Studies of catalysis by acetylcholinesterase. Synergistic effects of inhibitors during the hydrolysis of acetic acid esters

Terrone L. Rosenberry, Sidney A. Bernhard

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The inhibition patterns of several inhibitors of acetylcholinesterase were studied during the steady-state hydrolysis of three acetic acid esters. The competitive and uncompetitive inhibition constants were tabulated. Data on competitive inhibition are consistent with the assumption that all three acetic acid ester substrates and a dimethylcarbamic acid ester substrate are hydrolyzed at the same enzyme active site. Certain pairs of compounds appeared to bind simultaneously to the enzyme in a ternary complex, and such pairs acting in concert inhibited acetylcholine hydrolysis to an extent many times greater than that observed for either compound alone. A formal model of enzyme catalysis is proposed to account for these synergistic effects, and detailed examination of the inhibition data test the predictions of specific molecular interactions within the model. Compounds which act synergistically show evidence of simultaneously interacting with two regions of the active site; these regions are proposed to become separated as a result of a conformational change of the enzyme. A potential role for this conformational change in the cholinergic receptor mechanism of excitable membranes is discussed.

Original languageEnglish (US)
Pages (from-to)4308-4321
Number of pages14
JournalBiochemistry
Volume11
Issue number23
StatePublished - 1972
Externally publishedYes

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Acetylcholinesterase
Catalysis
Hydrolysis
Acetates
Enzymes
Catalytic Domain
Molecular interactions
Cholinesterase Inhibitors
Cholinergic Receptors
Substrates
Acetylcholine
Esters
Membranes
Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Studies of catalysis by acetylcholinesterase. Synergistic effects of inhibitors during the hydrolysis of acetic acid esters. / Rosenberry, Terrone L.; Bernhard, Sidney A.

In: Biochemistry, Vol. 11, No. 23, 1972, p. 4308-4321.

Research output: Contribution to journalArticle

Rosenberry, Terrone L. ; Bernhard, Sidney A. / Studies of catalysis by acetylcholinesterase. Synergistic effects of inhibitors during the hydrolysis of acetic acid esters. In: Biochemistry. 1972 ; Vol. 11, No. 23. pp. 4308-4321.
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