382 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



although with rat liver slices'*^ glycine-N'^ yielded ratios definitely greater than 1, 

 which indicates differences between these systems and the intact animal. 



The relative independence of the two pathways in the rat is illustrated 

 by the influence of exogenous adenine in "sparing" de novo adenine from 

 glycine^* or formate^^ to a somewhat greater extent than de novo guanine 

 (cf. Table IV, hues 7 vs. 6, particularly the values for liver, and Table II, 

 column 8 vs. columns 9 and 10). Also, when synthesis de novo was largely 

 abolished by a folic acid antagonist, the relative amount of guanine derived 

 from exogenous adenine was considerably increased. ^^ If a compound is 

 incorporated into one of the pathways after a point of bifurcation, the ex- 

 tent to which it reaches the other pathway is dependent upon the reversi- 

 bility of steps back to some intermediate common to a bridge pathway, and 

 this reversibility may vary with physiological conditions of the tissues and 

 the relative demand for the products of each pathway. 



A derivative formed from 2 , 6-diaminopurine must be, or be readily con- 

 verted into, a member of either the pathway between the common in- 

 termediate and the "active" guanine (or of the bridge pathway between the 

 "active" derivatives); the incorporation of diaminopurineintoa phosphoryl- 

 ated derivative of 2 , 6-diaminopurine riboside has been observed in the 

 mouse."" 4-Amino-5-imidazolecarboxamide^^ may be incorporated earlier 

 in the assembly line. Certain exogenous purine nucleosides^^ and nucleo- 

 tides^^ '^^ can also be converted into the "active" derivatives. 



c. Pyrimidine Derivatives 



The pyrimidine derivatives require a scheme similar to that in Fig. 5, 

 although the problem of interconversion is the simpler one of amination or 

 deamination. Provision must be made for the incorporation of orotic acid," 

 including its ready conversion into soluble uridine-5'-phosphate deriva- 

 tives,"^ and for a direct incorporation of each nucleoside and nucleo- 



tide.24.28,64 



Little can be said with certainty regarding pathways of biosynthesis 

 peculiar to DNA. Evidence can be cited to support most of the logical pos- 

 sibilities: a direct deoxygenation of a ribose to a deoxyribose derivative,^^'®* 

 and for an independent origin of deoxyribose"""^ (Chapter 22) or of de- 



'63 P. Reichard and S. Bergstrom, Acta Chem. Scand. 5, 190 (1951). 



170 G. P. Wheeler and H. E. Skipper, Federation Proc. 12, 289 (1953). 



i7> R. B. Hurlbert, Federation Proc. 12, 222 (1953). 



'" E. Racker, in "Phosphorus Metabolism" (McElroy and Glass, eds.), Vol. 1, p. 145. 



Johns Hopkins Press, Baltimore, 1951. 

 '" S. S. Cohen, in "Phosphorus Metabolism" (McElroy and Glass, eds.), Vol. 1, p. 



148. Johns Hopkins Press, Baltimore, 1951. 

 17^ M. G. McGeown and F. H. Malpress, Nature 170, 575 (1952). 



