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At least 19 recordsLinked to original sources
PubMed1989

Monoamine oxidase, monoamine oxidase inhibitors, and panic disorder.

Monoamine oxidase inhibitors are effective in the treatment of panic attacks. Phenelzine has been used most often with good effect and is regarded by some as the treatment of first choice for panic disorders. Nevertheless the potential dangers of the use of non-specific MAOIs are well recognised and there is a need for safer drugs. The efficacy of specific MAO inhibitors such as moclobemide (MAO-A) and deprenyl (MAO-B) are yet to be investigated. The activity of the enzyme MAO in blood platelet (MAO-B) has been extensively studied. A review of early findings of elevated MAO activity suggests a number of reasons why the data should be interpreted with caution. Recent studies do not support the earlier findings and suggest no difference in platelet MAO activity between patients and controls. Similarly studies of the endogenous MAO inhibitor, tribulin, suggest that the output in panic disorder patients is similar to that of controls. Studies of the effectiveness of specific MAOIs in panic attacks are warranted as are further studies of the biochemical aetiology.

Fear↗
PubMed1977

Subcellular distribution of cytochrome c oxidase, monoamine oxidase and lactate dehydrogenase in the developing chick telencephalon.

The distribution of cytochrome c oxidase monoamine oxidase and lactate dehydrogenase, together with protein, after isopycnic centrifugation of a crude mitochondrial fraction of chick telencephalon homogenate in a linear sucrose density gradient, was followed during late embryogenesis and postnatal maturation. Two main populations of subcellular organelles differentiate; they were characterized biochemically and analyzed by electron microscopy. One population, with a progressively defined mean buoyant density of 1.170 g/ml, exhibited a high relative activity of monoamine oxidase, with a low and relatively constant cytochrome c oxidase/monoamine oxidase activity ratio. This population was composed of free mitochondria and mitochondria enclosed in nerve endings, and possibly of mitochondria of perikaryal and glial origin. A second population, with a progressively well defined mean buoyant density of 1.182-1.186 g/ml, exhibited a high relative activity of cytochrome c oxidase, with a high and increasing cytochrome c oxidase/monoamine oxidase activity ratio. The biochemical and functional significance of these results were discussed.

Animals↗
PubMed1998

Identification of an FAD superfamily containing protoporphyrinogen oxidases, monoamine oxidases, and phytoene desaturase. Expression and characterization of phytoene desaturase of Myxococcus xanthus.

A large number of FAD-containing proteins have previously been shown to contain a signature sequence that is referred to as the dinucleotide binding motif. Protoporphyrinogen oxidase (PPO), the penultimate enzyme of the heme biosynthetic pathway, is an FAD-containing protein that catalyzes the six electron oxidation of protoporphyrinogen IX. Sequence analysis demonstrates the presence of the dinucleotide binding motif at the amino-terminal end of the protein. Analysis of the current data base reveals that PPO has significant sequence similarities to mammalian monoamine oxidases (MAO) A and B, as well as to bacterial and plant phytoene desaturases (PHD). Previously MAOs have been shown to contain FAD, but there are no publications demonstrating the presence of FAD in purified PHDs. We have carried out the expression and purification of PHD from the bacterium Myxococcus xanthus and demonstrate the presence of noncovalently bound FAD. Sequence analysis demonstrate that PPO is closely related to bacterial PHDs and more distantly to plant PHDs and animal MAOs. Interestingly bacterial MAOs are no more closely related to PPOs, PHDs, and animal MAO's than they are to the unrelated Pseudomonas phenyl hydroxylase. All of the related sequences contain not only the basic putative dinucleotide binding motif that is found frequently for FAD-binding proteins, but they also have high similarity in an approximately 60-residue long region that extends beyond the dinucleotide motif. This region is not found among any other proteins in the current data base and, therefore, we propose that this region is a signature motif for a superfamily of FAD-containing enzymes that is comprised of PPOs, animal MAOs, and PHDs.

Amino Acid Sequence↗
PubMed1976

Effect of oral contraceptives on platelet monoamine oxidase, monoamine excretion, and adrenocortical function.

Studies with animals indicate that there are cyclical changes in the monoamine oxidase (MAO) activity of brain and uterus, and that these changes may be due to changes in estrogen and progesterone levels. To determine if oral contraceptives (OC) alter the tissue MAO activity of healthy women, we measured platelet MAO activity in 7 control women and in 7 women who were receiving combination estrogen-progesterone OC. The platelet MAO of the control women and the women receiving OC did not differ with the use of tryptamine and serotonin as MAO substrates. The two groups did not differ with respect to the following: serum serotonin, plasma tryptophan, plasma tyrosine, and the urinary excretion of tryptamine, tyramine, serotonin, 5-hydroxyindoleacetic acid, creatinine, 17-hydroxycorticosteroids, 17-ketosteroids, and urinary free cortisol. The subjects receiving OC had higher plasma cortisol concentrations than the controls. Two women in the seventh month of uncomplicated pregnancy, who underwent these studies, had higher plasma cortisol and urinary 17-ketosteroid excretion than control subjects. In the remaining tests the results of pregnant subjects did not differ from those of control subjects. We conclude that tissue MAO activity is not altered by OC or pregnancy.

Adrenal Cortex↗
PubMed1993

Effect of rapid eye movement sleep deprivation on rat brain monoamine oxidases.

Monoamine oxidase, monoamine oxidase-A, and monoamine oxidase-B activities were compared in free moving, rapid eye movement sleep-deprived, recovered, and control rat brains. The activities were estimated in the whole brain, cerebrum, cerebellum, whole brainstem, medulla, pons, and midbrain. The flowerpot method was used for continuing deprivation for one, two, or four days. Monoamine oxidase activity decreased significantly in the cerebrum and the cerebellum of the sleep-deprived rats, whereas monoamine oxidase-A and monoamine oxidase-B were differentially affected. Medullary MAO-A was the first to be affected, showing an increase after just one day of rapid eye movement sleep deprivation, while longer deprivation decreased its activity. The activity of monoamine oxidase-B was not significantly affected in any brain areas of the deprived rats until after two days of rapid eye movement sleep deprivation. All the altered enzyme activities returned to control levels after recovery. Control experiments suggest that the decrease was primarily caused by the rapid eye movement sleep deprivation and was not due to nonspecific effects. These findings are consistent with past studies and may help to explain earlier observations. The results support the involvement of aminergic mechanisms in rapid eye movement sleep. The plausible reasons for the changes in the activities of monoamine oxidases, after rapid eye movement sleep deprivation, are discussed.

Animals↗
PubMed2006

Substrate selectivity of monoamine oxidase A, monoamine oxidase B, diamine oxidase, and semicarbazide-sensitive amine oxidase in COS-1 expression systems.

The substrate selectivity of monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), diamine oxidase (DAO), and semicarbazide-sensitive amine oxidase (SSAO) was investigated in the absence of chemical inhibitors using the COS-1 cells expressed with respective amine oxidase. Serotonin (5-hydroxytryptamine), 1-methylhistamine, and histamine were preferentially oxidized by MAO-A, SSAO, and DAO, respectively, at a low substrate concentration. In contrast, benzylamine, tyramine, and beta-phenylethylamine served as substrates for all of MAO-A, MAO-B, and SSAO. Each amine oxidase showed broad substrate selectivity at a high substrate concentration. The cross-inhibition was remarkable in MAO-A and MAO-B, especially in MAO-A, but not in SSAO and DAO. A study of the substrate selectivity of amine oxidases should include consideration of the effects of substrate concentration and specific chemical inhibitors.

Amine Oxidase (Copper-Containing)↗
PubMed2005

R1, a novel repressor of the human monoamine oxidase A.

Monoamine oxidase catalyzes the oxidative deamination of a number of neurotransmitters. A deficiency in monoamine oxidase A results in aggressive behavior in both humans and mice. Studies on the regulation of monoamine oxidase A gene expression have shown that the Sp1 family is important for monoamine oxidase A expression. To search for novel transcription factors, the sequences of three Sp1 sites in the monoamine oxidase A core promoter were used in the yeast one-hybrid system to screen a human cDNA library. A novel repressor, R1 (RAM2), has been cloned. The R1 cDNA encodes a protein with 454 amino acids and an open reading frame at the 5'-end. The transfection of R1 in a human neuroblastoma cell line, SK-N-BE (2)-C, inhibited the monoamine oxidase A promoter and enzymatic activity. The degree of inhibition of monoamine oxidase A by R1 correlated with the level of R1 protein expression. R1 was also found to repress monoamine oxidase A promoter activity within a natural chromatin environment. A gel-shift assay indicated that the endogenous R1 protein in SK-N-BE (2)-C cells interacted with the R1 binding sequence. R1 also bound directly to the natural monoamine oxidase A promoter in vivo as shown by chromatin immunoprecipitation assay. Immunocytochemical analysis showed that R1 was expressed in both cytosol and nucleus, which suggested a role for R1 in transcriptional regulation. Northern blot analysis revealed the presence of endogenous R1 mRNA in human brain and peripheral tissues. Taken together, this study shows that R1 is a novel repressor that inhibits monoamine oxidase A gene expression.

Amino Acid Sequence↗
PubMed1986

Purification of human blood platelet monoamine oxidase.

Monoamine oxidase B has been purified from human blood platelets 185-fold to a specific activity of 113 nmole/min/mg protein by a combination of Triton X-100 solubilization and ion exchange chromatography. A protein fraction corresponding to 58,000 Da on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was identified as monoamine oxidase by its ability to bind [3H]Pargyline.

Blood Platelets↗
PubMed2002

Tyrosine residues near the FAD binding site are critical for FAD binding and for the maintenance of the stable and active conformation of rat monoamine oxidase A.

Monoamine oxidase is a flavin-containing enzyme located at the mitochondrial outer membrane that catalyzes the oxidative deamination of amines. To investigate the role of tyrosine residues near the FAD-binding site, Cys-406, of monoamine oxidase A, the tyrosine residues at posiyions 402, 407, and 410 were indurdually replaced with alanine or phenylalanine and the effects of the mutations on catalytic activity, FAD binding, and enzyme structure were examined. Half or fewer of the mutant proteins incorporated FAD. The mutation of Tyr-407 to alanine led to an almost completely loss of catalytic activity for serotonin, PEA, tyramine, and tryptamine. A substantial decrease in the catalytic activity was also observed with the enzymes mutated at Tyr-402 and Tyr-410 to alanine, although the effect of the latter mutation was much less. All these mutants were sensitive to trypsin treatment of the purified enzyme, while the wild type enzyme was resistant to treatment. On the other hand, substitution of Tyr-402 or Tyr-407 with phenylalanine had little effect on these properties. Taken together, we conclude that tyrosine residues near Cys-406 may be form a pocket to facilitates FAD incorporation, the catalytic center, and a stable conformation, probably through interactions among the aromatic rings of the tyrosine residues and FAD.

Amino Acid Sequence↗
PubMed1994

Kinetic properties of cloned human liver monoamine oxidase A.

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.

Amines↗
PubMed1993

Substrate-specific enhancement of the oxidative half-reaction of monoamine oxidase.

Monoamine oxidases A and B have identical flavin sites but different, although overlapping, amine substrate specificity. Reoxidation of ternary complexes containing substrate is much faster than of free enzyme, and the enhancement is greater in the A form than the B form. The oxidative half-reaction was studied with a variety of substrates to elucidate the specificity of the effect and to probe the different influences of substrate on the flavin reoxidation in the two forms of the enzyme. The second-order rate constant for the reoxidation was highest with monoamine oxidase A when kynuramine was the ligand (508 x 10(3) M-1 s-1) compared to 4 x 10(3) M-1 s-1 in its absence. MPTP (166 x 10(3) M-1 s-1) also enhanced reoxidation well, but indole substrates stimulated only poorly (e.g., tryptamine, 29 x 10(3) M-1 s-1; serotonin, 50 x 10(3) M-1 s-1). For the A form, the reduction of the flavin was rate-limiting in all cases. For the B form, reoxidation was rate-limiting for beta-phenylethylamine and contributed to the determination of the overall rate with several substrates. The ratio of the enhanced rate of oxidation to the rate of reduction correlated with the redox state of the enzyme in turnover experiments. All the observations are consistent with alternate paths of reoxidation, via either free enzyme or a reduced enzyme-substrate complex. The flux through each path is determined by the relative dissociation constants and rate constants.

Animals↗
PubMed2002

Inhibitors alter the spectrum and redox properties of monoamine oxidase A.

Monoamine oxidase A (MAO A) catalyses the oxidation of both neurotransmitter and ingested amines. The mechanism of catalysis involves the covalently bound FAD cofactor. Although substrates and inhibitors alter the thermodynamic and kinetic properties of the flavin, how the ligands interact with the flavin is unknown. This work characterises the spectral changes that occur on inhibitor binding to MAO A and examines how the binding influences the flavin. The inhibitors, D-amphetamine, harmine, tetrindole, and befloxatone all induce similar (but not identical) changes in the spectrum of MAO A, consistent with stacking of inhibitor with the flavin in the active site. D-Amphetamine, harmine, and tetrindole stabilise the semiquinone form of FAD during reduction of MAO A by dithionite and no further reduction of these inhibitor-MAO A complexes has been observed. In contrast, semiquinone is never observed during reduction of the befloxatone-MAO A complex. Instead, partial reduction directly to the FADH(2) form occurs extremely slowly. Thus, inhibitor binding has a strong, structure-dependent influence on the environment of the flavin that alters its electronic properties.

Carbazoles↗
PubMed1975

Characterization of pancreatic islet monoamine oxidase.

Monoamine oxidase (MAO) is present in isolated islets of Langerhans of rabbits, golden hamsters, and rats. Tryptamine, tyramine, serotonin, and dopamine can serve as substrates for this enzyme. We compared the properties of islet and liver MAO in the rabbit. The Michaelis constant (K(m)) for tryptamine of islet MAO (6.5 times 10-5M) is greater than the K(m) of liver MAO (3 times 10-5M). The K(m) for tyramine of islet MAO (1.5 times 10-4M) is similar to the K(m) of liver MAO (1.8 times 10-4M). Islet MAO appeared to be more susceptible to heat inactivation (50 degrees C) than did liver MAO. This may be an artifact produced by the collagenase technique used in the preparation of the islets, as collagenase treatment of liver increased the thermal lability of the MAO in this tissue. Liver and islet MAO have a comparable sensitivity to MAO inhibitors such as clorgyline, deprenyl, tranylcypromine, pargyline, and harmine. The present report, along with previous reports that MAO inhibitors alter insulin secretion, suggests that islet MAO may modify insulin secretion.

Animals↗
PubMed1988

Localization of distinct monoamine oxidase A and monoamine oxidase B cell populations in human brainstem.

Monoclonal antibodies, specific for either monoamine oxidases A or B, were used to determine the localization of monoamine oxidase in the human brain. Two distinct populations of neurons were detected by immunocytochemical staining. Neurons in regions rich in catecholamines were positive for monoamine oxidase A, including the nucleus locus coeruleus, the nucleus subcoeruleus and the medullary reticular formation. In these regions, monoamine oxidase A could be co-localized with the synthetic enzyme, dopamine-beta-hydroxylase. Neurons in the substantia nigra and the periventricular region of the hypothalamus, areas rich in dopamine neurons, stained for monoamine oxidase A but with much less frequency and intensity. The major accumulation of monoamine oxidase B-positive neurons was observed in the same regions in which monoamine oxidase B is found to co-localize with serotonin in monkey tissues, including the nucleus raphe dorsalis and the nucleus centralis superior. In addition, both monoamine oxidase A and B were localized in distinct populations of neurons in the lateral and tuberal regions of the hypothalamus, a region shown recently to contain histamine neurons in rats. Some glial cells were stained throughout the brain for monoamine oxidase A or B suggesting that glia are capable of either expression or uptake of these proteins.

Antibodies, Monoclonal↗
PubMed1985

Monoamine oxidase A and monoamine oxidase B activities are catalyzed by different proteins.

Monoamine oxidases A and B (amino: oxygen oxidoreductase (deaminating) (flavin-containing), EC 1.4.3.4) have been identified in the outer membranes of rat liver mitochondria by their covalent reaction with the inhibitor, [3H]pargyline. On analysis by polyacrylamide gel electrophoresis under denaturing conditions. Monoamine oxidase A was found to migrate more slowly that monoamine oxidase B. Proteins which correspond to monoamine oxidases A and B (as identified by the electrophoretic distribution of covalently bound [3H]pargyline) were excised from the gels. Subsequent analysis showed that both monoamine oxidase A and monoamine B had been highly purified by this procedure. Electrophoretic analysis of the peptides produced by limited proteolysis with bovine trypsin, alpha-chymotrypsin, Staphylococcus aureus V8 proteinase and cyanogen bromide indicate that monoamine oxidases A and B have different amino acid sequences.

Amino Acid Sequence↗
PubMed1989

[Neurochemical perspectives of the function of monoamine oxidases].

Monoamine oxidase (MAO) and its subtypes MAO-A and MAO-B show different distribution in post mortem human brain areas. While MAO-B is the predominant type in glial tissue, intraneuronal MAO is either of type A (locus coeruleus, only 10% of substantia nigra neurons stain MAO-A), while raphe neurons contain entirely MAO-B. Inhibition of MAO-subtypes leads to accumulation of biogenic amines in glial tissue while there is a selective intraneuronal influence differing between various brain areas. Generation of toxic end-products (eg. aldehydes, hydrogen peroxide, ammonia) may contribute to trigger or at least to progress Parkinson's disease.

Animals↗