IV NUCLEOTIDE SYNTHESIS 9I 



E. Nucleotide Synthesis 



I. Occurrence of tiucleotic/es in tissues 



Inosinic acid and the mono-, di-, and triphosphates of adenosine, guanosine cyti- 

 dine, and vundine have been demonstrated in the cytoplasm of yeast, various animal 

 tissues and tumors of mice and rats (Smith and Mills, 1954, 1954a; Schmitz, 

 1954a, b; Schmitz et al., 1954a, b, 1955a, b; Bergkvist and Deutsch, 1954a, b) 

 and probably occur in all tissues. Nucleotide compounds such as uridine 

 diphosphate glucose, (UDP-glucose), UDP-acetylglucosamine, UDP-glucuronic 

 acid, UDP-acetylgalactosamine, UDP-galactose, UDP-xylose, and UDP-arabinose 

 have also been reported (Ginsberg et al., 1956). The concentrations of these sub- 

 stances vary from one tissue to another. The concentration of uridine diphos- 

 phoglucuronic acid is very low in sarcoma 37, while the oviduct of the hen 

 contains relatively high concentrations of a number of uridine compounds, in- 

 cluding UDP-acetylglucosamine phosphate and UDP-acetyl-galactosamine sulfate, 

 compounds not hitherto demonstrated in other tissues (Strominger, 1955). 

 Guanosine diphosphomannose occurs in yeast and in oviduct tissue. On the other 

 hand, the concentration of ATP is rather low in hen oviduct tissue. Cytidine diphos- 

 phoribitol and cytidine diphosphoglycerol have been found in Lactobacilli (Bad- 

 diley et al., 1956) while CDP-choline and CDP-ethanolamine occur in liver and 

 yeast (Kennedy and Weiss, 1956). Liver extracts contain adenosine diphospho- 

 ribose, adenosine diphosphoglutamic, and adenosine diphosphoaspartic acids 

 (Hansen and Hageman, 1956). 



Of the deoxyriboside nucleotides, only the th)'midylic and the deoxycytidylic 

 acid series of compounds have so far been reported. The mono-, di-, and triphos- 

 phates of these compounds occur in thymus tissue and thymidylate has also been 

 reported in E. coli (Potter and Schlesinger, 1955). Low concentrations of deoxy- 

 uridine, deoxycytidine, and thymidine have been found in many animxal tissues 

 (Schneider, 1955; Schneider and Brownell, 1956). The concentration of deoxyribo- 

 nucleosides is somewhat higher in lymphatic tissues and tumors than in most 

 normal animal tissues (Schneider, 1955; Lansford and Shive, 1955). The total 

 amount of deoxyribosidic compounds is about 10 y/g of liver or Novikoff tumor 

 but is increased by over 50% in the liver of a partially hepatectomized rat before 

 actual regeneration occurs (24 hours post operatively). In normal lever, 90% of 

 the deoxyribosidic compounds can be accounted for as deoxycytidine whereas in 

 the hepatoma, 50% of the deoxyribosidic compounds are attributable to de- 

 oxycytidine, deoxyuridine, and thymidine in the approximate ratio of (5:1:1) 

 while the rest are presumably due to nucleotides. About 25-30% of the deoxyri- 

 bosidic compounds of the liver 24 h. after partial hepatectomy are also found to 

 have nucleotide like properties (Schneider and Brownell, 1956). 



2. "De novo" purine synthesis 



The precursors of tissue purines have been elucidated as a result of studies on the 

 incorporation of labelled metabolites into the uric acid of the pigeon and rat, and 

 the nucleic acid purines of various animal tissues and inicroorganisms (Buchanan, 



Lileralure p. 124 



