Effect of local pH changes caused by substrate hydrolysis on the activity of membrane-bound acetylcholinesterase.

Silman, H.I.; Karlin, Arthur

doi:10.1073/pnas.58.4.1664

Cited by 79 publications

(21 citation statements)

References 13 publications

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“…The behavior of the membrane-bound enzyme according to the pH could result from modifications of the micro-environment of the enzyme during microsomal preparation. Indeed the breaking up of the membrane architecture notably the electrostatic bonding with phospholipids of a membrane enzyme can cause a shift of pH optimum (Silman and Karlin, 1967;Coleman, 1973;Houslay and Tipton, 1973). Umbilical artery provided qualitative and quantitative information on tresperimus metabolism in man.…”

Section: In Vitro Metabolism Of Tresperimus By Human Vascular Ssaomentioning

confidence: 99%

In Vitro Metabolism of Tresperimus by Human Vascular Semicarbazide-Sensitive Amine Oxidase

Claud¹,

Artur²,

Laine³

2002

Drug Metab Dispos

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ABSTRACT:Tresperimus (Cellimis), a new immunosuppressive agent is mainly eliminated through an extensive nonhepatic metabolism, in which the oxidative deamination of the primary amine of the drug takes a preponderant part. We have previously demonstrated the ability of human plasma semicarbazide-sensitive amine oxidase (SSAO) to catalyze this reaction. Therefore, the suitability of human umbilical artery, a tissue combining a high SSAO activity with monoamine oxidase activity, to study tresperimus metabolism was tested, and the kinetic behavior of tissue-bound SSAO was compared with that of plasma soluble SSAO.

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Section: In Vitro Metabolism Of Tresperimus By Human Vascular Ssaomentioning

confidence: 99%

In Vitro Metabolism of Tresperimus by Human Vascular Semicarbazide-Sensitive Amine Oxidase

Claud¹,

Artur²,

Laine³

2002

Drug Metab Dispos

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“…Iso-osmolality was maintained by reciprocal changes in bicarbonate and chloride. The pH and C02 content of the medium in each box 2 Determination of the pK of nicotine. To determine the pK of nicotine a 100 mm nicotine hydrochloride and 150 mm sodium chloride solution was titrated at 370C with sodium hydroxide.…”

Section: Methodsmentioning

confidence: 99%

“…Change in hydrogen ion activity is a primitive and simple means by which organisms may alter metabolic reaction rates (1)(2)(3). This seems rather obvious when one considers that almost all enzymes exhibit pH optima and that most naturally occurring catabolic processes release protons (4,5).…”

Section: Introductionmentioning

confidence: 99%

The Simultaneous Determination of Muscle Cell pH Using a Weak Acid and Weak Base

Adler¹

1972

J. Clin. Invest.

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A B S T R A C T Should significant pH heterogeneity exist within cells then the simultaneous calculation of intracellular pH from the distribution of a weak acid will give a value closest to the highest pH in the system, whereas calculation from the distribution of a weak base will give a value closer to the lowest pH. These two values should then differ significantly. Intact rat diaphragms were exposed in vitro to varying bicarbonate concentrations (pure metabolic) and C02 tensions (pure respiratory), and steady-state cell pH was measured simultaneously either by distribution of the weak acid 5,5-dimethyloxazolidine-2,4-dione-"C (pH DMO) or by distribution of the weak base nicotine-'4C (pH nicotine). The latter compound was found suitable to measure cell pH since it was neither metabolized nor bound by rat diaphragms.At an external pH of 7.40, pH DMO was 7.17 while pH nicotine was 6.69-a pH difference of 0.48 pH units (P <0.001). In either respiratory or metabolic alkalosis both DMO and pH nicotine rose so that differences between them remained essentially constant. Metabolic acidosis induced a decrease in both values though they fell more slowly than did extracellular pH. In contradistinction, in respiratory acidosis, decreasing extracellular pH from 7.40 to 6.80 resulted in 0.35 pH unit drop in pH DMO while pH nicotine remained constant. In every experiment, under all external conditions, pH DMO exceeded pH nicotine.These results indicate that there is significant pH heterogeneity within diaphragm muscle, but the degree of heterogeneity may vary under different external conditions. The metabolic implications of these findings are discussed. In addition, the data show that true overPresented in part at the meeting of the American Federation for Clinical Research and published in abstract form: 1970. Clin. Res. 18: 493.

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“…The data of Pennington et al [12] indicate that AChE bound to an artificial matrix is more resistant to longer exposure at 60°C than the free enzyme. Silman and Karlin [ 10] have established that unlike soluble-AchE, membrane-AChE requires the presence of a low concentration of buffer (e.g., 2 mM phosphate) to exhibit a bell-shaped response to changes in pH. In light of these observations, the different kinetic behavior of the two states of the enzyme is most easily explained by assuming that solubilization induces a change in the tertiary structure of the active site of the enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…This can be explained by either of the following two hypotheses: 1) one portion of the molecules having AChE activity is an integral part of the membrane structure while the other is a peripheral component, or 2) all of the AChE molecules are part of a peripheral protein pool [9] but the ionic strength, pH and temperature conditions in our experiments are such that only half of the enzyme activity is solubilized. Silman and Karlin [ 10] have shown that pre-incubation of the membranes with 1 M NaC1 solubilizes over 90% of the AChE activity. Their data would tend to support the hypothesis of a single pool of peripheral AChE molecules.…”

Section: Discussionmentioning

confidence: 99%

Some differences between soluble and membrane‐bound acetylcholinesterase from Electrophorus electricus

Robaire

Kato

1973

FEBS Letters

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Effect of local pH changes caused by substrate hydrolysis on the activity of membrane-bound acetylcholinesterase.

Cited by 79 publications

References 13 publications

In Vitro Metabolism of Tresperimus by Human Vascular Semicarbazide-Sensitive Amine Oxidase

In Vitro Metabolism of Tresperimus by Human Vascular Semicarbazide-Sensitive Amine Oxidase

The Simultaneous Determination of Muscle Cell pH Using a Weak Acid and Weak Base

Some differences between soluble and membrane‐bound acetylcholinesterase from Electrophorus electricus

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