has been studied in seven regions of human brain. Both A and B forms of the enzyme were found to be active towards this substrate. The ratio of activities of MAO-A: MAO-B was found to vary considerably from brain region to brain region, from about 1∶1 for the cerebral and cerebellar cortex to about 1∶2 for the pons and medula oblongata. Enzyme titration studies and comparisons of the substrate specificities of MAO-A and MAO-B across the brain indicated that dopamine was metabolised by the same MAO active centres as other monoamines. In the cerebral cortex, the K m values of MAO-A and-B towards dopamine were found to be 210 and 230 μM, respectively, indicating that the relative contributions of these two forms towards the oxidation of this substrate will not be significantly affected by changes in its concentration.

This is a preview of subscription content, access via your institution.

References

  • Collins GGS, Sandler M, Williams ED, Youdim MBH (1970) Multiple forms of human brain mitochondrial monoamine oxidase. Nature (Lond) 225:817–820

    Google Scholar 

  • Fowler CJ, Oreland L (1981) Substrate- and stereoselective inhibition of human brain monoamine oxidase by 4-dimethylamino-α,2-dimethylphenethylamine (FLA 336). J Pharm Pharmacol 33:403–406

    Google Scholar 

  • Fowler CJ, Tipton KF (1982) Deamination of 5-hydroxytryptamine by both forms of monoamine oxidase in the rat brain. J Neurochem 38:733–736

    Google Scholar 

  • Fowler CJ, Callingham BA, Mantle TJ, Tipton KF (1978) Monoamine oxidase A and B: a useful concept? Biochem Pharmacol 27: 97–101

    Google Scholar 

  • Fowler CJ, Callingham BA, O'Connor MDL, Matthews EK (1980a) The effect of sonication upon monoamine oxidase-A and-B in the rat liver. Biochem Pharmacol 29:1185–1188

    Google Scholar 

  • Fowler CJ, Oreland L, Marcusson J, Winblad B (1980b) Titration of human brain monoamine oxidase-A and-B by clorgyline and l-deprenyl. Naunyn-Schmiedeberg's Arch Pharmacol 311:263–272

    Google Scholar 

  • Fowler CJ, Wiberg Å, Oreland L, Winblad B (1980c) Titration of human brain type B monoamine oxidase. Neurochem Res 6:697–708

    Google Scholar 

  • Fowler CJ, Wiberg Å, Oreland L, Marcusson J, Winblad B (1980d) The effect of age on the activity and molecular properties of human brain monoamine oxidase. J Neural Transm 49:1–20

    Google Scholar 

  • Garrick NA, Murphy DL (1981) Differences in the preferential deamination of l-norepinephrine, dopamine and serotonin by MAO in rodent and primate brains. In: Usdin E, Weiner N, Youdim MBH (eds) Function and regulation of monoamine enzymes. Basic and clinical aspects. Macmillan, London, pp 517–525

    Google Scholar 

  • Glover V, Elsworth JD, Sandler M (1980) Dopamine oxidation and its inhibition by (-)-deprenyl in man. J Neural Transm Suppl 16: 163–172

    Google Scholar 

  • Glover V, Sandler M, Owen F, Riley GJ (1977) Dopamine is a monoamine oxidase B substrate in man. Nature (Lond) 265:80–81

    Google Scholar 

  • Green AR, Mitchell BD, Tordoff AFC, Youdim MBH (1977) Evidence for dopamine deamination by both type A and type B monoamine oxidase in rat brain in vivo and for the degree of inhibition of enzyme necessary for increased functional activity of dopamine and 5-hydroxytryptamine. Br J Pharmacol 60:343–349

    Google Scholar 

  • Hall DWR, Logan BW, Parsons GH (1969) Further studies on the inhibition of monoamine oxidase by M & B 9302 (clorgyline). I. Substrate specificity in various mammalian species. Biochem Pharmacol 18:1447–1454

    Google Scholar 

  • Houslay MD, Tipton KF (1973) The nature of the electrophoretically separable multiple forms of rat liver monoamine oxidase. Biochem J 135:173–186

    Google Scholar 

  • Houslay MD, Tipton KF (1974) A kinetic evaluation of monoamine oxidase activity in rat liver mitochondrial outer membranes. Biochem J 139:645–652

    Google Scholar 

  • Johnston JP (1968) Some observations on a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 17:1285–1297

    Google Scholar 

  • Kinemuchi H, Wakui Y, Kamijo K (1980) Substrate selectivity of type A and type B monoamine oxidase in rat brain. J Neurochem 35:109–115

    Google Scholar 

  • Knoll J, Magyar K (1972) Some puzzling pharmacological effects of monoamine oxidase inhibition. Adv Biochem Psychopharmacol 5: 393–408

    Google Scholar 

  • MacKay AVP, Davies P, Dewar AJ, Yates CM (1978) Regional distribution of enzymes associated with neurotransmission by monoamines, acetylcholine and GABA in the human brain. J Neurochem 30: 827–839

    Google Scholar 

  • Markwell MAK, Haas SM, Bieber LL, Tolbert NE (1978) A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Analyt Biochem 87:206–210

    Google Scholar 

  • Oreland L, Arai Y, Stenstrom A (1982) MAO in post-mortem brains of psychiatric patients. In: Beckmann H, Riederer P (eds) Monoamine oxidase and its selective inhibitors: New concepts in therapy and research. Karger, Basel (in press)

    Google Scholar 

  • Otsuka S, Kobayashi Y (1964) A radioisotopic assay for monoamine oxidase determinations in human plasma. Biochem Pharmacol 13: 995–1006

    Google Scholar 

  • Owen F, Cross AJ, Lofthouse R, Glover V (1979) Distribution and inhibition characteristics of human brain monoamine oxidase. Biochem Pharmacol 28:1077–1080

    Google Scholar 

  • Riederer P, Reynolds GP, Youdim MBH (1981) Selectivity of MAO inhibition in human brain and their clinical consequences. In: Youdim MBH, Paykel ES (eds) Monoamine oxidase inhibitors — The state of the act. John Wiley, Chichester, pp 63–76

    Google Scholar 

  • Robinson DS (1975) Changes in monoamine oxidase and monoamines with human development and aging. Fed Proc 34:103–107

    Google Scholar 

  • Roth JA (1976) Evidence for a single catalytic binding site on human brain type B monoamine oxidase. J Neurochem 27:1107–1112

    Google Scholar 

  • Roth JA, Feor K (1978) Deamination of dopamine and its 3-O-methylated derivative by human brain monoamine oxidase. Biochem Pharmacol 27:1606–1608

    Google Scholar 

  • Suzuki O, Katsumata Y, Oya M (1981a) Oxidation of α-phenethylamine by both types of monoamine oxidase: examination of enzymes in brain and liver mitochondria of eight species. J Neurochem 36:1298–1301

    Google Scholar 

  • Suzuki O, Katsumata Y, Oya M (1981b) Characterisation of eight biogenic indoleamines as substrates for type A and type B monoamine oxidase. Biochem Pharmacol 30:1353–1358

    Google Scholar 

  • Tipton KF, Houslay MD, Garrett NJ (1973) Allotopic properties of human brain monoamine oxidase. Nature New Biol (Lond) 246:213–214

    Google Scholar 

  • 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 87–99

    Google Scholar 

  • Waldmeier, PC, Maitre L (1975) Lack of significance of MAO-B for the in vivo deamination of dopamine. Naunyn-Schmiedeberg's Arch Pharmacol 287:R2-R3

    Google Scholar 

  • White HL, Glassman AT (1977) Multiple binding sites of human brain and liver monoamine oxidase: substrate specificities, selective inhibitors, and attempts to separate enzyme forms. J Neurochem 29: 987–997

    Google Scholar 

  • White HL, Tansik RL (1979) Characterization of multiple substrate binding sites of MAO. In: Singer TP, Von Korff RW, Murphy DL (eds) Monoamine oxidase; structure, function and altered functions. Academic Press, New York, pp 129–144

    Google Scholar 

  • Youdim MBH, Holman B (1975) The nature of inhibition of cat brain mitochondrial monoamine oxidase by clorgyline. J Neural Transm 37:11–24

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

O'Carroll, AM., Fowler, C.J., Phillips, J.P. et al. The deamination of dopamine by human brain monoamine oxidase. Naunyn-Schmiedeberg's Arch. Pharmacol. 322, 198–202 (1983). https://doi.org/10.1007/BF00500765

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00500765

Key words

  • Human brain
  • Dopamine
  • Monoamine oxidase
  • Clorgyline
  • Deprenyl