120 S. S. COHEN 



Both purine and pyrimidine analogs are known to enter RNA. These 

 include purines, such as 8-azaguanine and 8-azaadenine, and pyrimidines, 

 such as 2-thiouracil. 8-Azaguanine was first shown to enter the RNA of 

 tobacco mosaic virus (Matthews, 1953) and was subsequently observed to 

 be incorporated into the RNA of bacteria, mouse organs, and tumors 

 (Lasnitzki et al., 1954). Particles of tobacco mosaic virus containing the 

 unnatural base appear to be noninfectious and a comparable result has been 

 observed for virus particles which have incorporated thiouracil in their RNA 

 (Jeener and Roseels, 1953; Jeener, 1956). The RNA of B. cereus which has 

 incorporated azaguanine (Matthews and Smith, 1956) was found to contain 

 a number of relatively short polynucleotide chains in which the proportion 

 of the unnatural purine was high, particularly so at the end of the chains. 

 Similarly, the distribution of 2-thiouridyHc acid in the virus RNA indicated 

 that it tends to be concentrated at the end of polynucleotide chains, and at 

 one end more than the other {Msmdeletal., 1957a). The incorporation of small 

 amounts of azaguanine into DNA has recently been recorded for B. cereus 

 (Mandel et al, 1957b), but not for the DNA of E. coli or T2 bacteriophage 

 (Smith and Matthews, 1957). 



Mention has already been made of the incorporation of unnatural amino 

 acids into proteins, even as unnatural substances, such as acetyl pyridine, 

 may replace nicotinamide in an enzymatic system to generate unnatural 

 pyridine nucleotide coenzymes (Kaplan et al., 1954) or the toxic fluoroacetate 

 can form the toxic fluorocitrate (Peters, 1957), capable of jamming the tri- 

 carboxylic acid cycle. It is possible to fool an enzyme with an analog but the 

 resulting unnatural product is rarely capable of maintaining the deception 

 with many enzymes and fulfilling a normal function. One apparent exception, 

 j8-galactosidase containing selenomethionine (Cohen, G. N., and Cowie, 1957) 

 is produced to not quite a degree of activity as the enzyme containing normal 

 methionine, although it is not known if this reflects an inefficiency in enzyme 

 production or an inherently low enzymatic activity when selenium is built 

 into the protein. 



G. Problems of Turnover 



1. Proteins 



Until relatively recently, it was believed, as a result of the work of Borsook 

 and Keigliley (1935) and of Schoenheimer (1942), that all proteins in the 

 mammalian organism were being constantly broken down and resynthesized 

 at various rates. This situation was also apphcable to most other chemical 

 components of mammal tissue and was termed "the dynamic state of body 

 constituents." Re-examination has demonstrated that most of this turnover 

 of protein can be attributed to proteins of the viscera (Borsook, 1950). 



