Xanthines Adenosine

The effects of xanthine alkyl substitution on bronchocHlation have been summarized as foUows (60,61) alkylation is essential for adenosine... 

Figure 12 Gradient separation of bases, nucleosides and nucleoside mono- and polyphosphates. Column 0.6 x 45 cm. Aminex A-14 (20 3 p) in the chloride form. Eluent 0.1 M 2-methyl-2-amino-l-propanol delivered in a gradient from pH 9.9-100 mM NaCl to pH 10.0-400 mM NaCl. Flow rate 100 ml/hr. Temperature 55°C. Detection UV at 254 nm. Abbreviations (Cyt) cytosine, (Cyd) cytidine, (Ado) adenosine, (Urd) uridine, (Thyd) thymidine, (Ura) uracil, (CMP) cytidine monophosphate, (Gua) guanine, (Guo) guanosine, (Xan) xanthine, (Hyp) hypoxanthine, (Ino) inosine, (Ade) adenosine, (UMP) uridine monophosphate, (CDP) cytidine diphosphate, (AMP) adenosine monophosphate, (GMP) guanosine monophosphate, (IMP) inosine monophosphate, (CTP) cytidine triphosphate, (ADP) adenosine diphosphate, (UDP) uridine monophosphate, (GDP) guanosine diphosphate, (UTP) uridine triphosphate, (ATP) adenosine triphosphate, (GTP), guanosine triphosphate. (Reproduced with permission of Elsevier Science from Floridi, A., Palmerini, C. A., and Fini, C., /. Chromatogr., 138, 203, 1977.)...

HPLC coupled to MS was used for the determination of dimethyl xanthine metabolites in plasma.82 There have also been a number of methods published on the use of HPLC with a PDA detector. In 1996, Mei published a method for the determination of adenosine, inosine, hypoxanthine, xanthine, and uric acid in microdialysis samples using microbore column HPLC with a PDA detector.63 In this method, samples were directly injected onto the HPLC without the need for any additional sample treatment. 

Snyder, S. H., Adenosine as a mediator of the behavioral effects of xanthines, in Caffeine Perspective from Recent Research, Dews, P. B., Ed., Springer Verlag, Berlin, 1984, chap. 3. 

Smits, P., Schooten, J. and Thien, T., Cardiovascular effects of two xanthines and the relationship to adenosine antagonism. Clinical Pharmacological Therapy 45, 593-599, 1989. 

Phillis, J. W., O Regan, M. H. Walter, G. A. (1988). Effects of deoxycoformycin on adenosine, inosine, hypoxanthine, xanthine, and uric acid release from the hypoxemic rat cerebral cortex. J. Cereb. Blood Flow Metab. 8 (5), 733-41. 

The P-site of adenylyl cyclase inhibits cyclic AMP accumulation 308 There are four adenosine receptor subtypes 308 Xanthines block P2 but not P2 receptors 309... 

ATP diphosphohydrolase Diadenosine polyphosphatase 5 nucleotidase Nucleoside transporter Adenosine deaminase Adenosine kinase Xanthine oxidase Nucleoside phosphorylase... 

FIGURE 1 7-3 Adenosine metabolites. Adenosine is converted to inosine by adenosine deaminase. Removal of the ribose by nucleoside phos phorylase produces hypoxanthine, which is sequentially oxidized to xanthine and uric acid by xanthine oxidase. 

Species/Cultivar Adenosine Deaminase Xanthine Oxidase Uricase A1lantoinase Allantoicase ... 

J. Leppanen, J. Huuskonen, J. Savolainen, T. Nevalainen, H. Taipale, J. Vepsalainen, J. Gynther, T. Jarvinen, Synthesis of a Water-Soluble Prodrug of Entacapone , Bioorg. Med. Chem. Lett. 2000, 10, 1967-1969 R. Sauer, J. Maurinsh, U. Reith, F. Ftille, K. N. Klotz, C. E. Muller, Water-Soluble Phosphate Prodrugs of l-Propargyl-8-styryl-xanthine Derivatives, A2A-Selective Adenosine Receptor Antagonists , J. Med. Chem. 2000, 43, 440-448. 

For a wide variety of 6-aryl-3(2//)-pyridazinones (including those discussed in the chapter on cardiotonic agents and antithrombotics [1]), bronchodila-tor activity has been claimed in patents [104,114-116,129,423,424]. Thus, for instance, the bronchospasmolytic effects (guinea-pig tracheal-chain preparations) of compounds of type (99) have been found to exceed those of xanthines [425]. The therapeutic index of these compounds (which inhibit phosphodiesterase at lower concentrations than xanthines and do not interact with adenosine receptors) is larger than that of xanthines. 

Answer C. The child most likely has severe combined immunodeficiency caused by adenosine deaminase defidency. This enzyme deaminates adenosine (a nudeoside) to form inosine (another nucleoside). Hypoxanthine and xanthine are both purine bases, and the monophosphates are nucleotides. 

Azaguanine and thioguanine are catabolized by guanase, and both the purinethiones are degraded by xanthine oxidase. Methylation and demethylation is an important factor in the activity of the thiopurihes and certain adenine or adenosine analogues also. 

In the most important degradative pathway for adenosine monophosphate (AMP), it is the nucleotide that deaminated, and inosine monophosphate (IMP) arises. In the same way as in GMP, the purine base hypoxanthine is released from IMP. A single enzyme, xanthine oxidase [3], then both converts hypoxanthine into xanthine and xanthine into uric acid. An 0X0 group is introduced into the substrate in each of these reaction steps. The oxo group is derived from molecular oxygen another reaction product is hydrogen peroxide (H2O2), which is toxic and has to be removed by peroxidases. 

Despite the fact that the last mechanism may be basic for theophylline, a few xanthines, which in general lack the ability to bind with adenosine receptors, express the same, if not more broncholytic activity than theophylline. 

The purine ring-numbering scheme, 1, and structures of some simple purines, viz. adenine 2, guanine 3, caffeine 4, theophylline 5, adenosine 6, 2 -deoxyadenosine 7, guanosine 8, 2 -deoxyguanosine 9, xanthine 10, and hypoxanthine 11, are shown. 

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