INTERACTION OF 9-BETA-D-ARABINOFURANOSYLADENINE, 9-BETA-D-ARABINOFURANOSYLADENINE 5'-MONOPHOSPHATE, AND 9-BETA-D-ARABINOFURANOSYLADENINE 5'-TRIPHOSPHATE WITH S-ADENOSYLHOMOCYSTEINASE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (2) , 673-678
Abstract
9-.beta.-D-Arabinofuranosyladenine (ara-A) [an antineoplastic drug and its metabolites], 9-.beta.-D-arabinofuranosyl-AMP and 9-.beta.-D-arabinofuranosyl-ATP competitively inhibit the synthesis and hydrolysis of S-adenosylhomocysteine catalyzed by S-adenosylhomocysteinase [S-adenosylhomocysteine hydrolase (EC 3.3.1.1)] from mouse liver; the inhibitor constants were 5.0 .times. 10-6, 1.1 .times. 10-4) and 1.0 .times. 10-3 M, respectively. A time-dependent inactivation of the enzyme was observed when the enzyme was preincubation with ara-A, 9-.beta.-D-arabinofuranosyl-AMP or 9-.beta.-D-arabinofuranosyl-ATP. Ara-A was the most potent inactivator. The inactivation with ara-A was less pronounced in the presence of adenosine, S-adenosylhomocysteine, adenine, AMP or ADP, showed 1st-order kinetics, saturability and irreversibility. The rate of inactivation was half-maximal at 5 .times. 10-6 M ara-A; the rate constant of inactivation was 0.43 min-1 at saturating concentrations of ara-A. Ara-A was tightly but not covalently bound to the enzyme. Ara-A bound to the enzyme was not available for deamination to 9-.beta.-D-arabinofuranosylhypoxanthine catalyzed by the enzyme adenosine deaminase.