Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the isolated cardiomyocytes of spontaneously hypertensive rats (SHR, 3 months old) MAO A and B activities were significantly increased compared to the myocytes in the hearts of age-matched Wistar-Kyoto rats. This increase was not associated with cardiac hypertrophy in these young animals, but might represent an early event in the development of hypertrophy. A semicarbazide-sensitive amine oxidase (SSAO) activity was found in cardiomyocytes. This activity showed a high affinity for benzylamine (Km 5-6 microM) and was not inhibited by 10(-4) M pargyline and 10(-5) M deprenyl, but was largely inhibited by 10(-4) M B24 (3,5-diethoxy-4-aminomethylpyridine), a specific inhibitor of semicarbazide-sensitive amino oxidase with high affinity for benzylamine. The SSAO enzyme of rat cardiomyocytes is a copper-amine oxidase and has a crossreactivity with the antibodies raised against pure pig plasma benzylamine oxidase. In the cardiomyocytes of 3-month old SHR rats the level of this enzymic activity is not significantly increased.
Biochem Mol Med 1997 Dec
PMID:Monoamine oxidase and semicarbazide-sensitive amine oxidase activities in isolated cardiomyocytes of spontaneously hypertensive rats. 944 72

The effect of alloxan-induced diabetes was studied on the activity of monoamine oxidase (MAO), the oxidative deaminating enzyme of monoamine neurotransmitters. MAO was assayed from discrete brain regions like medial preoptic area and median eminence--arcuate region of hypothalamus, septum, amygdala, thalamus, hippocampus, pons and medulla. In all these areas studied, the induction of diabetes resulted in significant increase in MAO activity at 3, 8, 15 and 28 day intervals, whereas, the treatment of diabetic rats with insulin led to recovery in the enzyme activity. Blood glucose levels increased significantly after induction of diabetes and the recovery was seen after insulin treatment. These data suggest the involvement of MAO in diabetes associated alterations in physiological and endocrinological disorders.
Mol Cell Biochem 1997 Dec
PMID:Effect of experimental diabetes on monoamine oxidase activity from discrete areas of rat brain: relationship with diabetes associated reproductive failure. 945 Jun 40

Abnormalities in monoamine oxidase (MAO) levels have been implicated in a wide range of psychiatric disorders. We have examined a VNTR polymorphism at the X-linked MAOA gene to test two hypotheses: (1) Do variants of the MAOA gene play a role in any of the behavioral disorders associated with Tourette syndrome or drug abuse? (2) If so, is there any correlation between the length of the alleles and the phenotypic effect? We examined two independent groups: 375 TS patients, relatives and controls, and 280 substance abusers and controls. The alleles were divided into four groups of increasing size. There was a significant association between the MAOA gene and behavioral phenotypes in both groups, and in both the longest alleles were associated with the greatest phenotypic effect. The strongest effect was for the diagnosis of drug dependence (P=0.00003). The VNTR allele groups were in significant linkage disequilibrium with the Fnu4H1 polymorphism previously shown to be associated with MAO-A activity. While these results are consistent with the possibility that different-sized alleles of the short-repeat polymorphisms themselves may play a role in gene regulation, further studies directly linking these alleles with enzyme levels need to be done.
Mol Psychiatry 1998 Jan
PMID:Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse. 949 13

An interesting flavoprotein-type monoamine oxidase (MAO) was recently isolated from Aspergillus niger and cloned [Schilling, B. & Lerch, K. (1995a) Biochim. Biophys. Acta 1243, 529-537; Schilling, B. & Lerch, K. (1995b) Mol. Gen. Genet. 247, 430-438]. The properties of this MAO, as well as a substantial part of its amino acid sequence, resemble those of both MAO A and B from higher animals, raising the possibility that it may be an evolutionary precursor of these mitochondrial enzymes. It differs from MAO A and B in several respects, however, including the fact that it is soluble and of peroxisomal location and that the FAD is non-covalently attached. We have overexpressed the fungal enzyme (MAO-N) in Escherichia coli and isolated it in pure form. Since several of the observations of previous workers on MAO-N could not be reproduced, we have reexamined its substrate specificity, interaction with reversible and irreversible inhibitors and other catalytic and molecular properties. MAO-N has a considerably higher turnover number on many aliphatic and aromatic amines than either form of the mammalian enzyme. Some aspects of the substrate specificity resemble those of MAO B, while others are similar to MAO A, including biphasic kinetics in double reciprocal plots. Contrary to a previous report [Schilling, B. & Lerch, K. (1995a) Biochim. Biophys. Acta 1243, 529-537], however, the fungal enzyme does not oxidize serotonin, norepinephrine, dopamine or other biogenic amines. MAO-N is irreversibly inhibited by stoichiometric amounts of both (-)deprenyl and clorgyline in a mechanism-based reaction, forming flavocyanine adducts with N5 of the FAD, like the mammalian enzymes, but inactivation is much faster with clorgyline than deprenyl, suggesting a closer resemblance to MAO A than B. The dissociation constants for a large number of reversible competitive inhibitors have been determined for MAO-N and comparison with similar values for MAO A and B again pointed to a greater similarity to the former than the latter.
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PMID:Isolation and characterization of an evolutionary precursor of human monoamine oxidases A and B. 957 86

The concentrations of ceruloplasmin could not be determined by comparing the oxidase activities toward p-phenylenediamine and o-dianisidine in rat whole serum with those of purified ceruloplasmin because of the different specific amine oxidase activities of ceruloplasmin purified from normal and gamma-irradiated rats and the lability caused by freezing and thawing. A competitive enzyme linked immunosorbent assay with antigens immobilized on the solid phase was developed to measure the ceruloplasmin in rat serum. The blocking materials and pH of the coating buffer had an effect on the amount of ceruloplasmin bound to the microtiter plates. The blocking materials nonspecifically reacted with the rabbit anti-rat ceruloplasmin IgG, and consequently the coating sensitivity was decreased and standard curves were not formed completely. Because rabbit anti-rat ceruloplasmin IgG did not show any cross reactivity with rat albumin and hemoglobin, these proteins did not affect the assay at a concentration of 200 micrograms/ml. This assay is useful for measuring the concentration of ceruloplasmin in normal and irradiated rat serum.
Biochem Mol Biol Int 1998 Jul
PMID:Development of a competitive enzyme linked immuno sorbent assay to measure ceruloplasmin in gamma-irradiated rat serum. 967 61

The D- and L-specific nicotine oxidases are flavoproteins involved in the oxidative degradation of nicotine by the Gram-positive soil bacterium Arthrobacter nicotinovorans. Their structural genes are located on a 160-kbp plasmid together with those of other nicotine-degrading enzymes. They are structurally unrelated at the DNA as well as at the protein level. Each of these oxidases possesses a high degree of substrate specificity; their catalytic stereoselectivity is absolute, although they are able to bind both enantiomeric substrates with a similar affinity. It appears that the existence of these enzymes is the result of convergent evolution. The amino acid sequence of 6-hydroxy-l-nicotine oxidase (EC 1.5.3.6) as derived from the respective structural gene shows considerable structural similarity with eukaryotic monoamine oxidases (EC 1.4.3.4) but not with monoamine oxidases from prokaryotic bacteria including those of the genus Arthrobacter. These similarities are not confined to the nucleotide-binding sites. A 100-amino acid stretch at the N-terminal regions of 6-hydroxy-l-nicotine oxidase and human monoamine oxidases A possess a 35% homology. Overall, 27.0, 26.9, and 25.8% of the amino acid positions of the monoamine oxidases of Aspergillus niger (N), humans (A), and rainbow trout (Salmo gairdneri) are identical to those of 6-hydroxy-l-nicotine oxidase (Smith-Waterman algorithm). In addition, the G+C content of the latter enzyme is in the range of that of eukaryotic monoamine oxidases and definitely lower than that of the A. nicotinovorans DNA and even that of the pAO1 DNA. The primary structure of 6-hydroxy-d-nicotine oxidase (EC 1.5.3.5) does not reveal its evolutionary history as easily. Significant similarities are found with a mitomycin radical oxidase from Streptomyces lavendulae (23.3%) and a "hypothetical protein" from Mycobacterium tuberculosis (26.0%). It is proposed that the plasmid-encoded gene of 6-hydroxy-l-nicotine oxidase evolved after horizontal transfer from an eukaryotic source.
J Mol Evol 1999 Feb
PMID:Horizontal gene transfer involved in the convergent evolution of the plasmid-encoded enantioselective 6-hydroxynicotine oxidases. 992 86

Kinetic properties of novel amine oxidase isolated from sainfoin (Onobrychis viciifolia) were compared to those of typical plant amine oxidase (EC 1.4.3.6) from lentil (Lens culinaris). The amine oxidase from sainfoin was active toward substrates, such as 1,5-diaminopentane (cadaverine) with K(m) of 0.09 mM and 1,4-diaminobutane (putrescine) with K(m) of 0.24 mM. The maximum rate of oxidation for cadaverine at saturating concentration was 2.7 fold higher than that of putrescine. The amine oxidase from lentil had the maximum rate for putrescine comparable to the rate of sainfoin amine oxidase with the same substrate. Both amine oxidases, like other plant Cu-amine oxidases, were inhibited by substrate analogs (1,5-diamino-3-pentanone, 1,4-diamino-2-butanone and aminoguanidine), Cu2+ chelating agents (diethyltriamine, 1,10-phenanthroline, 8-hydroxyquinoline, 2,2'-bipyridyl, imidazole, sodium cyanide and sodium azide), some alkaloids (L-lobeline and cinchonine), some lathyrogens (beta-aminopropionitrile and aminoacetonitrile) and other inhibitors (benzamide oxime, acetone oxime, hydroxylamine and pargyline). Tested by Ouchterlony's double diffusion in agarose gel, polyclonal antibodies against the amine oxidase from sainfoin, pea and grass pea cross-reacted with amine oxidases from several other Fabaceae and from barley (Hordeum vulgare) of Poaceae, while amine oxidase from the filamentous fungus Aspergillus niger did not cross-react at all. However, using Western blotting after SDS-PAGE with rabbit polyclonal antibodies against the amine oxidase from Aspergillus niger, some degree of similarity of plant amine oxidases from sainfoin, pea, field pea, grass pea, fenugreek, common melilot, white sweetclover and Vicia panonica with the A. niger amine oxidase was confirmed.
Biochem Mol Biol Int 1999 Jan
PMID:Comparison of kinetic properties of amine oxidases from sainfoin and lentil and immunochemical characterization of copper/quinoprotein amine oxidases. 1009 44

1. Many drugs used to treat psychiatric disorders contain a chiral center or a center of unsaturation and are marketed as a mixture of the resultant enantiomers or geometric isomers, respectively. These enantiomers or geometric isomers may differ markedly with regard to their pharmacodynamic and/or pharmacokinetic properties. 2. Examples of the effects of chiral centers or geometric centers on such properties are given for drugs from the following classes: antidepressants (tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, viloxazine, bupropion, trazodone, mianserin, venlaflaxine); benzodiazepines, zoplicone, and antipsychotics. 3. As described in this review, there are several notable examples of psychiatric drugs currently available where the individual enantiomers or geometric isomers differ considerably with regard to factors such as effects on amine transport systems, interactions with receptors and metabolizing enzymes, and clearance rates from the body. Indeed, relatively recent developments in analytical and preparative resolution of racemic and geometric drug mixtures and increased interest in developing new drugs which interact with specific targets, which have been described in detail at the molecular level, have resulted in increased emphasis on stereochemistry in drug development.
Cell Mol Neurobiol 1999 Jun
PMID:Chirality and drugs used in psychiatry: nice to know or need to know? 1031 92

1. The principal routes of metabolism of the following monoamine oxidase inhibitors (MAOIs) are described: phenelzine, tranylcypromine, pargyline, deprenyl, moclobemide, and brofaromine. 2. Acetylation of phenelzine appears to be a minor metabolic pathway. Phenelzine is a substrate as well as an inhibitor of MAO, and major identified metabolites of phenelzine include phenylacetic acid and p-hydroxyphenylacetic acid. Phenelzine also elevates brain GABA levels, and as yet unidentified metabolites of phenelzine may be responsible for this effect. beta-Phenylethylamine is a metabolite of phenelzine, and there is indirect evidence that phenelzine may also be ring-hydroxylated and N-methylated. 3. Tranylcypromine is ring-hydroxylated and N-acetylated. There is considerable debate about whether or not it is metabolized to amphetamine, with most of studies in the literature indicating that this does not occur. 4. Pargyline and R(-)-deprenyl, both propargylamines, are N-demethylated and N-depropargylated to yield arylalkylamines (benzylamine, N-methylbenzylamine, and N-propargylbenzylamine in the case of pargyline and amphetamine, N-methylamphetamine and N-propargylamphetamine in the case of deprenyl). These metabolites may then undergo further metabolism, e.g., hydroxylation. 5. Moclobemide is biotransformed by C- and N-oxidation on the morpholine ring and by aromatic hydroxylation. An active metabolite of brofaromine is formed by O-demethylation. It has been proposed that another as yet unidentified active metabolite may also be formed in vivo. 6. Preliminary results indicate that several of the MAOIs mentioned above are substrates and/or inhibitors of various cytochrome P450 (CYP) enzymes, which may result in pharmacokinetic interactions with some coadministered drugs.
Cell Mol Neurobiol 1999 Jun
PMID:Metabolism of monoamine oxidase inhibitors. 1031 94

1. We studied the effect of isolation stress in 3- and 12-month-old rats individually housed in metabolic cages for 7 days. Urine (24 hr) was collected daily from one group of animals of each age. The other group was tested in an open field and on a hot plate on days 1 and 7. 2. Total deambulation in the open-field test was lower in young than in older rats both on day 1 (54.7 +/- 9.9 vs 80 +/- 8.9 crossings/session; P < 0.04) and on day 7 (21 +/- 9 vs 48 +/- 7 crossings per session; P < 0.04) and decreased significantly in the two groups when tested on day 7 (P < 0.03). Latency to paw-licking in the hot-plate test was longer in young than in older animals on day 1 (14 +/- 2 vs 8 +/- 4 sec; P < 0.05) but was similar in the two groups on day 7. 3. Urinary excretions of norepinephrine (NE) and epinephrine (E) were determined by HPLC with electrochemical detection. Urinary NE in day 1 was similar in young and older animals (2627 +/- 828 vs 3069 +/- 598 ng/24 hr). In young animals NE excretion decreased along the study and was significantly (P < 0.02) lower than on day 1 during the last 3 days of the study. Conversely, in older animals urinary excretion of NE remained similar throughout the study. On day 7 urinary excretion of NE in older animals was about two fold that in young rats. Urinary E was similar in young and older rats (341 +/- 127 vs 532 +/- 256 ng/24 hr) on day 1 and showed a tendency to increase throughout the study. 4. Urinary monoamine oxidase inhibitory (IMAO) activity was determined by testing the ability of urine extracts to inhibit rat liver MAO activity in vitro and was higher in young than in older animals throughout the study (day 1, 54.8 +/- 4.2 vs 25.1 +/- 5.1%; P < 0.02). In young rats excretion of IMAO was significantly higher during the last 3 days of the study than on day 1 (P < 0.05). In older animals urinary IMAO showed a tendency to increase at the end of the study. 5. Isolation stress caused by housing rats in metabolic cages results in different behavioral and metabolic responses in young and older animals. Young animals exhibit a lower locomotor and analgesic response and excrete lower amounts of NE and higher IMAO activity in the urine than older rats. The metabolic and behavioral responses to isolation stress are highly dependent on the age of the animals tested. These results should be taken into consideration when designing experiments requiring the use of metabolic cages.
Cell Mol Neurobiol 1999 Oct
PMID:Influence of age on stress responses to metabolic cage housing in rats. 1038 60


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