252 H. M. KALCKAR VOL. 12 (1953) 



glucose-i-phosphate^^. Whether there may be a single inversion, a double inversion or no 

 inversion at all, is at the present stage impossible to predict, especially for ribosides. 



Specificity of the nitrogenous bases. The fact that the phosphorolysis of the purine 

 and pyrimidine nucleosides is not catalyzed by the same enzyme has been established 

 beyond any doubt (Deutsch and Laser^^, Klein^^, Manson and LampenI"). Paege 

 AND ScHLENCK^' havc described a pyrimidine nucleoside phosphorylase present in 

 E. coli which is specific for uridine. As to the question whether the same enzyme can 

 catalyze the phosphorolysis of ribosides and deoxyribosides, or whether two enzymes 

 are required, nothing definite can be stated. Studies on rat liver purine nucleoside 

 phosphorylase might indicate a common enzyme for the two pentoses^; the behaviour of 

 bacterial enzymes indicats that here two independent enzymes may be operating^^- 1^. 



The specificity of the liver purine nucleoside phosphorylase with respect to the 

 nitrogenous aglycone is very unpredictable. Hypoxanthine and guanine ribosides or 

 deoxyribosides are swiftly phosphorolyzed. The corresponding xanthine compounds 

 react very slowly, however, and the synthesis of the corresponding purines is of the 

 same order with respect to rate. 



Surprisingly enough adenine is not an active participant in nucleoside phosphoryla- 

 tion ; correspondingly a direct phosphorolytic fission of adenosine does not occur, and the 

 attack on this compound is preceded by a deamination of adenosine to inosine. An 

 exception to these observations has recently been reported. E. coli contains an enzyme 

 which specifically catalyzes the phosphorolysis of adenosine^^. 



Purine derivatives as antigroiuth factors and mutagens and their relation to nucleoside 

 phosphorylase. Amongst the many unpredictable facts concerning the specificity of this 

 enzyme is the finding by Friedkin^" that 8-azoguanine, incubated with ribose-i -phos- 

 phate or deoxyribose-i-phosphate in the presence of liver nucleoside phosphorylase, 

 gives excellent yields of the corresponding azoguanine nucleosides. Accordingto Kidder^^ 

 8-azoguanine is a strong antigrowth factor for Tetrahymena gelii, a micro-organism which 

 requires guanine as a growth factor. Also certain tumors are inhibited by azoguanine-^ 

 Friedkin's findings raise the problem as to whether the participation of azoguanine in 

 nucleoside (or nucleotide) metabolism can account for the suppression of growth. The 

 enzymatically formed azoguanine ribosides were assayed by Kidder for growth inhibi- 

 tion on Tetrahymena gelii and were found to exert, on a molar basis, half the inhibitory 

 effect of free azoguanine. A detailed study of the incorporation of azoguanine into 

 nucleotides and nucleic acids (bypassing of nucleosides ?) has not yet been performed, 

 but experiments using isotopically labelled azoguaninc^^ lend support to the theory^^ 

 that this substance can give rise to the formation of abnormal nucleotides and nucleic 

 acids. The author of the present review is, however, inclined to bring up another aspect 

 which might help to interpret the data collected on the effect of azoguanine on the 

 growth of certain mammary carcinoma in mice^^. Friedkin's experiments show that 

 azoguanine forms ribosyl or deoxyribosyl compounds very effectively. This could imply 

 that under conditions (or in certain types of tumors) where the availability or the rate of 

 formation of ribosyl (espec. deoxyribosyl) is such as to barely suffice for rapid growth, a 

 side tracking by azoguanine will manifest itself biologically. The conditions hinted at 

 could be rapid expansive growth during which the rate of biosynthesis of pentosyl in 

 general becomes a limiting factor. If azoguanine acts like a ribosyl or deoxyribosyl trap 

 it would greatly inhibit growth under such circumstances. The same type of effect may 

 play a role for the antimutagenic effect of guanosinc, inosine and adenosine (NoviCK 

 References p. 263I264. 



