278 PETER REICHARD 



glycine,^ -^ aspartic^ and glutamic^ acids, and pyruvate* thus increased the 

 daily output of uric acid and were considered to be possible precursors. 

 Arginine and histidine have also been discussed as possible precursors, 

 mainly because of their similarity to the purines in structure, but also be- 

 cause of a report by Ackroyd and Hopkins^ that rats excreted a diminished 

 amount of allantoin when put on a diet deficient in these amino acids. 

 Allantoin is the end-product of purine cataboUsm in the rat (see Chapter 

 26). 



As Lennox^ has pointed out, all these experiments suffered from the 

 general defect that during the fasting period retention of uric acid by the 

 animal occurred; the uric acid could then be released by the ingestion of 

 the substance under test. The introduction of the isotope technique into 

 this field has made it possible to reinvestigate the problem. Experiments 

 by Bloch and Schoenheimer^ with arginine-N^^ proved that the amidine 

 group of this amino acid was not a precursor of allantoin in the rat. Nega- 

 tive results were also obtained by Barnes and Schoenheimer'' with urea-N^^, 

 by Tesar and Rittenberg* with histidine-7-N'*, and by Plentl and Schoen- 

 heimer' with uracil-N^^ and thymine-N'^. 



Schuler and Reindel'" found that pigeon liver slices accumulate a purine- 

 like substance which can be transformed into uric acid by kidney slices. 

 Edson et a/." identified this substance as hypoxanthine and showed that 

 pigeon liver lacked xanthine oxidase, which was present in kidney slices. 

 These authors furthermore found that the synthesis of hypoxanthine was 

 increased by the addition of lactic and pyruvic acids to the medium. Later 

 Orstrom et al.^^ showed that added oxalacetate and glutamine also had a 

 stimulating effect. Because of the complexity of the system involved, 

 no definite conclusions were drawn, but the possibility of glutamine acting 

 as an "ammonia carrier" was considered. 



(1) Carbon Precursors. The fundamental work on the carbon precursors 

 of the uric acid excreted by pigeons was carried out by Buchanan and co- 

 workers. ^^'^^ In their experiments simple metabolically important C'*- 



2 A. A. Christman and E. C. Mosier, J. Biol. Chem. 83, 11 (1929). 



3 H. V. Gibson and E. A. Doisy, J. Biol. Chem. 55, 605 (1923). 

 * H. Ackroyd and F. G. Hopkins, Biochem. J. 10, 551 (1916). 



6 W. G. Lennox, J. Biol. Chem. 66, 521 (1925). 



6K. Bloch and R. Schoenheimer, J. Biol. Chem. 138, 167 (1941). 



7 F. W. Barnes, Jr., and R. Schoenheimer, J. Biol. Chem. 151, 123 (1943). 



8 C. Tesar and D. Rittenberg, J. Biol. Chem. 170, 35 (1947). 



« A. A. Plentl and R. Schoenheimer, J. Biol. Chem. 153, 203 (1944). 

 i» W. Schuler and W. Reindel, Z. physiol. Chem. 221, 209 (1933). 

 " N. L. Edson, H. A. Krebs, and A. Model, Biochem. J. 30, 1380 (1936). 

 »2 A. Orstrom, M. Orstrom, and H. A. Krebs, Biochem. J. 33, 990 (1939). 

 "J. C. Sonne, J. M. Buchanan, and A. M. Delluva, /. Biol. Chem. 166, 395 (1946). 

 " J. M. Buchanan and J. C. Sonne, J. Biol. Chem. 166, 781 (1946). 



