Abstract
The antibiotic, 9-β-D-arabinofuranosyladenine (ara-A), among other adenosine analogs, irreversibly inactivates S-adenosylhaamocysteine (AdoHcy) hydrolase (EC 3.3.1.1.) (Chiang et al., 1981), the enzyme responsible for the metabolic degradation of the endogenous transmethylase inhibitor, AdoHcy. The inactivation of the enzyme in the presence of 2’-deoxyadenosine and ara-A obeys first-order kinetics, shows saturability ad is associated with irreversible reduction of enzyme-bound NAD+ (Hershfield, 1979; Helland & Ueland, 1981 a). ara-A and 2’-deoxyadenosine, as well as other adenosine analogs, have been shown to elevate the amount of AdoHcy in intact cells (Zimmerman et al., 1980). The present report summarizes recent observations in our laboratory on the inactivation of AdoHcy hydrolase and disposition of AdoHcy in cells exposed to ara-A.
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References
Chiang, P.K., Guranawski, A., and Segall, J.E. (1981). Irreversible inhibition of S-adenosylhomocysteine hydrolase by nucleoside analogs. Arch. Biochem. Biophys. 207, 175–184.
Helland, S. and Ueland, P.M. (1981 a). The relation between the functions of 9-β-D-arabinofuranosyladenine as inactivator and substrate of S-adenosylhomocysteine hydrolase. J. Pharm. Exp. Ther., in press.
Helland, S. and Ueland, P.M. (1981 b). Interaction of 9-β-D-arabinofuranosyladenine, 9-β-D-arabinofuranosyladenine 5’-monophosphate, and 9-β-D-arabinofuranosyladenine 5’-triphosphate with S-adenosylhomocysteinase. Cancer Res. 41, 673–678.
Hershfield, M.S. (1979). Apparent suicide inactivation of human lymphoblast S-adenosylhatocysteine hydrolase by 2’-deoxyadenosine and adenine arabinoside. A basis for direct toxic effects of analogs of adenosine. J. Biol. Chem. 254, 22–25.
Hershfield, M.S., and Kredich, N.M. (1980). Resistance of an adenosine kinase-deficient human lymphoblastoid cell line to effects of deoxyadenosine on growth, S-adenosylhomocysteine hydrolase inactivation, dATP accumulation. Proc. Natl. Acad. Sci. USA, 77, 4292–4296.
Palella, T.D., Andres, C.M., and Fox, I.H. (1980) Human placental adenosine kinase. Kinetic mechanism and inhibition. J. Biol. Chem. 255, 5264–5269.
Zimmerman, T.P., Wolber, G., Duncan, G.S., and Elion, G.B. (1980). Adenosine analogues as substrates and inhibitors of S-adenosylhomocysteine hydrolase in intact lymphoaytes. Biochemistry, 19, 2252–2259.
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Helland, S., Per Ueland, M. (1982). Inactivation of S-adenosylhomocysteine hydrolase by 9-β-D-arabinofuranosyladenine (ara-A) in intact cells. In: Biochemistry of S-Adenosylmethionine and Related Compounds. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-06343-7_91
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DOI: https://doi.org/10.1007/978-1-349-06343-7_91
Publisher Name: Palgrave Macmillan, London
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