Amine oxidases catalytic mechanism

M. Mure, S.A. Mills, J.P. Klinman, Catalytic mechanism of the topa quinone containing copper amine oxidases. Biochemistry 41 (2002) 9269-9278. 

C.G. Saysell, W.S. Tambyrajah, J.M. Murray, C.M. Wilmot, S.E.V. Philips, M.J. McPherson, P.F. Knowles, Probing the catalytic mechanism of Escherichia coli amine oxidase using mutational variants and a reversible inhibitor as a substrate analogue, Biochem. J. 365 (2002) 809-816. 

Mechanisms. Studies of model reactions473-476 and of electronic, Raman,456 477 478 ESR,479/480 and NMR spectra and kinetics481 have contributed to an understanding of these enzymes.459 461 464 482 483 For these copper amine oxidases the experimental evidence suggests an aminotransferase mechanism.450 453 474 4743 d Tire structure of the E.coli oxidase shows that a single copper ion is bound by three histidine imidazoles and is located adjacent to the TPQ (Eq. 15-53). Asp 383 is a conserved residue that may be the catalytic base in Eq. 15-53.474b A similar mechanism can be invoked for LTQ and TTQ. 

Topaquinone (TPQ), the oxidized form of 2,4,5-trihydroxyphenylalanine (TOPA), is the cofactor of copper-containing amine oxidases. The following model compounds have been prepared in order to understand the catalytic function of TPQ the jV-pivaloyl derivative of 6-hydroxydopamine in aqueous acetonitrile [38] topaquinone hydantoin and a series of 2-hydroxy-5-alkyl-l,4-benzoquinones in anhydrous acetonitrile (o- as well as />-quinones) [39] 2-hydroxy-5-methy 1-1,4-benzoquinone in aqueous system [40] and 2,5-dihydroxy-1,4-benzoquinone [41]. Reaction of model compounds with 3-pyrrolines revealed why copper-quinopro-tein amine oxidases cannot oxidize a secondary N [42], The studies clearly showed that certain model compounds do not require the presence of Cu for benzylamine oxidation whereas TPQ does [38,40] the aminotransferase mechanism proceeds via the -quinone form [39] the 470 nm band can be ascribed to a 71-71 transition of TPQ in />-quinonic form with the C-4 hydroxyl ionized but hydrogen bonded to some residue [40] hydrazines attack at the C-5 carbonyl, forming an adduct in the azo form [41], Electrochemical characterization has been carried out for free TPQ [43],... 

Cu has a bifunctional role in copper-quinoprotein amine oxidases, catalyzing the formation of TPQ from the specific tyrosy l residue in the precursor protein and playing a role in the catalytic mechanism, most probably with 02 reacting with Cu(I) in the oxidative part of the cycle. The recent discovery of LTQ suggests that other combinations of quinone cofactors may be found in the future. 

The catalytic mechanism of amine oxidases can be fonnally divided into reductive and oxidative half cycles... 

The catalytic mechanism for amine oxidases is shown in Figure 13. Pioneering kinetic studies by Pettersson and coworkers during the 1970s on pig plasma amine oxidase (Pettersson, 1985) indicated that Schiff-... 

With galactose oxidase, our understanding of the catalytic mechanism is less advanced than for amine oxidases but all the essential foundations for continued advances are in place high resolution X-ray structures of native and mutational variant forms, eomplete with advanced spectroscopic... 

A. S., Palcic, M. A., Knowles, P. F., McPherson, M. J., and Phillips, S. E. V., 1997, The catalytic mechanism of die quinoenzyme amine oxidase from Escherichia coli exploring the reductive half reaction. Biochemistry 36 1608fil620. 

The crystal stmctures of snbstrate-rednced amine oxidases have been solved, along with site-directed mutants, metal-snbstitnted forms, enzyme complexes with inhibitors, the Oi mimic nitric oxide (NQ) and peroxide. These have been correlated with a wealth of biochemical and spectroscopic data that form the basis for the catalytic mechanism proposed in Scheme 8. A Schiffbase complex species (b) is formed between snbstrate amine and TPQ C-5. Base-catalyzed proton abstraction from substrate a-methylene group, via the conserved active-site aspartate residue, yields the reduced cofactor in a product Schiff-base complex, species (c). Hydrolysis releases product aldehyde, leaving the cofactor in the reduced aminoquinol form, species (d). 

DuBois JL, Klinman JP. Mechanism of post-translational quinone formation in copper amine oxidases and its relationship to the catalytic turnover. Arch. Biochem. Biophys. 2005 433 255-265. 

The postulated catalytic mechanism of amine oxidases starts from the qui-none form of the cofactor (Fig. 17). The distal oxygen atom is replaced by an amino group in a transamination reaction. The amine is then re-oxidized by molecular oxygen to the original quinone. The copper ion is not involved directly in catalysis but is only a cofactor in the synthesis of TOPA quinone (Fig. 18). 

Fig. (3). Mechanism of the substrate oxidation by copper amine oxidases [29]. The scheme shows the roles of copper, topa quinone cofactor and proton abstracting base (Asp) in the catalytic cycle. The oxidized enzyme (a) reacts with an amine substrate giving a Schiff base formation at C-5 of the TPQ (b-c), followed by proton abstraction (d). After hydrolysis and release of the aldehyde, an aminoresorcinol species is formed (e), and the reduced cofactor is reoxidized by molecular oxygen via Cu(I)-semiquinone intermediate (/).

Among the topics covered in the supplement is an historical overview about the knowledge of the biochemistiy of Monoamine Oxidase with speculations about future prospects, a review of the present knowledge about the catalytic properties of Monoamine Oxidase, reviews of the biochemistry and pharma-cology of the semicarbazide-sensiti ve Amine Oxidases and of the endogenous substrates both for Monoamine Oxidase and other Amine Oxidases. Reviews of the mechanism of action for the... 

Monoamine oxidase, which exists in two distinct forms, referred to as MAO A and MAO B, is one of the enzymes responsible for the degradation of biologically important amines. Compounds that block the catalytic action of MAO A, which is selective for the degradation of norepinephrine and serotinin, have antidepressant effects whereas compounds that inhibit MAO B, which degrades dopamine in the brain, are useful for treating Parkinson s disease [190, 191]. Both MAO A and MAO B contain flavin co-enzyme attached at the 8-a-position to an enzyme-active cysteine residue (54). A one-electron transfer mechanism (Scheme 15) for the oxidations catalyzed by MAO was first proposed by Silverman [192] and Krantz [193,194]. 

Cross-linking contributes to tissue strength and limits the need for fiber replacement, but it also inhibits repair following a mechanical injury or infection (Sect. 8.1.3.). Lysyl oxidase catalysis is self-limiting to avoid excessive cross-linking. The oxidation rate of lysine amine residues is limited to approximately 100 catalytic turnovers per enzyme molecule because ammonia and other reaction by-products inactivate it irreversibly. 

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