Plasma amine oxidases

Amine oxidases catalyze the oxidative deamination of both xenobiotic and biogenic amines, and thus have many critical biological functions. Two distinct classes differ in the nature of their prosthetic groups [1]. The flavin-(FAD flavin adenine dinucleotide)-dependent amine oxidases include monoamine oxidases (MAO A and B) and polyamine oxidases. Amine oxidases not containing FAD, the so-called semicarbazide-sensitive amine oxidases (SSAO), include both plasma amine oxidases and tissue amine oxidases. These contain quinonoid structures as redox cofactors that are derived from posttranslationally modified tyrosine or tryptophan side chains, topaoquinone frequently playing this role [2]. 

Examination of the Merrell Dow series of haloallylamines as inactivators of bovine plasma amine oxidase recently has been reported. The (E)- and (Z)-3-fluoroallylamines were more potent than the 3-bromo analogues. In addition, the Z-isomers were more potent than the E-isomers, in contrast to the result reported for inactivation of MAO [81]. 

In contrast to the substantial work with MAO, relatively little research has been reported on the mechanism of inhibition of copper-containing amine oxidases and SSAO by cyclopropylamines. Bovine plasma amine oxidase, equine plasma amine oxidase, Escherichia coii amine oxidase, and Arthrobacter globiformis amine oxidase were inhibited by frans-2-phenylcyclopropylamine (8a) and the mode of inhibition was shown by spectral and crystal structure analyses to be competitive and reversible [36,37,129],... 

Pig kidney diamine oxidase was inhibited by CuSO (for 49 % at 0.1 mM) and by the Cu complexes of lysine and tyrosine, but not by (Cu,Zn)-SOD Similar observations were made with purified bovine plasma amine oxidase There was only a weak... 

Plasma amine oxidase 886 Plasma antithrombin III 177 Plasma membrane 12, 379 Plasmalemma. See Plasma membrane Plasmalogens 383s, 384 Plasmids 5, 248249 ColEl 248 drug resistance 248 Plasmin 634 Plasminogen 634 Plasmodesmata 10... 

Nonblue. These include galactose oxidase (GO) and amine oxidases (e.g., plasma amine oxidase, diamine oxidase, lysyl oxidase), which produce dihydrogen peroxide by the two-electron reduction of 02 [33], For GO (stereospecific primary alcohol oxidation), spectroscopic studies by Whittaker [70,71] suggest that the two-electron oxidation carried out by a mononuclear copper center is aided by a stabilized ligand-protein radical (i.e., (L)Cu(I) + 02 —> (L +)Cu(lI) + H202), obviating the need to get to Cu(III) in the catalytic cycle. Protein x-ray structures [33,72] reveal a novel copper protein cofactor, which would seem... 

The 19F-NMR of bovine plasma amine oxidase [102] and A. coli amine oxidase [103] derivatized with fluorine-substituted hydrazines allowed estimation of the distance between the hydrazine and the active site Cu ion. The rather large distance that has been calculated precludes that the Cu ions are in the immediate... 

MSMA has also been shown to inactivate bovine plasma amine oxidase (BPAO).495... 

The Copper Site. In a crystal form of ECAO shown to contain catalytically-active protein (Parsons et al., 1995), the eopper is penta-coordinated in approximate square pyramidal eonfiguration by four basal (equatorial) ligands (His 524, His 526, His 689 and a water [We]) and an apical (axial) water (Wa). The presence of equatorial and axial waters had been first reported by Barker et al. (1979) from EPR, water proton relaxation and kinetic studies on pig plasma amine oxidase and the prediction of histidines and waters as the copper ligands came from EXAFS studies by Scott and Dooley (1985). The equatorial water (We) is labile and not always present. In the HP AO structure (Li et al., 1998) it is present in some, but not all, of the six independent subunits in the same erystal. A comprehensive discussion of the spectroscopic properties of the copper site in amine oxidases, including the exchange rates for the equatorial and axial waters, is given in the review by Knowles and Dooley (1994). 

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-... 

Stopped flow kinetic studies by Hartmann and Klinman (1991) on bovine serum amine oxidase and by Olsson et al. (1976) on pig plasma amine oxidase showed that the substrate Schiff-base has an absorbance maximum at 350nm. 

Farnum, M., Palcic, M., and Klinman, J. P., 1986, pH dependence of deuterium isotope effects and tritium exchange in the bovine plasma amine oxidase reaction a role for single base catalysis in amine oxidation and imine exchange. Biochemistry, 25 1898n 1904. 

Oi, S., Inamasu, M., and Yasunobu, K. T., 1970, Mechanistic studies on beef plasma amine oxidase. Biochemistry, 9 337883383. 

Olsson, B., Olsson, J., and Pettersson, G., 1976, Stopped flow spectrophotometric characterisation of enzyme reaction intermediates in the anaerobic reduction of pig plasma amine oxidase by amine substrate, Eur. J. Biochem. 71 3758382. 

Rius, F. X., Knowles, P. F., and Pettersson, G., 1984, The kinetics of ammonia release during the catalytic cycle of pig plasma amine oxidase, Biochem. J. 220 767n772. 

Scott, R. A., and Dooley, D. M., 1985, X-ray absorption spectroscopic studies of the copper sites in bovine plasma amine oxidase, J. Amer. Chem. Soc. 107 4348n4350. 

Yamada, H., Yasunobu, K., Yamano, T., and Mason, H. S., 1963, Copper in plasma amine oxidase, Nature 198 1092nl093. 

A number of enzymes which catalyze oxidation reactions, including mammalian lysyl and plasma amine oxidases and bacterial alcohol dehydrogenases, have been determined to utilize pyrroloquinoline quinone (PQQ, methoxatin) as a cofactor (Duine et al., 1987). Substrates of the amine oxidases appear to be activated for a-proton abstraction by formation of a Schiff base with PQQ, fol-... 

The results were further confirmed by resonance Raman spectrometry on comparing the spectra of phenylhydrazone and p-nitrophenylhydrazone of bovine plasma amine oxidase with the derivatized pentapeptides of the active site and the model compound. All these spectra showed great similarity in position (wavenumber) and spectral band intensity, while the spectrum of a PQQ model compound differed markedly [45]. Similar experiments confirmed the presence of topa quinone in porcine kidney, pea seedling and Arthrobacter PI amine oxidases. Moreover, the experimental data obtained for intact enzymes excluded the possibility of an artificial topa quinone formation during the proteolysis and peptide isolation [45]. 

Recently, the cofactor peptides have also been isolated from semicarbazide-sensitive amine oxidases purified from bovine and porcine aortas [52], sequenced and confirmed to contain the topa quinone. The same topa quinone consensus sequence was also found in the primary structures of amine oxidases from human kidney [53], human retina [54] and rat colon [55], so called amiloride-binding proteins , and amine oxidase from human placenta [56] that shows 81% identity with bovine plasma amine oxidase [57], bovine lung amine oxidase [58], and amine oxidases from pea and lentil seedlings [59,60], chick pea seedlings [61], and Arabidopsis thaliana [62] obtained by the molecular cloning of respective DNAs. 

Early studies performed with bovine plasma and porcine kidney amine oxidases have shown that the enzymes undergo irreversible inactivation upon reaction with several acetylenic substrates (propargylamine, 2-chloroallylamine and 2-butyne-1,4-diamine), which was diminished by substrate protection [118]. Other types of mechanism-based inactivators of bovine plasma amine oxidase are some glycine esters with relatively acidic a-protons. These esters are converted to ketenes, which may acylate the active site and inactivate the enzyme [119]. 

Plasma amine oxidases are in blood plasma of mammals and include spermine oxidase, which deaminates spermine and other polyamines. 

---