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- W1521751696 abstract "Abstract Deoxycytidine (dCyd) kinase, the enzyme that catalyzes 5′-monophosphorylation of 1-β-d-arabinofuranosylcytosine (ara-C) as well as dCyd, has been isolated and purified from a P815 mouse neoplasm sensitive to ara-C and from a P815/ara-C mouse neoplasm resistant to ara-C. The purified enzyme from drug-sensitive cells has a specific activity that is 40- to 90-fold higher than the specific activity of the kinase from P815/ara-C cells. The catalytic functions of the two kinases were compared in this study. Also noted were the differences in in vitro deoxyguanosine kinase activities in the lysates of the two cell types. The two dCyd kinase enzymes catalyze the phosphorylation of dCyd and ara-C only, have broad phosphate donor specificity, and are pH dependent. The K m 9s for dCyd as substrate were 10.6 and 8.2 µm for the two enzymes, and those for ara-C as acceptor were 30.2 and 21.0 µm. Nucleoside and nucleotide inhibition was similar for both enzymes except for the effects of deoxycytidine 5′-monophosphate and adenosine diphosphate. The enzymes have different turnover numbers (2.2 and 0.057 min -1 for the P815 and the P815/ara-C kinases, respectively), the temperature dependence of the catalysis of ara-C phosphorylation is dissimilar, and the specific activity of the P815 kinase with dCyd as substrate is greater than that with ara-C as substrate, but the reverse is true for the P815/ara-C dCyd kinase. The enzyme from ara-C-resistant cells is more sensitive to inhibition by p -chloromercuribenzoate, but both enzymes were inhibited by that reagent and other sulfhydryl reagents. The functional differences observed suggest that the two kinases are isoenzymes of one another. While we assume that genetic mutation produced the altered gene product, the exact nature of the mutation is not known." @default.
- W1521751696 created "2016-06-24" @default.
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- W1521751696 date "1978-04-01" @default.
- W1521751696 modified "2023-09-23" @default.
- W1521751696 title "Comparison of enzymatic activities of two deoxycytidine kinases purified from cells sensitive (P815) or resistant (P815/ara-C) to 1-beta-D-arabinofuranosylcytosine." @default.
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