Summary
Monoamine oxidases deaminate many amines, including neurotransmitters, by oxidation followed by spontaneous breakdown of the imine product. The reduced enzyme is reoxidized slowly by oxygen, but in the presence of amines, the rate of reoxidation is markedly enhanced. The extent of enhancement depends on the amine substrate, kynuramine enhancing the rate 125-fold, but 5-hydroxytryptamine only 6-fold. Here we describe the properties of human liver monoamine oxidase A which has been cloned into and overexpressed in yeast. The purified enzyme has a higher Km for oxygen than does the placental enzyme, but the steady-state parameters for the endogenous amines are the same. Tertiary amines are oxidized at slightly different rates by the two enzymes. The consequences of the branched pathway mechanism with substrate-dependent enhancement of reoxidation for the steady-state levels of the various enzyme species is discussed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bachurin SO, Sablin SO, Grishina GV, Gaydorova EL, Dubova LG, Zubor ND (1989) Kinetics of biotransformation of physiologically active 1-methyl-4-aryl-l,2,3,6-tetrahydropyridines by monoamines oxidase. Bioorganicheskaya khimia (russ) 15: 620–626.
Husain M, Edmondson DE, Singer TP (1982) Kinetic studies on the catalytic mechanism of liver monoamine oxidase. Biochemistry 21: 595–600.
Pearce LB, Roth JA (1985) Human brain monoamine oxidase type B: mechanism of deamination as probed by steady-state methods. Biochemistry 24: 1821–1826.
Ramsay RR, Koerber SC, Singer TP (1987) Stopped-flow studies on the mechanism of oxidation of N-methyl-4-phenyltetrahydropyridine by bovine liver monoamine oxidase B. Biochemistry 26: 3045–3050.
Ramsay RR (1991) Kinetic mechanism of monoamine oxidase A. Biochemistry 30: 4624–4629.
Singer TP (1991) Monoamine oxidases. In: Müller F (ed) Chemistry and biochemistry of flavoenzymes, vol 2. CRC Press, Boca Raton, pp 437–470.
Tan AK, Ramsay RR (1993) Substrate-specific enhancement of the oxidative half-reaction of monoamine oxidase. Biochemistry 32: 2137–2143.
Tan AK, Weyler W, Salach JI, Singer TP (1991) Differences in substrate specificities of monoamine oxidase A from human liver and placenta. Biochem Biophys Res Comm 181: 1084–1088.
Weyler W, Hsu Y-PP, Breakefield XO (1990a) Biochemistry and genetics of monoamine oxidase. Pharmacol Ther 47: 391–417.
Weyler W, Titlow CT, Salach JI (1990b) Catalytically active monoamine oxidase type A from human liver expressed in Saccharomyces cerevisiae contains covalent FAD. Biochem Biophys Res Commun 173: 1205–1211.
Weyler W, Salach JI (1985) Purification and properties of mitochondrial monoamine oxidase Type A from human placenta. J Biol Chem 260: 13199–13207.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer-Verlag
About this paper
Cite this paper
Ramsay, R.R., Tan, A.K., Weyler, W. (1994). Kinetic properties of cloned human liver monoamine oxidase A. In: Tipton, K.F., Youdim, M.B.H., Barwell, C.J., Callingham, B.A., Lyles, G.A. (eds) Amine Oxidases: Function and Dysfunction. Journal of Neural Transmission, vol 41. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9324-2_2
Download citation
DOI: https://doi.org/10.1007/978-3-7091-9324-2_2
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-82521-1
Online ISBN: 978-3-7091-9324-2
eBook Packages: Springer Book Archive