Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MONOAMINE OXIDASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1984

Saturated amines and diamines as substrates which inhibit beef liver mitochondrial monoamine oxidase.

Monoamines and diamines of 8-12 carbon atoms initially serve as substrates for purified beef liver monoamine oxidase but then lead to inhibition. The inhibition is not solely the result of aldehyde formation as addition of decylaldehyde does not inhibit benzylamine oxidation. Furthermore, neither the addition of alcohol dehydrogenase and NADH nor of semicarbazide prevent the inhibition of diaminodecane oxidation. The formation of a Schiff base on the enzyme surface resulting in aggregation or occlusion of the enzyme may be a cause of the inhibition. When concentrated enzyme solutions (greater than or equal to 1 mg/ml) are reduced by long-chain amines, 100% O2 causes only partial return of the flavin peak at 450 nm while enzyme activity continues to decrease. Substantial recovery of activity occurs (over a 3-4 week period) when inhibited enzyme is sedimented and resuspended in fresh buffer. These observations are discussed and compared with inhibition observed by other investigators with the substrate phenylethylamine.

Amines↗
PubMed2004

Structure and mechanism of monoamine oxidase.

Monoamine oxidases A and B (MAO A and MAO B) are mitochondrial outer membrane-bound flavoproteins that catalyze the oxidative deamination of neurotransmitters and biogenic amines. A number of mechanism-based inhibitors (MAOI's) have been developed for clinical use as antidepressants and as neuroprotective drugs. To facilitate the development of more effective and specific inhibitors, a detailed understanding of the structures and catalytic mechanisms of these enzymes is required. The recent development of high level expression systems for producing recombinant human liver MAO A and MAO B in Pichia pastoris has facilitated the determination of the three dimensional crystal structures of MAO B (up to 1.7 angstroms resolution) in complex with different reversible (isatin, 1,4-diphenyl-2-butene) and irreversible inhibitors (pargyline, N-(2-aminoethyl)-p-chlorobenzamide, and trans-2-phenylcyclopropylamine). The binding of substrates or inhibitors to MAO B involves an initial negotiation of a protein loop occurring near the surface of the membrane and two hydrophobic cavities; an "entrance" cavity and an "active site" cavity. These two cavities can either be separate or in a fused state depending on the conformation of the Ile199 side chain, which appears to function as a gate. The amine function of the bound substrate approaches the re face of the bent and "puckered" covalent FAD through an "aromatic cage" formed by two tyrosine residues that are perpendicular to the plane of the flavin ring. No amino acid residues that could function as acids or bases are found near the catalytic site. The existing structural data on MAO B support previous QSAR results and are also supportive of a proposed polar nucleophilic mechanism for MAO A and B catalysis rather than the alternatively proposed single electron transfer mechanism.

Amino Acid Sequence↗
PubMed1999

Structure-activity relationships in the oxidation of para-substituted benzylamine analogues by recombinant human liver monoamine oxidase A.

Monoamine oxidase A (MAO A) plays a central role in the oxidation of amine neurotransmitters. To investigate the structure and mechanism of this enzyme, recombinant human liver MAO A was expressed and purified from Saccharomyces cerevisiae. Anaerobic titrations of the enzyme require only 1 mol of substrate per mole of enzyme-bound flavin for complete reduction. This demonstrates that only one redox-active group (i.e., the covalent FAD cofactor) is involved in catalysis. The reaction rates and binding affinities of 17 para-substituted benzylamine analogues with purified MAO A were determined by steady state and stopped flow kinetic experiments. For each substrate analogue that was tested, the rates of steady state turnover (k(cat)) and anaerobic flavin reduction (k(red)) are similar in value. Deuterium kinetic isotope effects on k(cat), k(red), k(cat)/K(m), and k(red)/K(s) with alpha, alpha-[(2)H]benzylamines are similar for each substrate analogue that was tested and range in value from 6 to 13, indicating that alpha-C-H bond cleavage is rate-limiting in catalysis. Substrate analogue dissociation constants determined from reductive half-reaction experiments as well as from steady state kinetic isotope effect data [Klinman, J. P., and Matthews, R. G. (1985) J. Am. Chem. Soc. 107, 1058-1060] are in excellent agreement. Quantitative structure-activity relationship (QSAR) analysis of dissociation constants shows that the binding of para-substituted benzylamine analogues to MAO A is best correlated with the van der Waals volume of the substituent, with larger substituents binding most tightly. The rate of para-substituted benzylamine analogue oxidation and/or substrate analogue-dependent flavin reduction is best correlated with substituent electronic effects (sigma). Separation of the electronic substituent parameter (sigma) into field-inductive and resonance effects provides a more comprehensive treatment of the electronic correlations. The positive correlation of rate with sigma (rho approximately 2.0) suggests negative charge development at the benzyl carbon position occurs and supports proton abstraction as the mode of alpha-C-H bond cleavage. These results are discussed in terms of several mechanisms proposed for MAO catalysis and with previous structure-activity studies published with bovine liver MAO B [Walker, M. C., and Edmondson, D. E. (1994) Biochemistry 33, 7088-7098].

Anaerobiosis↗
PubMed1982

Characteristics and specificity of phenelzine and benserazide as inhibitors of benzylamine oxidase and monoamine oxidase.

The selectivity of benserazide and phenelzine toward inhibition of benzylamine oxidase (BzAO) and monoamine oxidases (MAO-A and MAO-B) was studied in homogenates of rat skull and lung. In addition, the kinetic interaction and reversibility of BzAO inhibition were assessed. Both drugs inhibited BzAO but only phenelzine inhibited MAO, whether tested in vitro or in vivo. Neither compound acted as an irreversible inhibitor of BzAO. Benserazide was found to be a noncompetitive inhibitor. Phenelzine acted as a substrate for BzAO followed by product-induced noncompetitive inhibition which was labile at 37 degrees but not at 4 degrees. A reversible component in phenelzine-induced inhibition of MAO-A and -B is also suggested from in vivo studies.

Animals↗
PubMed1993

Rapid and simultaneous determination of monoamine oxidase A and monoamine oxidase B activities in mouse brain homogenates by liquid chromatography with electrochemical detection.

Sensitive and rapid enzymatic assays have been developed and optimized to measure the separate and combined activities of monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in mouse brain tissue homogenates using liquid chromatography with electrochemical detection (LCEC). The selectivity for the two isozymes is primarily afforded by use of selective substrates, 5-hydroxytryptamine (5-HT) for MAO-A and 3-methoxy-4-hydroxybenzylamine (MHBA) for MAO-B. The selectivity of the separate assays is further enhanced by the use of inhibitors, deprenyl to block MAO-B and clorgyline to block MAO-A. The dual assay procedure, which employs no inhibitors, shows remarkably enhanced selectivity for each of the isozymes through the use of the two substrates; the preferred substrate for one isozyme acts as an effective competitive inhibitor of the nontargeted substrate for that isozyme, leading to substantially decreased activity for the latter substrate. Using the dual assay, kinetic constants determined for MAO-A (mean +/- SD) were: Km,5-HT = 39 +/- 7 microM, Vmax,5-HT = 37.6 +/- 2.1 pmol/mg wet tissue/min, Km,MHBA = 341 +/- 75 microM, and Vmax,MHBA = 27.7 +/- 2.3 pmol/mg wet tissue/min; those for MAO-B were: Km,MHBA = 108 +/- 11 microM, Vmax,MHBA = 44.3 +/- 1.2 pmol/mg wet tissue/min, Km,5-HT = 1704 +/- 122 microM, and Vmax,5-HT = 12.0 +/- 0.3 pmol/mg wet tissue/min. The separate isozyme procedures, when used without selective inhibitors, reflect only 88.3% of the MAO-A activity using the 5-HT velocity and only 66.0% of the MAO-B activity using the MHBA velocity. On the other hand, when the dual assay is employed, 98% of the observed 5-HT velocity can be directly attributed to MAO-A, and 94% of the observed MHBA velocity can be directly attributed to MAO-B. The dual assay was employed to demonstrate the relative change in the activity of these two enzymes in whole mouse brain between 27 and 74 days of age. During this time, the MAO-B activity increased from approximately 40 to approximately 60% of the total MAO activity. Under typical conditions, results can be easily obtained from any of the three procedures outlined for 100 samples in less than 2 working days, including only 3.5 h for the LCEC portion.

Animals↗
PubMed1975

Changes in monoamine oxidase and monoamines with human development and aging.

A series of studies of monoamines and their metabolism in a variety of human tissues indicate that there are aging effects that may alter neurotransmitter substances. Monoamine oxidase (MAO) activity has a significant positive correlation with age in plasma and blood platelets of normal subjects and patients suffering from depressive disorders. Monoamine oxidase and age correlate positively in hindbrain and in eight separate ares of human brains from patients who died from a variety of causes. Hindbrain norepinephrine concentration progressively decreases with advancing age (r equals -0.44, P less than 0.01) while no changes were noted for serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). Hindbrain norepinephrine concentration has a significant negative correlation with MAO (r equals -0.41, P less than 0.025) and hindbrain 5-HIAA has a significant positive correlation with MAO (r equals +0.66, P equals less than 0.05). These studies suggest that aging processes may significantly affect monoamine mechanisms and be a predisposing factor to the development of clinical diseases in man such as depression, parkinsonism and other disorders of central nervous system homeostasis.

Adult↗
PubMed1995

Further studies on the ex-vivo effects of procarbazine and monomethylhydrazine on rat semicarbazide-sensitive amine oxidase and monoamine oxidase activities.

Following administration of the anticancer agent, procarbazine, or one of its metabolites, monomethylhydrazine, to rats, activities of monoamine oxidases A and B (MAO A and MAO B) and of semicarbazide-sensitive amine oxidase (SSAO) were measured ex-vivo. Both compounds were found to be potent inhibitors of SSAO in tissue homogenates, exhibiting ID50 values in most tissues of approximately 8 mg kg-1 (procarbazine) and 0.08 mg kg-1 (monomethylhydrazine). Concurrent dose-dependent inhibition of MAO activities did not occur. However, in liver, potentiation of MAO B activity, to 140% of that in controls, was apparent following monomethyl-hydrazine and this effect was independent of the drug dose. Both compounds produced a dose-dependent potentiation of MAO A in brown adipose tissue, the elevation being more pronounced following monomethylhydrazine, with activity rising to 350% of that in control homogenates. In a parallel in-vitro study, monomethylhydrazine was without effect on MAO A in brown adipose tissue homogenates. By perfusing the SSAO substrate, benzylamine, through the isolated mesenteric arterial bed of the rat, it was found that pretreatment of animals with procarbazine or monomethylhydrazine reduced metabolism of this amine by a similar degree as had been determined ex-vivo in blood vessel homogenates. The results presented suggest that these compounds would be suitable for use as selective inhibitors in pharmacological examinations of SSAO function in isolated tissues and organs.

Amine Oxidase (Copper-Containing)↗
PubMed1983

Effect of ovariectomy and estrogen treatment on uterine benzylamine oxidase and monoamine oxidase type A.

The activity of monoamine oxidase type A (MAO-A) of rat uteri is known to be modulated by sex steroids but no information is available with regard to benzylamine oxidase (BzAO). Thus, uterine MAO-A and BzAO activities were assayed in ovariectomized (3 weeks) and ovariectomized plus estrogen treated rats (17 beta-estradiol, 10 micrograms/kg/day, i.p. for three days). Compared with sham operated controls, MAO-A activity (total and specific) was decreased by ovariectomy and restored partially by estrogen treatment. In contrast, BzAO activity was not influenced selectively. Total BzAO activity followed changes in uterine weight such that the specific activity of BzAO, per mg tissue, was not statistically different between the three experimental groups. Although changes in the specific activity of BzAO were found on a protein and DNA basis, these changes reflect primarily alterations in protein and DNA contents and not BzAO activity. Since BzAO appears to be insensitive to direct modulation by sex steroids and may be located predominantly in uterine blood vessels, it is speculated that the enzyme may serve as a marker for hormonal influences on the vascularity and structure of the uterine vascular bed.

Animals↗
PubMed1991

Ultrastructural localization of cytochrome oxidase and monoamine oxidase on microcylinders, a Long-Evans rat-specific mitochondrial inclusion.

The presence of a unique inclusion body, the microcylinder, in the intracristal space of mitochondria was previously reported in various types of cells from spotted rats of the Long-Evans strain, but was not found in cells of albino rats. The microcylinder is about 30 nm in diameter and of indefinite length, and is composed of six filamentous subunits surrounding a central one. We performed electron microscopic cytochemical studies on the cells of uriniferous tubules and the corpus striatum in normal spotted rats of the Long-Evans strain and albino rats of Wistar and Sprague-Dawley strains. On the basis of oxidative polymerization of 3, 3'-diaminobenzidine by cytochrome oxidase (CYO) an cupric ferrocyanide deposition by monoamine oxidase (MAO), microcylinders were demonstrated to exhibit activity of these enzymes. Reaction products of other mitochondrial enzymes, such as succinate dehydrogenase and lactate dehydrogenase, were not deposited on microcylinders. We conclude that microcylinders are rat strain-specific mitochondrial inclusions and consist of protein components, particularly containing the mitochondrial enzymes CYO and MAO.

Animals↗
PubMed1979

The role of plasma amine oxidase, platelet monoamine oxidase, and red cell catechol-O-methyl transferase in severe behavioral reactions to disulfiram.

The authors assayed platelet monoamine oxidase (MAO), plasma amine oxidase (AO), and red cell catechol-O-methyl transferase (COMT) in 32 male alcoholics before they began disulfiram treatment. Seven subjects developed psychotic reactions to disulfiram; these 7 had significantly lower pretreatment MAO and AO levels and significantly higher COMT than the patients who had no adverse reactions to disulfiram, which suggests that severe behavioral reactions to disulfiram are associated with differences in enzyme activities.

Adolescent↗
PubMed1991

[Phenolic constituents of licorice. IV. Correlation of phenolic constituents and licorice specimens from various sources, and inhibitory effects of licorice extracts on xanthine oxidase and monoamine oxidase].

The roots and/or rhizomes of Glychyrrhiza uralensis, G. glabra and G. inflata, and commercial licorice specimens from various regions or countries were analyzed by high-performance liquid chromatography (HPLC), and classified into three types based on their phenolic constituents. i) Type A: The roots and rhizomes of G. uralensis, commercial licorice specimens from northwestern region of China (Seihoku-kanzo) and from northeastern region of China (Tohoku-kanzo) in Japanese markets, and also several licorice specimens from Chinese markets. They contain licopyranocoumarin (6), glycycoumarin (7) and/or licocoumarone (8), which were not found in G. glabra and G. inflata. ii) Type B: The root and rhizome of G. glabra, and the licorice specimens imported from the Soviet Union and Afghanistan. They contain glabridin (9) and glabrene (10), which were not found in the samples of the other two Glycyrrhiza species. A root sample of Glycyrrhiza species from Turkey also contains 9 and 10. iii) Type C: The root sample of G. inflata. They contain licochalcones A (11) and B (12), which were not found in the samples of the other two Glycyrrhiza species. Commercial licorice specimens obtained in Japan, which were imported from Sinkiang of China (Shinkyo-kanzo), and some licorice specimens obtained from Chinese markets, have also been found to contain 11 and 12. The phenolics 6-12, characteristic constituents of types A, B or C, were not found in a specimen of cortex-free licorice from a Japanese market (kawasari-kanzo). Extracts of some licorice specimens of types A and B, and all of the licorice specimens of type C inhibited 40-56% of the xanthine oxidase activity at the concentration of 30 micrograms/ml. Extracts of some licorice specimens of types A and B also showed inhibitory effects on monoamine oxidase (44-64% inhibition, at the concentration of 30 micrograms/ml), which were slightly weaker than that of harmane hydrochloride.

Chromatography, High Pressure Liquid↗
PubMed1978

[Multiplicity of monoamine oxidase: inhibition of mitochondrial monoamine oxidase activity by isopropylhydrazide of D,L-serine].

Isopropylhydrazide of D,L-serine (IHS) inhibits by 50% (at 37 degrees for 10 min) deamination of serotonin or beta-phenylethylamine by monoamine oxidases from bovine brain stem mitochondrial membranes at the 2.6 X X 10(-5) M or 9 X 10(-5) M, respectively. In order to inhibit by 50% the deamination of tyramine under the same conditions a considerably lower (2.5 X X 10(-6) M) concentration of IHS is required. Kinetic studies of inhibition of enzymatic deamination of all the three biogenic monoamines by IHS showed that the irreversible blocking of the monoamine oxidase activity is preceeded by formation of dissociating enzyme-inhibitor complexes. Values of the dissociation constants of these complexes measured (at 37 degrees) with serotonin, phenylethylamine or tyramine as substrates for estimation of the residual monoamine oxidase activity are 0.47; 0.13 or 0.023 mM, respectively. Significant differences are also found between thermodynamic and activation parameters characterizing both both steps of interaction between IHS and the monoamine oxidases of mitochondrial membranes in the experiments with serotonin, phenylethylamine or tyramine as substrates. The data obtained suggest the existence of different monoamine oxidases (or their active sites) catalyzing oxidative deamination of serotonin, phenylethylamine or tyramine in the fragments of mitochondrial membranes from bovine brain stem.

Animals↗
PubMed1994

Semicarbazide-sensitive amine oxidase and monoamine oxidase in rat brain microvessels, meninges, retina and eye sclera.

Monoamine oxidase-A and -B (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) activities were assessed in several rat micro-vascular tissues and eyes using selective substrates and inhibitors. In rat brain microvessels both MAO-A and MAO-B activities are relatively high and the levels of the two types of MAO's are comparable. Retina possesses a similar ratio of MAO-A and B but the activities are much lower. Eye sclera and meninges exhibit mainly MAO-A and MAO-B, respectively. Aorta is the only tissue where SSAO is the predominant amine oxidase. Relatively low, but significant amounts of SSAO were also detected in brain microvessels, meninges, retina and eye sclera. Methylamine was observed to be deaminated by SSAO from different tissues. The physiological and toxicological implications of amine oxidases in these tissues are discussed.

Amine Oxidase (Copper-Containing)↗