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

The activities of monoamine oxidase (MAO), responsible for oxidative deamination of many biogenic amines, and Na+, K(+)-ATPase, which plays a crucial role in the release mechanism of neurotransmitters, were determined in rat brain after acute starvation. They were assayed biochemically from four different regions of the brain in two subcellular fractions. Acute starvation decreased the activity of MAO, whereas the Na+,K(+)-ATPase activity was increased. An effect of starvation was also seen on the blood glucose level, body wt, and the protein content of different brain regions. Starvation or normal dietary fluctuations of certain nutrients that exert precursor influence over neurotransmitter synthesis are important to the brain, and contribute to its regulation of both neuroendocrine response and behavior. A rise in the substrate level, i.e., ATP, as a result of increased utilization of ketone bodies and low level of monoamines in the brain after acute starvation, may be the underlying factor for increasing the activity of Na+,K(+)-ATPase in rat brain. These results suggest that, probably, certain adaptive mechanisms become operative in the brain under disturbed physiological conditions.
Mol Chem Neuropathol 1990 Dec
PMID:Effect of acute starvation on monoamine oxidase and Na+,K(+)-ATPase activity in rat brain. 196 2

The novel reversible and selective inhibitor of monoamine oxidase-A (MAO-A) Ro 41-1049 [N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide HCl] shows inhibition characteristics similar to those of the structurally related reversible MAO-B inhibitors Ro 16-6491 and Ro 19-6327. In the present study, tritiated Ro 41-1049 was used as a high affinity ligand to study the binding characteristics of this inhibitor to MAO-A and its interactions with the enzyme. An homogeneous population of high affinity binding sites for [3H]Ro 41-1049 was found in membrane preparations from human frontal cortex and placenta (Kd = 16.5 +/- 1.4 and 64.4 +/- 19.2 nM, respectively). In frontal cortex the Bmax value for [3H]Ro 41-1049 (2.6 +/- 0.4 pmol/mg of protein) was about one third of the Bmax calculated for the MAO-B-selective ligand [3H]Ro 16-6491. The density of [3H]Ro 41-1049 binding sites in human placenta varied greatly in the different tissue samples investigated, showing an average Bmax of 101.7 +/- 36.5 pmol/mg of protein. Apparent binding equilibrium was reached after 1 hr of incubation at 37 degrees. At this temperature the binding was reversible, with a dissociation t 1/2 of about 35 min. At lower temperatures the radioactivity dissociation was much slower. Among the various drugs tested, only inhibitors of MAO-A were able to effectively prevent [3H]Ro 41-1049 specific binding. As previously reported for the MAO-B ligands [3H]Ro 16-6491 and [3H]Ro 19-6327, the analysis of the membrane-bound radioactivity showed that [3H]Ro 41-1049 was entirely recovered in the form of its aldehyde derivative, indicating that Ro 41-1049 was deaminated by MAO-A. The existence of a Ro 41-1049 adduct reversibly bound to the enzyme active site might explain the inhibition mechanism of this compound. The exposure of the radioligand-enzyme complex to NaBH3CN at pH 4.5 caused the irreversible covalent incorporation of about 70% of the specifically bound radioactivity into a 60-kDa polypeptide. This incorporation was dependent on the pH and on the amount of NaBH3CN added. The presence of MAO-A- but not MAO-B-selective inhibitors prevented the covalent incorporation of [3H]Ro 41-1049. The present results indicate that [3H]Ro 41-1049 is incorporated into a subunit of MAO-A, in the presence of NaBH3CN, and modifies a protein domain that is essential for the enzyme activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Pharmacol 1990 Mar
PMID:Characterization of the binding of [3H]Ro 41-1049 to the active site of human monoamine oxidase-A. 231 88

1. The effect of repeated isolation stress on MAO inhibitory activity (tribulin) in rat tissues as well as on plasma catecholamine levels was investigated. 2. Animals were subjected to a daily period of isolation (9 min) and sacrificed on days 1, 2, 4, and 5. 3. In brain and cerebellum the levels of both inhibitory activities were found to be significantly higher in animals sacrificed on days 1-2 than in either controls or animals sacrificed on days 4-5. 4. In heart and kidney the highest levels of both activities were found in animals sacrificed on days 4-5. 5. Plasma levels of dopamine on day 4 were significantly higher than those in controls or in any of the experimental groups. Plasma levels of epinephrine showed step-by-step increments from day 1 up to day 5, reaching statistical significance only on day 5. Plasma levels of norepinephrine were significantly increased on days 2, 4, and 5. 6. Under the experimental conditions of this study, we have shown a rapid and short-lasting increment of tribulin in the central nervous system. Its disappearance on days 4-5 could be related to adaptation to the novel situation. Changes in the peripheral tissues appeared later, and a similar adaptation was absent during the period of observation. 7. Tribulin would be related to the stressful situation not only as an anxiety-promoting agent but also in contributing to the maintenance of high levels of circulating catecholamines.
Cell Mol Neurobiol 1989 Mar
PMID:Repeated (isolation) stress increases tribulin-like activity in the rat. 271 79

1. We performed an enzymatic characterization of two different fractionation procedures of ventricles from rat hearts. The enzymatic assays covered succinic dehydrogenase as a marker for inner mitochondrial membranes, monoamine oxidase as a marker for outer mitochondrial membranes, NADPH-cytochrome c reductase and RNA as endoplasmatic reticular markers, acid phosphatase as a lysosomal marker, and lactic dehydrogenase as a marker for the "soluble" compartment; DNA was estimated for nuclear contamination. 2. The plasma membrane markers 5'-nucleotidase, Ca2+-ATPase, Mg2+-ATPase, Na+-K+-ATPase, and adenylate cyclase were determined. 3. The roughly prepared membrane fractions showed increased yields of the membrane markers; the number of beta receptors, determined with (-)-[3H] dihydroalprenolol and DL-propranolol, amounted to 68 +/- 6 fmol/mg protein (KD = 3390 +/- 450 pmol, Hill coefficient = 1.5). 4. The membrane fraction prepared with a linear sucrose gradient showed an increased inner mitochondrial membrane marker; presumably the outer mitochondrial membrane was stripped off. The beta-receptor number was 39 +/- 3 fmol/mg protein (KD = 6250 +/- 300 pmol; Hill coefficient = 1.2).
Cell Mol Neurobiol 1988 Jun
PMID:Beta-adrenergic receptors and enzymes in rat myocardial membranes: implications of fractionation procedures and beta-adrenoceptor antagonists. 284 52

Changes in the activity of three mitochondrial enzymes in rat liver after in vitro ischemia have been determined by enzyme histochemical methods. The changes were correlated with the appearance in the electron microscope of flocculent densities in the mitochondria indicative of irreversible cell injury. The flocculent densities were observed in rat liver after about 2 h of ischemia in vitro at 37 degrees C. At the same time the activity of glutamate dehydrogenase, localized in the mitochondrial matrix, started to decrease. However, the activities of succinate dehydrogenase localized in the inner membrane of mitochondria, as well as monoamine oxidase of the mitochondrial outer membrane did not change at that stage. It is concluded from the results of this study and those of others that flocculent densities are formed by denaturation of proteins of the mitochondrial matrix in which glutamate dehydrogenase takes part. It should be considered more as a sign than as the cause of cell death.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:A histochemical study of changes in mitochondrial enzyme activities of rat liver after ischemia in vitro. 287 57

Oxygen radical production by polymorphonuclear leucocytes stimulated the oxidation of adrenalin through the adrenochrome pathway. This was detected either spectrophotometrically at 480 nm or separated by hplc and detected radiochemically. The oxidation was detectable within 5 min and continued for at least 4 h. Over the adrenalin concentration range 0.3 microM to 10 mM more than 80% of the oxidation that occurred was through the adrenochrome pathway, the remainder being through the amine oxidase, catechol methyl transferase pathway. Medium isolated after stimulation of the polymorphonuclear leucocytes was also able to oxidise adrenalin to adrenochrome. The results provide a cellular mechanism for the formation of adrenochrome and the other metabolites on this pathway of adrenalin metabolism, in inflammatory conditions where polymorphonuclear leucocyte infiltration occurs.
J Mol Cell Cardiol 1985 Apr
PMID:The adrenochrome pathway: the major route for adrenalin catabolism by polymorphonuclear leucocytes. 299 37

Our previous work has shown that low concentrations of 4-fluoro-3-nitrophenyl azide (FNPA) (0.01-1 microM) photodependently inhibited only the type B monoamine oxidase in rat brain [Biochem. Pharmacol. 34:781-785 (1985)]. Evidence is presented in this paper indicating that higher concentrations of FNPA (15 microM) photodependently inhibit type A monoamine oxidase (MAO-A) from human placenta. FNPA acted as a competitive inhibitor for human placental MAO-A in the dark (Ki = 10 microM) when [14C]serotonin was used as the substrate. The inhibition of MAO-A activity by FNPA was concentration dependent and also irradiation time dependent. The specificity of the photodependent incorporation of FNPA to MAO-A was shown by the protective effect of serotonin during the irradiation. The kinetic analysis showed that the Vmax was decreased whereas the Km was not changed after FNPA was photolyzed with MAO-A. Furthermore, there was no recovery of MAO-A activity upon washing of the photolyzed FNPA-enzyme mixture. These results suggest that FNPA may be covalently bound to the substrate-binding site. Thus, under the present experimental conditions, FNPA is a suitable photoaffinity labeling probe for human placental MAO-A. This is the first photoaffinity label for MAO-A, which may be useful for characterizing the substrate-binding site of this enzyme.
Mol Pharmacol 1988 Feb
PMID:Photoaffinity labeling of human placental monoamine oxidase-A by 4-fluoro-3-nitrophenyl azide. 334 83

Brief incubation of isolated rat hepatocytes in the presence of the oleate-bovine serum albumin complex resulted in a release to the cytosol of a portion of hexokinase (EC 2.7.1.1) normally bound to intracellular membranes. This was correlated with an increase of the negative surface potential of the outer mitochondrial membrane, as measured in situ by determining changes of Km of monoamine oxidase (EC 1.4.3.4). It is suggested that non-esterified fatty acids produce a partial release of bound hexokinase in the liver cell by changing the surface charge of intracellular membranes.
Mol Cell Biochem 1988 Jan
PMID:Effect of oleate on the apparent Km of monoamine oxidase and the amount of membrane-bound hexokinase in isolated rat hepatocytes: further evidence for the controlling role of the surface charge in hexokinase binding. 337 76

1. The 4-fluoro analogue of the monoamine oxidase-inhibiting antidepressant tranylcypromine was compared to the parent drug with regard to the following: inhibition of monoamine oxidases A and B in vitro and ex vivo; levels of both drugs in brain, liver, and blood after injection of equimolar doses; and effects on brain levels of the amines 2-phenylethylamine, tryptamine, norepinephrine, dopamine, and 5-hydroxytryptamine. 2. 4-Fluorotranylcypromine was found to be 10 times more potent than tranylcypromine at inhibiting monoamine oxidases A and B in vitro in rat brain homogenates. 3. After administration (0.1 mmol/kg, ip), 4-fluorotranylcypromine attained higher brain and liver levels and provided greater availability than did tranylcypromine after the injection of an equimolar amount. 4. At the dose employed, the ex vivo monoamine oxidases A and B inhibitory profiles in brain and liver over a 24-hr period following tranylcypromine and 4-fluorotranylcypromine treatment were not different from each other. 5. Although the drugs had similar effects on inhibition of brain MAO ex vivo, they differed from one another at several time intervals in the increases in concentrations of 2-phenylethylamine, tryptamine, norepinephrine, dopamine, and 5-hydroxytryptamine produced in brain. 6. In conclusion, fluorination of tranylcypromine in the 4 position of the phenyl ring produced a drug which was more potent than the parent drug at inhibiting MAO in vitro and attained higher levels in brain than did tranylcypromine itself after intraperitoneal injection of equimolar amounts of the drugs. 4-Fluorotranylcypromine increased the concentrations of trace amines, catecholamines, and 5-hydroxytryptamine in brain at most time intervals following intraperitoneal injection, and at some time intervals there were differences from tranylcypromine with regard to the amine concentrations produced.
Cell Mol Neurobiol 1987 Sep
PMID:Neurochemical and neuropharmacological properties of 4-fluorotranylcypromine. 344 Feb 83

Liver microsomes from uninduced mice and rats catalyze NADPH- and oxygen-dependent N-oxygenation of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). The N-oxide is the principal product and accounts for 95-96% of the total MPTP metabolized by microsomes. Demethylation of MPTP is detectable but the rate of nor-MPTP formation was never more than 4-6% of the rate of N-oxygenation. Studies on the biochemical mechanisms for N-oxygenation of MPTP suggest that this reaction is catalyzed exclusively by the flavin-containing monooxygenase. This conclusion is based on the effects of selective cytochrome P-450 inhibitors, positive effectors, and alternate substrates for the flavin-containing monooxygenase as well as on studies with the purified hog liver enzyme. MPTP is an excellent substrate for this monooxygenase with a Km of 30-33 microM. Limited studies with human liver whole homogenates suggest that N-oxygenation is also a major route for the metabolism of MPTP in man and the rate of N-oxide formation is approximately equal to the rate of mitochondrial monoamine oxidase-dependent MPDP+ (1-methyl-4-phenyl-2,3-dihydropyridinium species) production.
Mol Pharmacol 1986 Feb
PMID:Contribution of N-oxygenation to the metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by various liver preparations. 348 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>