Molecular Pharmacology, Vol 2, 574-584, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Studies on Adenosine Deaminase

I. Purification and Properties of Ox Heart Adenosine Deaminase

¹ Smith Kline and French Institute, Department of Pharmacology, University of Sydney, Australia

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.

Note:
ACKNOWLEDGMENT We are indebted to Mr. Frank Michal of this Institute for permission to include some of his unpublished pharmacologic data.