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Research ArticleArticle

INHIBITION OF THE CHOLINESTERASE ACTIVITY OF HUMAN BLOOD PLASMA AND ERYTHROCYTE STROMATA BY ALKYLATED PHOSPHORUS COMPOUNDS

RALPH W. BRAUER
Journal of Pharmacology and Experimental Therapeutics February 1948, 92 (2) 162-172;
RALPH W. BRAUER
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Abstract

1. A series of akylated phosphorus compounds has been tested in vitro for their esterase inhibiting effects. The grouping P—O—R (R alkyl or aryl) is common to all active compounds. Other structural requirements are pointed out.

2. Plasma esterase inactivated by hexaethyl tetrapolyphosphate (HETP) or by tetraethyl pyrophosphate (TEPP) cannot be reactivated by the removal of the inhibitor in vitro, either by dialysis against active esterase for 24 hours, or by storage under conditions resulting in the destruction by hydrolysis of the inhibitor.

3. Interaction of HETP or TEPP with plasma esterase leads to the inactivation not only of the enzyme, but also of the inhibitor. Denatured esterase does not inactive the compounds. No simple molecular groupings were found capable of interacting with TEPP at a rate approaching that involved in its reaction with enzyme. Fibrinogen and crystalline albumin obtained from human blood plasma did not show any significant interaction with TEPP.

4. HETP containing P32 was prepared. It could be shown that upon interaction of this compound with plasma esterase no P32 could be found in the protein precipitated by ethanol, nor in the precipitate or in the supernatant of such preparations after dialysis. It was concluded that a stable combination between the esterase and a phosphorus containing moiety of HETP does not take place to a detectable degree.

5. On the basis of these data a working hypothesis has been proposed to describe the interaction of plasma esterase with inhibitors of the type here considered.

Footnotes

    • Received September 30, 1947.
  • 1948 by The American Society for Pharmacology and Experimental Therapeutics

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Journal of Pharmacology and Experimental Therapeutics
Vol. 92, Issue 2
1 Feb 1948
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Research ArticleArticle

INHIBITION OF THE CHOLINESTERASE ACTIVITY OF HUMAN BLOOD PLASMA AND ERYTHROCYTE STROMATA BY ALKYLATED PHOSPHORUS COMPOUNDS

RALPH W. BRAUER
Journal of Pharmacology and Experimental Therapeutics February 1, 1948, 92 (2) 162-172;

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Research ArticleArticle

INHIBITION OF THE CHOLINESTERASE ACTIVITY OF HUMAN BLOOD PLASMA AND ERYTHROCYTE STROMATA BY ALKYLATED PHOSPHORUS COMPOUNDS

RALPH W. BRAUER
Journal of Pharmacology and Experimental Therapeutics February 1, 1948, 92 (2) 162-172;
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