Inosine formation from adenosine

Slide 3 (Fig.l) shows that adenosine from the medium is rapidly converted to inosine,probably on the cell membrane, since no adenosine is detectable inside the cell. Inosine is rapidly converted to IMP in the normal cell,but in mutant cells it is converted to hypoxanthine. Effective AMP formation from adenosine in mutant cells is lower than in normal cells, indicating a shift towards hypoxanthine formation. 

In a similar way, enzymes from Azotobacter vinelandii catalyze the transfer of phosphate from adenosine 5-triphosphoric acid and inosine 5-tri-phosphoric acid to the 2-deoxypentonucleoside monophosphates, with the formation of the pyrophosphates and triphosphates. ... 

Scheme 12.97. Formation of adenosine phosphate from inosine. EC numbers and some graphic materials provided in this scheme have been taken from appropriate links in a URL starting with http //www.chem.qmul.ac.uk/iubmb/enzyme/.

A consideration of Bic possible pathways to account for nucleoside utilization indicated that the results could not be explained deciavely by the formation of hypoxantbine or adenine from the nucleosides. Hypoxanthinc was not a precursor of nucleic acids in the rat (200). Furthermore, free adenine (which might have been formed conceivably from inosine by successive amination and hydrolysis of the hypoxantbine riboside) was not formed from inosine. This was shown by the following experiment a large dose of unlabeled adenine with either labeled inosine or labeled adenosine was administered to rats (211) and 2,8-dioxyadenine, hich was deposited in the kidneys as a result of the administration of a large dose of adenine, was isolated (201, 214), analyzed for isotope content, and found to have trapped only a slight amount of radioactivity from either nucleoside (211). 

The reaction catalyzed by polynucleotide phosphorylase is the reversible formation of polymer from nucleoside 5 -pyrophosphates. Mg++ is required. The diphosphates of adenosine, inosine, guanosine, uridine, and cytidine all react, but the reaction with GDP is poor compared with the other nucleotides. The polymer contains 3 -5 linkages, and when... 

A reaction similar in type to that described above has been demonstrated in liver extracts by Wajzer and Baron for inosine-3 -phosphate synthesis from hypoxanthine and ribose-3-phosphate. The formation of the mononucleotide, adenylic acid, by the phosphorylation of adenosine by adenosinetriphosphate has also been described. The significance and integration of these different reactions remains a major problem for future effort. 

Write the mechanism of the formation of adenylosuccinate from inosine monophosphate, the second step in adenosine biosynthesis (Figure 24.12). 

ADP was also found to be a phosphate donor in the flavokinase reaction above, but the maximal velocity of formation of riboflavin 5 -phosphate was only about one-half that obtained with ATP. The Ks for ATP and ADP are, respectively, 1.7 X 10 M and 1.6 X 10 M (124). Englard (123) observed that purified flavokinase from brewer s yeast still contained myokinase, and attributed the activity of ADP to this contamination. He reported that in the presence of Zn++, when the myokinase contaminant is virtually inactive, flavokinase activity proceeded with ATP but not with ADP. However, there still appears to be some doubt whether ADP can be completely excluded as a phosphate donor in the flavokinase reaction on these grounds (124). Inosine triphosphate is inactive and adenoitine 6 -phosphate has been reported to be a competitive inhibitor of the reaction (121, 122). Ei ard (123) believes that the inhibition by adenosine 5 -phosphate is probably due to the competition of myokinase reaction with flavokinase for the available ATP when both reactions are activated by Mg++ adenosine 5 -phosphate did not inhibit flavokinase in the presence of Zn++ when myokinase was inactive. 

The kinetics of water replacement by nucleosides such as inosine or 1-methylinosine have been recorded for cw-[Pt(OH2)2(NH3)2], [Pt(OH2)(dien)], and related complexes (dien is 1,4,7-triazaheptane). The reactions of [Pt(OH2)(i ,R-dach)] with r(GpA) [R,R-dach = 1R,2R-cyclohexanediamine r(GpA)= guanyl(3 -5 )adenosine] under pseudo-first-order conditions revealed formation of a 1 1 aqua intermediate which decayed into a variety of chelate products, in some cases reversibly. The displacement of guanosine from cw-[Pt(Gua)(NH3)2] by CN was followed by... 

---