250 BIOCHIMICA ET BIOPHYSICA ACTA VOL. 12 (1953) 



THE ROLE OF PHOSPHOGLYCOSYL COMPOUNDS 

 IN THE BIOSYNTHESIS OF NUCLEOSIDES AND NUCLEOTIDES 



by 



HERMAN M. KALCKAR 

 Universitetets Institut for Cytofysiologi, Copenhagen {Denmark) 



Our growing understanding of the function of inorganic phospfiate in biological 

 synthesis stems back to the early discoveries of Arthur Harden and Otto Meyerhof. 

 The coupling of the phosphate uptake with carbohydrate metabolism is of two essentially 

 different types. The first type of coupling, with oxido-reductive processes, remained a 

 mystery until Otto Warburg and his group in 1939, having isolated the crystalline 

 enzyme as well as the pure coenzyme system of phosphotriose oxidation, were able to 

 identify the primary product of phosphate coupling as 1,3-diphosphoglyceric acid. This 

 was the first acylphosphate discovered in biological systems. From the work of Lipmann, 

 Lynen and Racker we know now that the primary attack of orthophosphate in the 

 coupled oxidations is a fission of an acyl mercapto linkage. Thus the carbonyl groups 

 in phosphoglyceraldehyde or in pyruvate do not react directly with phosphate. The 

 sequence of reactions seems to start with a complex between the carbonyl group and a 

 coenzyme mercapto (SH) group. This complex is oxidized and the resulting acyl complex 

 undergoes enzymic fission, orthophosphate (or pyrophosphate) yielding acylphosphate and 

 a free mercapto group. 



The second type of coupling involves a more direct reaction between phosphate 

 and a substituted aldehyde group and was described by Carl and Gerty Cori in 1937, 

 when they discovered the phosphorolytic fission of the i-4glycosidic linkages of glycogen. 

 This type of phosphorolytic fission, which is readily reversed, was shown by Doudoroff 

 and co-workers to play a role in the synthesis of many disaccharides. The primary 

 product formed in enzymic phosphorolysis of glycosidic linkages is a pliosphoglycosyl 

 compound, and these i-estcrs can exchange their phosphate group enz3'matically with 

 a sugar. The work on the phosphorolytic fission of the glycosidic linkages of di-and poly- 

 saccharides turned out to be of importance as well for a close understanding of many 

 features in nucleoside and nucleotide metabolism. The present article deals with some 

 recent work on the importance of phosphogiycosyl compounds in nucleoside and nucleo- 

 tide biosynthesis. 



Nucleoside phosphorylases. The building blocks of nucleic acids contain an N-ribosyl 

 linkage. It was found that nucleoside phos])horylase, an enzyme isolated from mammalian 

 liver, brings about a liberation of i)hosphoribosyl or deoxyribosyl groups^- ^. The phos- 

 phopentosyl compounds react readily with nitrogenous bases to form nucleosides. 



References p. 263J264. 



