Top

Published in:

01-06-2013 | Translational Neurosciences - Original Article

Do MAO A and MAO B utilize the same mechanism for the C–H bond cleavage step in catalysis? Evidence suggesting differing mechanisms

Authors: R. Orru, M. Aldeco, D. E. Edmondson

Published in: Journal of Neural Transmission | Issue 6/2013

Abstract

The detailed molecular mechanism proposed for the MAO-catalyzed oxidation of amines has been controversial with the basic assumption that both MAO A and MAO B follow the same pathway for the C–H bond cleavage step. Using the mechanistic approach of investigation of electronic effects of various benzylamine ring substituents in experiments at pH 9.0, human MAO A exhibits a kinetic behavior characteristic of an H⁺ abstraction, while human MAO B exhibits kinetic properties characteristic of a H⁻ abstraction. These results lead to the conclusion that the assumption that MAO A and MAO B follow identical mechanisms is incorrect.

Aldeco M, Arslan BK, Edmondson DE (2011) Catalytic and inhibitor binding properties ofzebrafish monoamine oxidase (zMAO): comparisons with human MAO A and MAO B. Comp Biochem Physiol B 59:78–83CrossRef

Bondi A (1964) Van der Waals volumes and radii. J Phys Chem 68:441–451CrossRef

Copeland RA (2000) Enzymes: a practical introduction to structure, mechanism, and data analysis, 2nd edn. Wiley, New york

Dubey R, Kothari S, Banerji KK (2002) Kinetics and mechanism of the oxidation ofsubstituted benzylamines by hexamethylenetetramine-bromine. J Phys Org Chem 15:103–107CrossRef

Dunn RV, Marshall KR, Munro AW, Scrutton NS (2008) The pH dependence of kineticisotope effects in monoamine oxidase indicates stabilization of the neutral amine in theenzyme-substrate complex. FEBS J 275:3850–3858PubMedCrossRef

Edmondson DE, Binda C, Wang J, Upadhyay A, Mattevi A (2009) Molecular and mechanistic properties of the membrane-bound mitochondrial monoamine oxidases. Biochemistry 48:4230–4430

Fitzpatrick PA (2010) Oxidation of amines by flavoproteins. Arch Biochem Biophys 493:13–25PubMedCrossRef

Hansch C, Leo A, Hoekman D (1995) Exploring QSAR: hydrophobic, electronic, and stericconstants. American Chemical Society, Washington

Jones TZE, Balsa D, Unzeta M, Ramsay RR (2007) Variations in activity and inhibitionwith pH: the protonated amine is the substrate for monoamine oxidase, but unchargedinhibitors bind better. J Neural Transm 114:707–712PubMedCrossRef

Li M, Hubálek F, Newton-Vinson P, Edmondson DE (2002) High-level expression of humanliver monoamine oxidase A in Pichia pastoris: comparison with the enzyme expressed in Saccharomyces cervisiae. Protein Expr Purif 24:152–162PubMedCrossRef

Lu X, Rodriguez M, Ji H, Silverman R, Vintem APB, Ramsay RR (2002) Irreversibleinactivation of mitochondrial monoamine oxidases. In: Chapman S, Perham R, Scrutton N (eds) Flavins and flavoproteins. Agency For Scientific Publications, Berlin, pp 817–830

MacMillar S, Edmondson DE, Matsson O (2011) Nitrogen kinetic isotope effects for themonoamine oxidase catalyzed oxidation of benzylamine and (1,1–2H2) benzylamine: nitrogen rehybridization and CH bond cleavage are not concerted. J Am Chem Soc 133:12319–12321PubMedCrossRef

Milczek EM, Binda C, Rovida S, Mattevi A, Edmondson DE (2011) The gating residuesIle199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitorrecognition. FEBS J 278:4860–4869PubMedCrossRef

Miller JR, Edmondson DE (1999) Structure-activity relationships in the oxidation of para-substituted benzylamine analogues by recombinant human liver monoamine oxidase A. Biochemistry 38:13670–13683PubMedCrossRef

Newton-Vinson P, Hubálek F, Edmondson DE (2000) High level expression of human livermonoamine oxidase B in Pichia pastoris. Protien Expr Purif 20:334–345CrossRef

Shukla R, Sharma PK, Kotai L, Banerji K (2003) Kinetics and mechanism of the oxidationof substituted benzylamines by cetylmethylammonium permanganate. Proc. Indian Acad Sci Chem Sci 115:129–134CrossRef

Walker MC, Edmondson DE (1994) Structure-activity relationships in the oxidation ofbenzylamine analogues by bovine liver mitochondrial monoamine oxidase B. Biochemistry 33:7088–7098PubMedCrossRef

Wang J, Edmondson DE (2011) ²H Kinetic isotope effects and pH dependence of catalysis asmechanistic probes of rat monoamine oxidase A: comparisons with the human enzyme. Biochemistry 50:7710–7717PubMedCrossRef

Title: Do MAO A and MAO B utilize the same mechanism for the C–H bond cleavage step in catalysis? Evidence suggesting differing mechanisms
Authors: R. Orru
M. Aldeco
D. E. Edmondson
Publication date: 01-06-2013
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 6/2013
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-013-0991-3

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Do MAO A and MAO B utilize the same mechanism for the C–H bond cleavage step in catalysis? Evidence suggesting differing mechanisms

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2013

Computational modeling of the direct hydride transfer mechanism for the MAO catalyzed oxidation of phenethylamine and benzylamine: ONIOM (QM/QM) calculations

Special Issue: 15th amine oxidase conference: re-examine the amines

New tools for studying old questions: antibodies for human diamine oxidase

Characterization of diamine oxidase from human seminal plasma

Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model

Cellular localization and trafficking of vascular adhesion protein-1 as revealed by an N-terminal GFP fusion protein