Arabinosyl nucleosides—XXXIII. Metabolism of 9-β-d-arabinofuranosyladenine in yeast cells

Growth of Saccharomyces cerevisiae is not affected by 9-β- d -arabinofuranosyladenine (β-araA) up to concentrations of 100 μM. Analytical studies revealed that β-ara-A is taken up by the yeast but is not intracellularly phosphorylated to the corresponding nucleotides; 27 per cent of the intracellular β-ara-A is deaminated to 9-β- d -arabinofuranosylhypoxanthine. However, incubation of the cells with ara-AMP results in a strong inhibition of cell proliferation with an ED 50 concentration of 8.3 μM. The ara-AMP-caused inhibition of cell proliferation can be abolished by coincubation with deoxyadenosine. The latter observation together with results from incorporation studies indicates that ara-AMP affects cell growth via inhibition of DNA synthesis. In vitro experiments with partially purified adenosine kinase from yeast revealed that β-ara-A and eight further aranucleosides as well as three deaminase inhibitors (diazepin derivatives) are either not substrates or poor ones for this enzyme.