Effect of Adenosine Analogues on Protein Carboxyimethyltransferase
[CANCER RESEARCH 47, 3656-3661, July 15, 1987] Effect of Adenosine Analogues on Protein Car boxy Imethyltransferase, S-Adenosylhomocysteine Hydrolase, and Ribonucleotide ReducÃase Activity in Murine Neuroblastoma Cells1 Robert F. O'Dea,2 Bernard L. Mirkin, Harry P. Hogenkamp, and Donna M. Barten Division of Clinical Pharmacology, Departments of Pediatrics, Pharmacology, and Biochemistry, University of Minnesota Health Sciences Center, Minneapolis, Minnesota 55455 ABSTRACT DZA, 2'-deoxyadenosine, and l-/3-D-arabinofuranosyladenine and the irreversible inhibitors AD, neplanocin A, and 3-deaza- The noncompetitive 5-adenosylhomocysteine (AdoHcy) hydrolase an neplanocin (3-7). AdoHcy hydrolase catalyzes the NAD+-de- tagonist adenosine dialdehyde (AD) has been shown to suppress the pendent oxidation of the 3'-hydroxyl group of AdoHcy (hydro- growth of cultured C-1300 murine neuroblastoma (MNB) cells. The lytic direction) or Ado (synthetic direction), resulting in the enzymatic sites at which AD and other nucleoside analogues exert their generation of 3'-keto-AdoHcy, 3'-ketoadenosine, and 3'-keto- cytotoxic effects have been postulated to include protein carboxyl- 4',5'-dehydroadenosine (2). Adenosine dialdehyde, generated methyltransferase (PCM), AdoHcy hydrolase, and ribonucleotide reduc Ãase. by periodate oxidation of adenosine, contains structural com AD (10~5 M) increased PCM activity 350% in suspensions prepared ponents (e.g., 3'-keto group) which are similar to the proposed from disrupted cells after 72 h of drug exposure; in contrast, 3-deaza- functional moieties of these enzyme-bound intermediates and adenosine ( IO-1 M) increased PCM activity 57%, whereas AdoHcy and has been reported to be a potent, irreversible inhibitor of sinefungin had no effect.
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