Mammalian adenylosuccinate lyase. Participation in the conversion of 2'-dIMP and beta-D-arabinosyl-IMP to adenine nucleotides.
Adenylosuccinate synthetase (EC 6.3.4.4) from rabbit muscle efficiently catalyzes the formation of 2'-deoxyadenylosuccinate and beta-D-arabinosylade-nylosuccinate from 2'-dIMP and beta-D-arabinosylIMP (Spector, T. and Miller, RL. (1976) Biochim. Biophys. Acta 445, 509-517). These novel analogs of adenylosuccinate were synthesized with this enzyme and their kinetic constants were determined with adenylosuccinate lyase purified from Ehrlich ascites cells. 2'-Deoxyadenylosuccinate and beta-D-arabinosyladenylosuccinate were readily cleaved to 2'-dAMP and beta-D-arabinosylAMP, respectively. Their Km values were similar to that of adenylosuccinate (3-6 micronM) and their substrate efficiencies (V/Km) were 120 for 2-deoxyadenylosuccinate and 32 for beta-D-arabinosyl-adenylosuccinate, compared to a value of 100 for adenylosuccinate. The products of the reactions, 2'-dAMP and beta-D-arabinosylAMP, were competitive inhibitors with Ki values of 5 and 87 micronM, respectively. ATP and ADP were considerably weaker competitive inhibitors with Ki values of 200-300 micronM. IMP, GMP, xanthosine 5'-monophosphate, 6-thioIMP and 6-thioGMP had Ki values greater than 200 micronM.
D000818:Animals; D001089:Arabinose; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology*; D002855:Chromatography, Thin Layer; D003839:Deoxyadenosines; D003854:Deoxyribonucleotides; D007292:Inosine Nucleotides / Q000378:metabolism; D007700:Kinetics; D008025:Ligases / Q000378:metabolism*; D008297:Male; D051379:Mice; D013386:Succinates
D003839:Deoxyadenosines; D003854:Deoxyribonucleotides; D007292:Inosine Nucleotides; D013386:Succinates; D001089:Arabinose; D008025:Ligases