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



uracil for nucleic acid synthesis, labelled uracil can be detected in 5-uridylic compounds*''. 

 It has, moreover, been found that addition of penicillin causes the staphylococci to cut 

 down on the incorporation of uracil into ribonucleic acid with a corresponding increased 

 incorporation in the derivatives of 5-nucleotides^'*. It seems likely therefore that the 5- 

 nucleotides, their polyphosphates or other derivatives are precursors of nucleic acid 

 units, especially those of ribonucleic acids. As discussed earlier in this review the incor- 

 poration of nitrogenous bases for nucleic acid synthesis is complex. Nucleosides are 

 mainly b3^passed and it seems that in the case of Lactobacillus helveiicus which needs 

 uracil, more complex nucleotides than the simple 5-nucleotides are needed^^. One could 

 well image thatUTP, reacting with free nucleosides or nucleosides bound as end-groups 

 in a ribonucleic acid chain, could form nucleic acid linkages through pyrophosphorolysis. 

 In other words it seems worthwhile to search for uridyl transferases in which nucleosides 

 or end-groups of nucleic acids can be used as urid} 1 acceptors. 



As usual, progress in this field depends on the development of new, ingenious and 

 bold methods, especially of the kind with which Otto Warburg has provided us to 

 such a generous extent. 



ACKNOWLEDGEMENT 



The studies on nucleotide metabolism performed in Universitets Institut for Cyto- 

 fysiologi have been supported by grants from the following foundations : Carlsbergfon- 

 det, Lederle Laboratories, American Cyanamid Company, Institute Sieroterapico Itali- 

 ano, Nordisk Insulinfond, The Rockefeller Foundation and The Williams Waterman 

 Fund of The Research Corpoiation. 



Addendum (July 8, 1953) 



In our laboratory Scarano (unpublished work) has recently isolated an enzyme 

 from pigeon liver, phosphoribokinase, which catalyzes the phosphorylation of ribose- 

 5-phosphate in the i-position, yielding ribose-i,5-diphosphate. ATP is phosphoryl donor. 

 The fractionated enzyme was freed from phosphoribomutase and consequently ribose- 

 I -phosphate does not serve any more as a phosphate acceptor. Adenine is the only 

 nitrogenous compound which reacts rapidly with the ribose-i,5-diphosphate in the heated 

 fraction of the pigeon liver homogenate after high-speed centrifugation. 



SUMMARY 



In the biosynthesis of nucleosides and nucleotides the intermediate formation of ribosc (or 

 deoxyribose)- 1 -phosphate and their corresponding 5-esters may play a prominent role in the animal 

 organism ; the pathway seems to involve a phosphorylation (by ATP) of the i position of ribose- 

 5-phosphate yielding ribose-i,5-diphosphate. This new dicster can also be obtained from ribose- 

 i-phosphate and glucose-i,6-diphosphatc in the presence of phosphoglucomutase. In pigeon liver 

 extracts there are strong indications that ribose-i,5-diphosphate can exchange its i-cster phosphate 

 with adenine, hypoxanthine or incomplete purine precursors. 



Glucose-i-phosphate and galactose- i-})hosphate (both a-glycosyl compounds) also play a role 

 as acceptors of uridyl radicals catalyzed by a special class of enzymes, uridyl transferases. I'ridine 

 triphosphate plus one of these enzymes incubated with one or the other of the two above-mentioned 

 i-esters yields Leloir's UDP-glucosc or UDP-galactose, the so-called "CoWaldcnases". 



Conversely, the latter compound incubated with inorganic pyrophosphate and a uridyi- 

 transferase gives rise to the formation of uridine triphosphate (UTP). UTP may, through the action 

 of another uridjd transferase, play a role in the incorporation of the uridyl radical into nucleic acids. 



References p. 263I264. 



