388 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



building blocks for the extensive polynucleotide synthesis which is to occur. 

 Evidence as to the possible character of the intermediates actually involved 

 in the later steps of the biosynthetic processes is just beginning to be ac- 

 cumulated. 



a. The Constituents of the Acid-soluble Fractions 



The abundance of adenosine-5'-phosphates in the acid-soluble fractions 

 of tissues led initially to the tacit assumptions^ '^^^■'^^''^^■^''^ that tissue 

 AMP or its polyphosphates probably serve as the source of purines, at least 

 of adenine, for polynucleotide synthesis. The ATP of muscle did not receive 

 serious consideration as a polynucleotide precursor since the phosphate at- 

 tached to its ribose was one of the first biochemical moieties shown to be 

 but slowly renewedj^^S'^"^ and subsequently the same was demonstrated 

 for its nitrogen" •-'^^ and its adenine. ^-'^^ After the administration to rats 

 of adenosine-8-C'* a similarly low renewal of the muscle ATP was found.^^ 



However, after the administration of adenosine,^' the total acid-soluble adenine 

 from the muscle was 2.5 times as active as the ATP fraction (isolated as the Ba salts 

 according to LePage^^" and containing some ADP). Such a difference in activity was 

 not observed after the administration of inosine-S-C". The possibility of the presence 

 of a molecule such as the proposed diadenosine tetraphosphate^" '^'^ in which the two 

 adenine moieties were not renewed at equal rates was considered. The findings'' that 

 the 2'- and 3'-phosphates of adenosine are incorporated into muscle adenosine poly- 

 phosphates (separated chromatographically according to Cohn'^') several times as 

 extensively as is the 5'-isomer also fail to support a hypothesis that muscle ATP 

 arises simply by further phosphorj'lation of AMP. 



In contrast to the adenine derivatives in muscle, other soluble adenine 

 derivatives are rapidly renewed. The acid-soluble adenine of yeast^^ or of 

 rat liver cells^^^ was extensively renewed by glycine. Exogenous adenine-8- 

 C^"* was shown to be considerably more rapidly incorporated into the AMP, 

 ADP, and an ATP of rat Uver and other viscera (Marrian^^^), and a similar 

 result was obtained in the mouse by Bennett.^^^ Simultaneously Gold- 

 wasser-'^'^" demonstrated that these nucleotides were derived from adenine 



206 J. M. Buchanan, J. Cellular & Comp. Physiol. 38, Suppl. 1, 143 (1951). 



207 T. Korzybski and J. K. Parnas, Bull. soc. chim. biol. 21, 713 (1939). 



208 H. M. Kalckar, J. Dehlinger, and A. Mahler, J. Biol. Chem. 154, 275 (1944). 



209 H. Kalckar and D. Rittenberg, J. Biol. Chem. 170, 455 (1947). 



210 G. A. LePage, Biochem. Preparations 1, 5 (1949). 



21' W. Kiessling and O. Meyerhof, Biochem. Z. 296, 410 (1938). 



212 P. Ohlmeyer, Federation Proc. 9, 210 (1950). 



213 W. E. Cohn and C. E. Carter, J. Am. Chem. Soc. 72, 4273 (1950). 



2" D. H. Marrian, Biochem. et Biophys. Acta 9, 469 (1952); 13, 282 (1954). 



215 E. L. Bennett, Abstr. 2nd Intern. Congr. Biochem., Paris p. 197 (1952). 



216 E. Goldwasser, Abstr. 2nd Intern. Congr. Biochem., Paris, p. 200 (1952). 

 2" E. Goldwasser, Nature 171, 126 (1953). 



