Interaction of 9-beta-D-arabinofuranosyladenine, 9-beta-D-arabinofuranosyladenine 5'-monophosphate, and 9-beta-D-arabinofuranosyladenine 5'-triphosphate with S-adenosylhomocysteinase.
9-beta-D-Arabinofuranosyladenine (ara-A), 9-beta-D-arabinofuranosyladenine 5'-monophosphate, and 9-beta-D-arabinofuranosyladenine 5'-triphosphate competitively inhibit both the synthesis and hydrolysis of S-adenosylhomocysteine catalyzed by S-adenosylhomocysteinase [S-adenosylhomocysteine hydrolase (EC 3.3.1.1)] from mouse liver, and the inhibitor constants were 5.0 X 10(-6), 1.1 X 10(-4), and 1.0 X 10(-3) M, respectively. A time-dependent inactivation of the enzyme was observed when the enzyme was preincubation with ara-A, 9-beta-D-arabinofuranosyladenine 5'-monophosphate, or 9-beta-D-arabinofuranosyladenine 5'-triphosphate. ara-A was the most potent inactivator. The inactivation with ara-A was less pronounced in the presence of adenosine, S-adenosylhomocysteine, adenine, adenosine 5'-monophosphate, or adenosine 5'-diphosphate, showed first-order kinetics, saturability, and irreversibility. The rate of inactivation was half-maximal at 5 X 10(-6) M ara-A, and 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.
D043383:Adenosylhomocysteinase; D000818:Animals; D001088:Arabinonucleotides / Q000494:pharmacology*; D001711:Biotransformation; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D008658:Inactivation, Metabolic; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D051379:Mice; D011485:Protein Binding; D014740:Vidarabine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D001084:Vidarabine Phosphate / Q000494:pharmacology*
D001088:Arabinonucleotides; D001084:Vidarabine Phosphate; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D014740:Vidarabine