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)

The phospholipid requirement of membrane-bound enzymes may depend on several reasons. In our laboratory we have investigated lipids (1) as a bidimensional medium required for the movement of Coenzyme Q, a lipid-soluble cofactor of the mitochondrial respiratory chain, and (2) as a hydrophobic environment necessary to impose the proper conformation to membrane-bound enzymic proteins. We have found that Coenzyme Q, once reduced by NADH dehydrogenase, must cross the inner mitochondrial membrane; only quinones having long isoprenoid side chains can easily cross phospholipid bilayers, and this is the reason why a short chain quinone such as CoQ-3 inhibits NADH oxidation. The incapability of short quinones to cross lipid bilayers is due to their disposition in the lipid bilayer, stacked within the phospholipids. The conformational role of lipids has been investigated indirectly observing the kinetics of membrane-bound enzymes, e.g. the mitochondrial ATPase, and directly by circular dichroism. Lipid removal or lipid perturbation with organic solvents induce a decrease of alpha-helical content in mitochondrial proteins, and give rise to a series of kinetic changes in ATPase, including uncompetitive inhibition, increased activation energy, and loss of cooperativity in oligomycin inhibition. The recognition of a conformational role of lipids has allowed us to postulate a working hypothesis for the mechanism of action of general anesthetics. Such drugs have been found by us, by means of spin labels and fluorescent probes, to disrupt lipid protein interactions in several membranes, including synaptic membranes. The loosening of such interactions is believed to induce conformational changes, which will alter ion transport systems necessary to the propagation of neural impulses. Conformational changes induced by anesthetics have been found by us both directly by circular dichroism and indirectly by enzyme kinetics. The conformational effect of anesthetics is not directly exerted on the proteins but is mediated through the lipids. In agreement with this hypothesis we have found that membrane-bound acetylcholinesterase is inhibited by anesthetics, whereas the solubilized enzyme is not inhibited. However, binding of the solubilized enzyme to phospholipids restores anesthetic inhibition.
Mol Cell Biochem 1978 Nov 30
PMID:Biophysical studies on agents affecting the state of membrane lipids: biochemical and pharmacological implications. 15 58

The effect of the cholinergic activator, phenyltrimethylammonium, on the ESR spectra of spin-labeled membrane bound acetylcholinesterase was studied; a reduction of maximal hyperfine splitting of the anisotropic ESR spectrum by 2 G was observed. The influence of phenyltrimethylammonium was prevented by the two cholinergic blocking agents d-tubocurarine and alpha-cobratoxine. The present results indicate that the conformation change of the esteratic site of membrane acetylcholinesterase is triggered by the binding of phenyltrimethylammonium to the cholinoreceptor site.
Mol Cell Biochem 1976 Dec 10
PMID:An ESR study of the postsynatpic membrane acetylcholinesterase of Torpedo marmorata electric organ. 18 29

Modification of the lipid phase structure of the erythrocyte membrane by phospholipases A2, C and D as well as the partial depletion of cholesterol was shown to be accompanied by the change of the acetylcholinesterase (AChE) UV-sensitivity. The ability of UV-light to change the catalytic properties (Km) of the membrane-bound AChE not observed for free AChE (constant value of Km) and known as the phenomenon of photochemical allotopy, is retained in the cholesterol depleted membranes and disappears after an enzymatic treatment of the membranes by phospholipases. The possible non-photochemical influence of the membrane lipid phase in response to UV-damage of membrane-bound AChE is discussed.
Mol Biol (Mosk)
PMID:[Effect of the state of the lipid phase of the membrane on the effectiveness of photochemical modification of erythrocyte acetylcholinesterase]. 66 22

The effects of lanthanum on the activity of purified preparations of acetylcholinesterase (AChE) from the electric organ of E. electricus and on the activity of AChE in intact electroplaques from the same species were studied. 0.1 mM LaCl3 produced an initial inhibition of purified AChE which was followed by a delayed activation of the enzyme. Upon pretreatment of purified enzyme with LaCl3, initial activity was markedly increased. LaCl3 exerted a marked, concentration-dependent inhibition of intact cell AChE. La3+ and Ca2+ appear to interact competitively. In the presence of both 10 mM CaCl2 and 0.1 mM LaCl3, the initial activitity of purified AChE was increased at lower ACh concentrations and inhibited at ACh concentrations greater than 3 X 10(-4) M. Inhibition of intact cell enzyme by 0.1 mM LaCl3 was relieved by increasing the CaCl2 concentration to 10 mM at ACh concentrations less than 2 X 10(-4) M. The data were analyzed assuming Michaelis-Menten kinetics and interpreted with reference to the differential binding of divalent and trivalent cations to regulatory anionic sites which are separate and distinct from the anionic site of the active center of the enzyme.
Mol Cell Biochem 1977 May 31
PMID:Interactions of lanthanum with purified and intact cell acetylcholinesterase of Electrophorus electricus. 88 82

The antimalarial drug chloroquine is found to inhibit Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase, Ca(2+)-ATPase, pNPPase and acetylcholinesterase activities in different organs of rat in vivo when injected for a certain periods of time. The inhibition seems to be due to the changes in the level of phospholipid, cholesterol and the fatty acid of the lipid and the alteration of the fluidity of the microsomal membranes. However, the enzyme activities return to the normal level in about 2-3 weeks after the discontinuation of the drug suggesting that the drug effect is reversible.
Mol Cell Biochem 1992 Dec 02
PMID:The in vivo inhibition of transport enzyme activities by chloroquine in different organs of rat is reversible. 133 12

1. The effects of retinoic acid, gamma-interferon, cytosine arabinoside, nerve growth factor, tumor necrosis factor, and 12-O-tetradecanoylphorbol 13-acetate on the human neuroblastoma cell line, LAN-5, were studied. Intracellular levels of acetylcholinesterase, neuron-specific enolase, catecholamines and related neurotransmitters, vasointestinal peptide, and substance P were evaluated after induction. 2. Cell morphology was strongly affected by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. The main effects of retinoic acid and gamma-interferon were the loosening of cell clusters and the extension of long neurites; cytosine arabinoside induced cell body swelling and marked neuritogenesis. Following 12-O-tetradecanoylphorbol 13-acetate treatment, the cells became small, round, and neuritic. Conversely, modifications induced by nerve growth factor and tumor necrosis factor were mild. Cell proliferation rate was reduced by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate, while nerve growth factor and tumor necrosis factor were devoid of effects. 3. Acetylcholinesterase activity was significantly stimulated by retinoic acid and by gamma-interferon. Neuron-specific enolase activity was unaffected by all treatments except 12-O-tetradecanoylphorbol 13-acetate, which enhanced it by 1.6-fold. 4. The cellular catecholamine and related metabolite content was lowered by retinoic acid and gamma-interferon, while cytosine arabinoside and, even more, 12-O-tetradecanoylphorbol 13-acetate showed a stimulatory activity on their intracellular accumulation. 5. Finally, the cell-associated vasointestinal peptide level was strikingly increased by gamma-interferon and, to a lesser extent, by retinoic acid, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. 6. It is concluded that the most relevant biochemical changes associated with LAN-5 cells differentiation involve the repertoire of neurotransmitters and neuropeptides. These events vary in quality and in quantity, likely due to the pattern complexity of gene expression triggered by each inducer in determining the diversity of neuronal phenotypes.
Cell Mol Neurobiol 1992 Jun
PMID:A combined evaluation of biochemical and morphological changes during human neuroblastoma cell differentiation. 135 48

The arrival of the nerve impulse to the nerve endings leads to a series of events involving the entry of sodium and the exit of potassium. Restoration of ionic equilibria of sodium and potassium through the membrane is carried out by the sodium/potassium pump, that is the enzyme Na+,K(+)-ATPase. This is a particle-bound enzyme that concentrates in the nerve ending or synaptosomal membranes. The activity of Na+,K(+)-ATPase is essential for the maintenance of numerous reactions, as demonstrated in the isolated synaptosomes. This lends interest to the knowledge of the possible regulatory mechanisms of Na+,K(+)-ATPase activity in the synaptic region. The aim of this review is to summarize the results obtained in the author's laboratory, that refer to the effect of neurotransmitters and endogenous substances on Na+,K(+)-ATPase activity. Mention is also made of results in the field obtained in other laboratories. Evidence showing that brain Na+,K(+)-ATPase activity may be modified by certain neurotransmitters and insulin have been presented. The type of change produced by noradrenaline, dopamine, and serotonin on synaptosomal membrane Na+,K(+)-ATPase was found to depend on the presence or absence of a soluble brain fraction. The soluble brain fraction itself was able to stimulate or inhibit the enzyme, an effect that was dependent in turn on the time elapsed between preparation and use of the fraction. The filtration of soluble brain fraction through Sephadex G-50 allowed the separation of two active subfractions: peaks I and II. Peak I increased Na+,K(+)- and Mg(2+)-ATPases, and peak II inhibited Na+,K(+)-ATPase. Other membrane enzymes such as acetylcholinesterase and 5'-nucleotidase were unchanged by peaks I or II. In normotensive anesthetized rats, water and sodium excretion were not modified by peak I but were increased by peak II, thus resembling ouabain effects. 3H-ouabain binding was unchanged by peak I but decreased by peak II in some areas of the CNS assayed by quantitative autoradiography and in synaptosomal membranes assayed by a filtration technique. The effects of peak I and II on Na+,K(+)-ATPase were reversed by catecholamines. The extent of Na+,K(+)-ATPase inhibition by peak II was dependent on K+ concentration, thus suggesting an interference with the K+ site of the enzyme. Peak II was able to induce the release of neurotransmitter stored in the synaptic vesicles in a way similar to ouabain. Taking into account that peak II inhibits only Na+,N(+)-ATPase, increases diuresis and natriuresis, blocks high affinity 3H-ouabain binding, and induces neurotransmitter release, it is suggested that it contains an ouabain-like substance.
Mol Neurobiol 1992
PMID:In search of synaptosomal Na+,K(+)-ATPase regulators. 136 48

In the present study the acute effect of intravenous aluminum chloride (1 mg/kg) on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities of rats was investigated. Aluminum was found to cross the blood-brain barrier (BBB) as indicated by the detection of aluminum in the cerebrospinal fluid (CSF) 30 min after femoral vein injection. Two hours following aluminum injection, ChAT activity in the basal forebrain and hippocampus was significantly reduced by 30% and 22%, respectively, whereas no change was observed in the caudate nuclei. On the other hand, AChE activity was significantly increased by 45% in the caudate nuclei, whereas little change was observed in other brain areas. This report demonstrates that rapid transport of Al across the BBB, and the acute nature of Al neurotoxicity in rats.
Mol Chem Neuropathol 1992 Aug
PMID:Aluminum-induced acute cholinergic neurotoxicity in rat. 138 51

The biochemical nature and relationship between the different isoforms of acetylcholinesterase (AChEs) secreted by adult Nippostrongylus brasiliensis was investigated, primarily via staining for enzyme activity and active-site labelling with [3H]-diisopropylfluorophosphate (DFP). Analysis by 1-dimensional SDS-PAGE under non-reducing conditions revealed the existence of 2 proteins of 74-kDa and 39-kDa, and each protein resolved as 2 species by isoelectric focusing. Both AChEs were co-purified via affinity chromatography on 9-[N beta-(epsilon-aminocaproyl)-beta-aminopropylamino]-acridine-coupled Sepharose 6B, and utilised to raise a polyclonal rabbit antiserum. Examination of the expression of secretory AChEs by adult worms during their residence in the gastrointestinal tract showed that the initial secretion of both forms on day 4 post-infection switched to predominant secretion of the 39-kDa protein by day 8. Immunoprecipitation of 35S-labelled products of in vitro translation via RNA from day 4 and day 8 worms predicted a single primary translation product of 59 kDa. These data suggested that the 'switching' event seen in vivo most likely corresponded to processing of the 74-kDa molecule. This interpretation was supported by limited digestion with V8 protease and chymotrypsin, which showed that the 74-kDa and the 39-kDa proteins possessed structural similarities.
Mol Biochem Parasitol 1992 Jul
PMID:Characterisation of the secretory acetylcholinesterases from adult Nippostrongylus brasiliensis. 150 47

This paper examines inhibition of acetylcholinesterase (AchE) and butyrylcholinesterase (BuchE) by tetrahydroaminoacridine (THA), an acridine analog under consideration for palliative treatment of Alzheimer's dementia. THA causes linear mixed inhibition of AchE hydrolysis of acetylthiocholine, a cationic substrate (KI = 3.8 x 10(-9) M), and linear competitive inhibition of AchE hydrolysis of 7-acetoxy-4-methylcoumarin, an uncharged substrate (KI = 6.8 x 10(-9) M), and N-methyl-7-dimethylcarbamoxyquinolinium, a cationic carbamate (KI = 1.5 x 10(-8) M). Propidium association with AchE in the presence of saturating concentrations of THA is characterized by a dissociation constant of 7.7 +/- 0.7 x 10(-6) M, a value within 2-fold of the dissociation constant in the absence of THA. Association of THA with AchE is, therefore, not mutually exclusive with association of propidium at the peripheral anionic site. Moreover, THA causes dissociation of decidium complexes with AchE at concentrations compatible with a dissociation constant of 7.0 +/- 0.4 x 10(-9) M. Similar relationships were observed for THA inhibition of BuchE hydrolysis of butyrylthiocholine (KI = 2.5 x 10(-8) M) and dissociation of decidium complexes with BuchE (KD = 1.9 +/- 0.1 x 10(-8) M). These kinetic and equilibrium data uniformly indicate that THA associates with AchE and BuchE with high affinity and that the subsequent inhibition comes about through ligand association at the active center rather than at a peripheral site. The noncompetitive component of inhibition reflects association of THA with the acyl-enzyme intermediate, with subsequent effects on the rate of deacylation.
Mol Pharmacol 1992 Feb
PMID:Interaction of tetrahydroaminoacridine with acetylcholinesterase and butyrylcholinesterase. 153 17


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