HANS KLENOW 



phosphate, glucose- i,6-diphosphate, and phosphoglucomutase a ribose phosphate 

 has been isolated, the properties of which suggest it to be ribose- 1,5-diphosphate. 



The final proof that this compound is an intermediate in mono-nucleotide forma- 

 tion is, however, still lacking. Most recently a completely new type of pentose phos- 

 phate ester, important for these systems, has been isolated. These important findings 

 were obtained from experiments on 6-carboxy-uracil, also called orotic acid, which 

 is known to be the precursor of the uracil of nucleic acids. Kornberg (1954) found 

 that orotic acid could be incorporated into a nucleotide by an enzyme system which, 

 as in the foregoing cases, involved an activation of ribose-5-phosphate by adenosine 

 triphosphate; he identified the activated form as 5-phospho-ribosyl-i -pyrophosphate. 

 Whether this reaction proceeds in one step, i.e. consisting of a transfer of pyrophos- 

 phate from adenosine triphosphate to ribose-5-phosphate, or in two steps having 

 ribose- 1,5-diphosphate as an intermediate, still has to be seen. 



With the 5-phospho-ribosyl- 1 -pyrophosphate the formation of the 5 '-mononucleo- 

 tide of adenine has been demonstrated to proceed as follows : 



5-phospho-ribosyl- 1 -pyrophosphate -1- adenine % 5 / -adenylate + pyrophosphate. 



Likewise orotic acid gave rise to orotodylic acid with the same reaction mechanism. 

 The enzymes responsible for these reactions have been found in pigeon-liver 

 acetone powder and in yeast. Thus this interesting new reaction for nucleotide 

 formation is a reversible pyrophosphorolytic cleavage of the 5 / -nucleotides. The 

 establishment of this reaction might very well lead to the explanation of the 

 enzyme reaction responsible for the synthesis of the imidazole and the pyrimidine 

 rings of the purines. It has been found that in the case of inosinic acid the purine 

 synthesis is completed only after introduction of ribose phosphate into the precursors 

 (Greenberg, 1953). The formation of the nucleotides of these precursors might occur 

 through Kornberg's new ribose phosphate ester as intermediate. In that case it 

 might be possible to synthesize purine precursor ribotides enzymatically and with 

 these to study the reactions which lead to completion of the purine rings. 



Thus we have now accounted for some enzyme reactions by which ribose may be 

 formed and for pathways for the formation of some ribosides and ribotides from 

 ribose-phosphate esters and the appropriate purines and pyrimidines. How these 

 nucleotides are linked together to form the nucleic acids is obviously a most appealing 

 problem. No experimental evidence on this problem is yet in existence, but extremely 

 stimulating theories have recently been advanced (Kalckar, 1953). 



REFERENCES 



Benson, A. A., Bassham, J. A. and Calvin, M. (1951). J. Amer. chem. Soc. 73, 2970. 



Bernstein, I. A. (1953). J. biol. Chem. 205, 317-329. 



Bloom, B., Stetten, M. R. and DeWitt Stetten jr. (1953). J. biol. Chem. 204, 



681-694. 

 Brawerman, G. and Chargaff, E. (1953). J. Amer. chem. Soc. 75, 41 13. 

 Brown, G. B., Roll, P. M., Plentl, A. A. and Cavalieri, L. F. (1948). J. biol. 



Chem. 172, 469-484. 



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