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Thymidine kinase isoenzymes in human acute monocytic leukemia

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Summary

Two thymidine kinase isoenzymes, TK 3 and TK 4, from mononuclear leucocytes from a patient with acute monocytic leukemia, were purified and characterized in regard to the molecular weights and kinetic properties.

The molecular weights of TK 3 and TK 4 were 60 000 and 45 000, respectively. In the presence of 2 mM ATP, the molecular weight of TK 3 increased to 200 000, whereas the molecular weight of TK 4 was unchanged.

Studies of the kinetic properties showed clear differences between TK 3 and TK 4. With thymidine as substrate, TK 3 showed biphasic kinetics with a Km of 22 µM, and TK 4 showed Michaelis-Menten kinetics with a Km of 0.33 µM With ATP as substrate, TK 3 showed Michaelis-Menten kinetics with a Km of 100 µM, and TK 4 showed biphasic kinetics with a Km of 3.5 µM. With dTTP as inhibitor, TK 3 showed cooperative inhibition kinetics, and TK 4 showed non-cooperative competitive inhibition kinetics. The dTTP concentration at 50% inhibition was 75 µM for TK 3 but 380 µM for TK 4.

Comparison of the molecular weights and the kinetic properties of TK 3 and TK 4 with the corresponding data previously obtained for TK 1 and TK 2 from normal human lymphocytes indicate the existence of four thymidine kinase isoenzymes in human leucocytes.

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Munch-Petersen, B., Tyrsted, G. Thymidine kinase isoenzymes in human acute monocytic leukemia. Mol Cell Biochem 66, 185–191 (1985). https://doi.org/10.1007/BF00220786

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