metabolism of the nucleic acids 413 



3. The Kinetics of PNA Metabolism 



Several attempts have been made to elucidate the relationship between 

 the PNA's from the different parts of the cell by studying the specific 

 activities of the PNA's at different times after the administration of a 

 labeled precursor. From the work with P^^ it is clear that the initial rate of 

 uptake of isotope by nuclear PNA, in rabbit and mouse liver at least, is 

 much greater than in any of the cytoplasmic fractions,^ ■^^■^^•^^■^^ and that 

 the specific activity of nuclear PNA attains a maximum which is much 

 higher than is found with cytoplasmic PNA and is reached much earlier 

 (Figs. 1 and 2). Similarly, the activity of nuclear PNA falls off quite rapidly, 

 while that of the cytoplasmic PNA's takes some considerable time to fall. 

 The specific activities of the PNA's from the different cytoplasmic fractions 

 increase much more slowly than does that of nuclear PNA, reaching a 

 maximum about 30 hr. after administration of the isotope. The cell sap 

 differs slightly from the two particulate fractions in that the specific ac- 

 tivity of its PNA is at all times higher, while the differences between the 

 mitochondrial and microsomal PNA's are very small, particularly at the 

 longer time intervals.^ •^^•"•^^ 



The time-activity curves of the different PNA's with respect to the 

 incorporation of orotic acid-6-C^^ have been studied by Potter et al.,^°-^°^ 

 who have again found (Fig. 3) that the specific activity of the nuclear PNA 

 increases much more rapidly and reaches a much higher level than does 

 that of cytoplasmic PNA. In the cytoplasm, the curve for the mitochondrial 

 PNA was slightly lower throughout than that for the combined microsome 

 and cell sap fractions, but both curves reached a maximum about the same 

 time. Tyner et al.^^ have used glycine-2-C" as a PNA precursor in experi- 

 ments of this type. Once again, the incorporation into the nuclear PNA 

 greatly exceeded that into any of the cytoplasmic PNA's. By calculating 

 their results in absolute values, Tyner et al. have been able to relate directly 

 the incorporation of P^^ and C^^ into the adenylic and guanylic acids of the 

 different PNA's, and have observed that there is a greater uptake of P'^ 

 into the two nucleotides than of C^'' from glycine into the adenine and 

 guanine derived from them in normal liver. 



From all this work certain conclusions may be drawn: 



1. The PNA of the nucleus is much more active metabolically than the 

 PNA from any part of the cytoplasm in liver and tumor cells. 



2. In the cytoplasm, the PNA's from the mitochondria and microsomes 

 do not differ markedly from one another in their rate of renewal. 



3. The PNA of the cell sap behaves differently from either nuclear PNA 

 or that of the two particulate fractions, although qualitatively it closely 

 resembles the latter. 



4. Experiments on the incorporation of radioactive carbon into the bases 

 of the different PNA's have shown that the bases behave qualitatively in 



