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141.
Conversion of 2,6-diamino-9-(2-hydroxyethoxymethyl)purine to acyclovir as catalyzed by adenosine deaminase 总被引:2,自引:0,他引:2
Adenosine deaminase (ADA) was partially purified from several sources using affinity chromatography. These enzymes have the capacity to catalyze the deamination of 2,6-diamino-9-(2-hydroxyethoxymethyl)purine (A134U) to form the antiviral agent acyclovir [9-(2-hydroxyethoxymethyl)guanine]. Their relative substrate efficiencies (Vmax/Km) with A134U (standardized to adenosine = 100) were: dog ADA, 0.092; human ADA, 0.015-0.029; rat ADA, 0.025; calf ADA, 0.016; and Escherichia coli ADA, 0.0003. In addition to having the lowest efficiency with A134U, the bacterial ADA was also distinguished by its lack of binding of the mammalian ADA inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine and by its weak binding to the 9-(p-aminobenzyl)adenine-agarose affinity column. Four minor metabolites of A134U and acyclovir have been reported to be produced in the rat. These compounds are oxidized on either the C-8 position of the ring or the terminal carbon of the side chain. Neither acyclovir nor any of these metabolites produced significant inhibition of calf intestine ADA. The oxidized metabolites containing an N-6 amino group were extremely slow substrates of this enzyme. 相似文献
142.
Previous results have indicated that 2'-deoxyadenosine (dAdo) and 2'-deoxytubercidin (dTub) are secreted by the mouse kidney. Secretion of dTub appeared to occur via the organic cation carrier [J. F. Kuttesch, Jr. et al., Biochem. Pharmac. 31, 3387 (1982)]. In the current study, the structural specificity of the secretory system for d Tub was probed by evaluating the renal clearance of several sugar-modified dTub analogs. The following sugar-modified derivatives also underwent apparent secretion: 3'-deoxy, arabinosyl, and xylosyl. These results suggest a lack of structural specificity of the secretory system for dTub. Tubercidin was apparently reabsorbed, analogous to the observation in mice that adenosine clearance is less than that of inulin. In related experiments, a transport maximum for dAdo could not be demonstrated due to the marked pharmacologic activity of dAdo. Cimetidine was found to selectively inhibit the organic cation secretory system since it blocked the renal secretion of tetraethylammonium but not that of p-amminohippurate in mice. Correspondingly, cimetidine prevented the renal secretion dTub; however, cimetidine did not inhibit the renal secretion of dAdo nor the renal reabsorption of Ado. These results suggest that renal secretion of dTub occurs via the organic cation carrier. The mechanisms for the renal secretion of dAdo and for the renal reabsorption of Ado may be unique and independent of the organic cation system. 相似文献
143.
2,4,6,2',4',6'-Hexa,- 2,5,2',5'-tetra- and 2,2'-dichloro-biphenyl (HCB, TCB and DCB) caused a type-I-binding spectrum with liver microsomes of phenobarbital treated rabbits. They had a high affinity to cytochrome P-450, which increased with decreasing chlorine content of the compounds. In parallel, the O-demethylation of p-nitroanisole was most effectively inhibited by DCB, to a smaller extent by TCB and HCB. Inhibition was competitive. While DCB was rapidly metabolized, metabolism of TCB was slow. No metabolites have been detected of HCB. Although HCB was not metabolized it stimulated the microsomal NADPH- and oxygen-consumption and also the reduction of cytochrome P-450. The stoichiometry of the NADPH- and O2-consumption of 2:1 in the presence of HCB is compatible with the notion that NADPH is oxidized to H2O, i.e. HCB may act as uncoupler of electron transport from monooxygenation. 相似文献
144.
Adenosine has a biphasic, [Mg2+]-dependent effect on the catalytic activity of dog heart adenylate cyclase. In the presence of 0.5 mM Mg2+, adenosine stimulated cyclic AMP formation, but when the cyclase was activated with 4 mM Mg2+ plus 0.5 mM Mn2+, adenosine inhibited catalytic activity in a dose-dependent fashion. Adenine, 3'-deoxyadenosine and selected purine-modified adenosine analogs stimulated the enzyme, whereas 2'-deoxyadenosine, 5'-deoxyadenosine and adenine-α-l-lyxofuranoside mimicked the inhibitory effect of adenosine on the Mg2+ plus Mn2+ stimulated enzyme. These results are consistent with the ‘two receptor’ model of Londos and Wolff [C. Londos and J. Wolff, Proc. natn. Acad. Sci. U.S.A.74, 5482 (1978)], but they raise the possibility of subtle organ and species differences in the chemical determinants of adenosine binding. Adenosine in both intracellular and extracellular compartments may modulate adenylate cyclase activity in the beating heart, in addition to its putative role in the regulation of coronary vascular resistance. 相似文献
145.
O.J.A. Gilmore Clare Reid Elizabeth T. Houang Elizabeth J. Shaw 《American journal of surgery》1978,135(2):156-159
In controlled experiments intraperitoneal povidone-iodine significantly reduced the mortality of mice (p < 0.01) and rats (p < 0.01) with induced peritonitis. Povidone-iodine irrigation of the rat colon before and after anastomosis did not interfere with healing or inhibit peritoneal adhesion formation. However, a newly formulated povidone-iodine solution containing increased PVP significantly reduced adhesion formation in a controlled study in rats. 相似文献
146.
Surface membrane localization of 3'- and 5'-nucleotidase activities in Leishmania donovani promastigotes 总被引:3,自引:0,他引:3
Distinct 3'- and 5'-nucleotidase activities were localized to the surface membrane of Leishmania donovani promastigotes using enzymatic reactions with live intact cells and fine structure enzyme-mediated cytochemical reactions with intact cells, cell homogenates, and isolated surface membranes. The results indicated that virtually all activity of both enzymes was restricted to the parasite surface membrane. Cytochemical localization results demonstrated that both activities were externally disposed on the intact organism, and were restricted to the external face of the isolated parasite surface membrane. The two activities were cytochemically differentiated by their substrate specificities and sensitivity to several inhibitors. On the basis of their cytochemical sensitivity to glutaraldehyde treatment, the two nucleotidase enzymes were distinguished from another external surface membrane enzyme, a nonspecific acid phosphatase. Results of the cytochemical assays further demonstrated the biochemical and structural asymmetry of the isolated parasite surface membrane with regard to the localization and distribution of the active sites of these two enzymes. 相似文献
147.
A retrospective study of knee function has been carried out in 85 patients who had fractures of the midshaft of the femur treated by three currently used methods. Patients who had undergone open medullary fixation, skeletal traction with early knee movements, and skeletal traction with an immobile knee have been compared. All the patients were reviewed personally, with a mean follow-up time of 5 years. We found that 30 per cent of all the patients had minor knee symptoms, and nearly half (45 per cent) had some ligamentous laxity. When bony union resulted, there was no difference in the effect on knee function between the three methods of treatment. Neither skeletal traction nor early knee movement had a harmful effect on the knee in the absence of any major ligamentous injury. 相似文献
148.
149.
James R Connor John H Melone Alan R Yuen Marian C Diamond 《Experimental neurology》1981,73(3):827-830
The present investigation was the first to measure the lengths of dendrictic segments from aged animals in different environments to determine if the rates of retraction that occur with age can be influenced by the external environment. Our results show that the sixth-order segments, which represent the segments most distal to the cell body, are 86% longer in animals which have spent their final 30 days in an enriched environment compared with their littermates from standard laboratory conditions. 相似文献
150.