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Enzyme Catalyzation of the Deacylation of N⁴-Acyl Derivatives of 1-ß-D-Arabinofuranosylcytosine in the Mouse Liver Microsome¹

Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Toshima-ku, Tokyo 170, Japan

Enzymatic hydrolysis of acylamide of N⁴-acyl-1-ß-D-arabinofuranosylcytosine was studied. The highest enzyme activity among various homogenates from mouse tissues, as expressed by specific activity, was found in liver homogenate. More than 50% of the activity in the liver was found in the microsomal fraction. The hydrolysis products of N⁴-palmitoyl-1-ß-D-arabinofuranosylcytosine by microsomal enzyme were identified stoichiometrically as 1-ß-D-arabinofuranosylcytosine and palmitic acid. The microsomal enzyme showed an optimum pH at 9.0 in Tris-HCI buffer. Michaelis constant for N⁴-palmitoyl-1-ß-D-arabinofuranosylcytosine was 2.5 x 10^-5 M. The enzyme did not require divalent cations for the reaction. Mn²⁺ and Co²⁺ at 1 mM strongly inhibited the reaction. The relative rates of hydrolysis of N⁴-palmitoyl-, N⁴-stearoyl-, N⁴-lauroyl-, N⁴-butyryl-, and N⁴-behenoyl-1-ß-D-arabinofuranosylcytosine were 100, 47.6, 31.3, 15.9, and 9.1, respectively. The enzyme might play an important role in the formation of 1-ß-D-arabinofuranosylcytosine from N⁴-acyl derivatives of 1-ß-D-arabinofuranosylcytosine.

¹ This work was supported by Grant-in-Aids for Cancer Research from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare, Japan.

² To whom requests for reprints should be addressed.

³ Research Fellow from Asahi Chemical Industry, Ltd., Nobeoka, Japan.

Received 9/ 8/81. Accepted 3/12/82.

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