Detail of "892-48-8"

Reference

5'-Deoxy-5'-methylthioadenosine phosphorylase - III

5'-Deoxy-5'-methylthioadenosine phosphorylase - III. Role of the enzyme in the metabolism and action of 5'-halogenated adenosine analogs. Savarese, Todd M.; Chu, Shih Hsi; Chu, Ming Yu; Parks, Robert E., Jr. (Dep. Med., Roger Williams Gen. Hosp., Providence, RI 02912, USA). Biochem. Pharmacol., 34(3), 361-7 (English) 1985. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) 5'-Deoxy-5'-halogenated adenosines are alternative substrates for 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAPase) [61970-06-7], an enzyme responsible for the metab. of 5'-deoxy-5'-methylthioadenosine (MTA) [2457-80-9], a byproduct of polyamine biosynthesis. The relative reactivity of these nucleosides with MTAPase from HL-60 human promyelocytic leukemia cells is MTA > 5'-deoxy-5'-fluoroadenosine [731-98-6] > 5'-chloro-5'-deoxyadenosine [892-48-8] > 5'-bromo-5'-deoxyadenosine (5'-BrAdo) [4337-12-6] > 5'-deoxy-5'-iodoadenosine (5'-IAdo) [4099-81-4]. In MTAPase-contg. cells, the adenine released from the 5'-halogenated adenosine was incorporated into adenine nucleotide pools; cleavage by MTAPase appeared to be the rate-limiting step in this process. 5'-BrAdo and 5'-IAdo were growth inhibitors (EC50 values <10 mM) of MTAPase-contg. cell lines (HL-60 human promyelocytic leukemia and L5178Y murine lymphoblastic leukemia) but were much less active (EC50 values >65 mM) against MTAPase-deficient cell lines (CCRF-CEM human T cell leukemia and L1210 murine leukemia). The full cytotoxicity of these compds., therefore, appeared to be related to their phosphorolysis by MTAPase. Indirect evidence suggests that 5-halogenated ribose-1-phosphate derivs. of 5'-BrAdo or 5'-IAdo produced by the MTAPase reaction were the active metabolites of these 5'-halogenated adenosines.

Adenosine and 5'-chloro-5'-deoxyadenosine inhibit the phosphorylation of phosphatidylinositol and myosin light chain in calf aorta smooth muscle

Adenosine and 5'-chloro-5'-deoxyadenosine inhibit the phosphorylation of phosphatidylinositol and myosin light chain in calf aorta smooth muscle. Doctrow, Susan R.; Lowenstein, John M. (Grad. Dep. Biochem., Brandeis Univ., Waltham, MA 02254, USA). J. Biol. Chem., 260(6), 3469-76 (English) 1985. CODEN: JBCHA3. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 13 Smooth muscle from calf aorta is homogenized and centrifuged. The insol. material is subjected to sucrose d. gradient centrifugation. When the heaviest fraction so obtained is incubated with radioactive ATP, 2 components incorporate most of the acid-insol. radioactivity. One is a phosphoprotein with a mol. wt. of 21,000, identified as myosin light chain by its mol. wt., pI, and pptn. by antibody to calf aorta myosin. Its phosphorylation is strongly inhibited by EGTA, in agreement with published reports that myosin light chain kinase of smooth muscle is Ca2+ dependent. The other product is of low mol. wt., is extd. into acidic CHCl3-MeOH, and has been identified as phosphatidylinositol 4-phosphate. Adenosine [58-61-7] and 5'-chloro-5'-deoxyadenosine [892-48-8], which are vasodilators, inhibit the phosphorylation of both substrates. Phosphorylation of phosphatidylinositol is inhibited at lower concns. of the nucleosides than is the phosphorylation of myosin light chain. The inhibitory effects of the 2 nucleosides are not assocd. with changes in the concn. of cAMP. The precise function of phosphatidylinositol phosphorylation in smooth muscle is not known, but correlations between smooth muscle contraction and increased turnover of phosphatidylinositol and its mono- and diphosphates have been reported. Myosin light chain is phosphorylated under conditions which favor smooth muscle contraction. The inhibitory effects of adenosine described here are consistent with their physiol. action as vasodilators.