VOL. 12 (1953) BIOSYNTHESIS OF NUCLEOSIDES AND NUCLEOTIDES 



257 



The significance of phosphoribomutase in analogy with phosphoglucomutase*^ 

 was first clearly recognized by Schlenk^*. Later Manson and Lampen found that 

 deoxyribosides can be converted to deoxyribose-5-phosphate. Klenow and Larsen 

 found that phosphoribomutase from muscle and yeast*^ can be activated by small 

 amounts of synthetic a-glucose-i,6-diphosphate. It should be added that the muscle 

 ribomutase requires an activator only in the presence of 8-hydroxyquinoline. A clue to 

 the understanding of the nature of activation of phosphoribomutase was given by the 

 following type of reaction : 



ribose-i-phosphate + a-glucose-i,6-diphosphate ^ 



ribose-i,5-diphosphate + glucose-6-phosphate 



This reaction, which is analogous to Leloir's reaction between a-glucose-i,6-diphosphate 

 and mannose-i-phosphate'^®, can be pushed towards the right (and be demonstrated 

 optically) by addition of "Zwischenfermenf' and triphosphopyridine nucleotide (TPN) 

 in the presence of which the glucose-i-phosphate is oxidized^^. The new diester, which 

 was isolated by means of chromatography on a Dowex-i column, has a strong cofactor 

 activity in the phosphoribomutase test. Table V lists some of the properties of ribose- 

 1,5-diphosphate. It will be noticed that although the i-ester phosphate is acid labile 

 it is not as labile as ribose-i-monophosphate. 



TABLE V 



STABILITY OF I-ESTER P 



Synthetic preparation (courtesy Prof. Posternak) . 

 * Synthetic preparation (courtesy Prof. A. R. Todd). 



With the knowledge about formation and properties of ribose-i,5-diphosphate in 

 mind, Saffran and Scarano were in a position to furnish further evidence for ribose- 

 1,5-diphosphate as the ester which reacts with radioactive adenine yielding 5-adenylic 

 acid. First of all they showed that incorporation of adenine can be increased just as much 

 by preincubation of ribose-i-phosphate with a-glucose-i,6-diphosphate (synthetic, 

 Posternak) as with the former and ATP. Secondly the ribose ester formed after these 

 preincubations possesses the properties described by Klenow. It remains to study the 

 reaction between ribose-i,5-diphosphate and adenine in more detail in order to prove 

 that we are here in fact dealing with a simple nucleotide glycosylphosphorylase. 



The role of ribose-i,5-diphosphate is probably not limited to the function as a co- 

 phosphoribomutase and as an exchange substance for adenine and hypoxanthine. It 

 may also be the substance which reacts with nicotinamide (c/. Leder and Handler^^), 



References p. 263J264. 



