Abstract
Adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4.) has been purified 1060-fold from ox heart muscle. Adenosine, 2-deoxyadenosine, 2,6-diaminopurineriboside, 6-hydroxylaminopurineriboside and 6-chloropurine riboside are substrates of the enzyme, and adenosine and deoxyadenosine both exhibit substrate inhibition at concentrations of substrate about five times the Michaelis value. A number of 2-substituted adenosine analogs that have vasodilator properties have been shown to inhibit the enzyme competitively, and the cardiac glycoside ouabain has been found to be a competitive inhibitor. N6-methylation of adenosine and of several 2-substituted adenosines gave inhibitors with increased affinity for the enzyme active site; however, N6-dimethyl adenosine and adenosine-1-N-oxide inhibited noncompetitively. The relationship between the structure of the cardioactive adenosine analogs and their affinity for adenosine deaminase is considered.
ACKNOWLEDGMENT We are indebted to Mr. Frank Michal of this Institute for permission to include some of his unpublished pharmacologic data.
- Copyright ©, 1966, by Academic Press Inc.
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