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

-Ã(cid:141)Ã(cid:141)-D-ABSTRACT Enzymatic hydrolysis of acylamide of W-acyl-1 -/S-D-arabi-nofuranosylcytosine 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 A/"-palmitoyl-1-/?-D-arabi-nofuranosylcytosine by microsomal enzyme were identified stoichiometrically as 1-/8-D-arabinofuranosylcytosine and pal mitic acid. The microsomal enzyme showed an optimum pH at 9.0 in Tris-HCI buffer. Michaelis constant for W-palmitoyl-1-/8-D-arabinofuranosylcytosine was 2.5 x 10~5 M. The enzyme did not require divalent cations for the reaction. Mn2+ and Co2+ at 1 rriM strongly inhibited the reaction. The relative rates of hydrolysis of A/4-palmitoyl-, A/4-stearoyl-, W-lauroyl-, W4-bu-tyryl-, and A/4-behenoyl-1-/3-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-/8-D-arabino-furanosylcytosine from A/4-acyl derivatives of 1-/6-D-arabinofur-anosylcytosine. radioactivity Beckman system with automatic compensation.

[1]  T. Tsuruo,et al.  Membrane Affinity and Metabolism of A/4-Palmitoyl-1-/?-D-Arabinofuranosylcytosine into Cultured KB Cells1 , 2006 .

[2]  T. Tsuruo,et al.  Comparison of cytotoxic effect and cellular uptake of 1-beta-D-arabinofuranosylcytosine and its N4-acyl derivatives, using cultured KB cells. , 1979, Cancer research.

[3]  R. Wohlhueter,et al.  Transport and metabolism of deoxycytidine and 1-beta-D-arabinofuranosylcytosine into cultured Novikoff rat hepatoma cells, relationship to phosphorylation, and regulation of triphosphate synthesis. , 1978, Cancer research.

[4]  T. Ishida,et al.  N4-Behenoyl-1-β-d-arabinofuranosylcytosine as a Potential New Antitumor Agent , 1977 .

[5]  R. Borch.  Separation of long chain fatty acids as phenacyl esters by high pressure liquid chromatography. , 1975, Analytical chemistry.

[6]  D. Gish,et al.  ara-Cytidine acylates. Use of drug design predictors in structure-activity relationship correlation. , 1975, Journal of medicinal chemistry.

[7]  T. Chou,et al.  Metabolism and selective effects of 1-beta-D-arabinofuranosylcytosine in L1210 and Host tissues in vivo. , 1975, Cancer research.

[8]  J. Matsumoto,et al.  Amidohydrolases for N-short and long chain fatty acyl-L-amino acids from Mycobacteria. , 1972, Journal of biochemistry.

[9]  D. Gish,et al.  Immunosuppressive, antiviral and antitumor activities of cytarabine derivatives. , 1972, Biochemical pharmacology.

[10]  A. Ito,et al.  PROTEOLYTIC MICRODISSECTION OF SMOOTH-SURFACED VESICLES OF LIVER MICROSOMES , 1969, The Journal of cell biology.

[11]  H. Skipper,et al.  Experimental evaluation of potential anticancer agents. XXI. Scheduling of arabinosylcytosine to take advantage of its S-phase specificity against leukemia cells. , 1967, Cancer chemotherapy reports.

[12]  A. Ito,et al.  Evidence for biochemically different types of vesicles in the hepatic microsomal fraction. , 1966, Journal of biochemistry.

[13]  A. Goldin,et al.  Chemotherapy of leukemia L1210 in mice with 1-beta-d-arabinofuranosylcytosine hydrochloride. I. Influence of treatment schedules. , 1966, Cancer research.

[14]  J. Matsumoto,et al.  ENZYME HYDROLYZING N-LONG CHAIN ACYL-L-ASPARTIC ACIDS FROM MYCOBACTERIUM SMEGMATIS. , 1964, Journal of biochemistry.

[15]  Y. Yamamura,et al.  Acylamino acid deacylase from kidney. , 1963, Journal of biochemistry.

[16]  S. Nagai.  Enzymatic hydrolysis of N-palmitoyl-amino acids by Mycobacterium avium. , 1961, Journal of biochemistry.

[17]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[18]  W. C. Schneider.  Phosphorus compounds in animal tissues; a comparison of methods for the estimation of nucleic acids. , 1946, The Journal of biological chemistry.