lOO J. N. DAVIDSON 



much less pronounced extent by muscle extracts. The polymerase used 

 in most of these tests has been purified from Ehrlich ascites tumour cells 

 but polymerases from spleen thymus and bone marrow are likewise affected. 

 The interfering factors are thermolabile, acid-precipitable and non- 

 dialysable but so far have not been identified with any known enzyme or 



TABLE IV 



Inhibition of Enzymes by Fractions Prepared from Extracts of Normal 



Rat Liver 



Inhibition of 



TdR TMP ^ , 



Fraction kinase kinase Polymerase 



A + + + 



B ± + — 



C — + + 



D — — + 



enzymes. They appear to be different from the enzymes which hydrolyse 

 the deoxyribonucleoside triphosphates with the release of inorganic 

 phosphate. The distribution of the interfering substances in various 

 tissues suggests that different factors are involved in the inhibition of the 

 various enzymes and this has been confirmed by fractionation of liver 



AMP -■ ♦dAMP— ^dATP 



Glycine 1 



Glutamine — ^IMP 

 Asp. etc. I 



GMP -.-dGMP ^dG 



Aspartate Carbamyl 



X phosphate 

 / CTP--^CDP— ►dCDP-j^dCTP 



Ureidosuccinate UTP dCMP 



i f / 



Orotate-^OMP— »-UMP---»dUMP — *-TMP— :^TTP 



Fig. 3. Pathways involved in the biosynthesis of DNA. 



extract with purification and separation from each other of the factors 

 inhibiting TdR kinase, TMP kinase and the polymerase [15] (Table IV). 

 Kinase inhibitions so far discussed have referred to the system pro- 

 ducing TTP. The pattern of results obtained with the kinases for dAMP, 

 dGMP and dCMP is quite different in that these enzymes in ascites cell 

 extracts are not inhibited by extracts of normal liver. The kinase system 

 for producing TTP would accordingly appear to be unique both in its 



