metabolism of the nucleic acids 423 



2. The Degradation of the Purine Bases 

 a. The Formation and Breakdown of Uric Acid 



The initial step in the breakdown of the purine bases is one of deamina- 

 tion, the nature of the deaminases responsible having been discussed in 

 Chapter 15, and also by Christman^^ and Laskowski.'^^ 



Most tissues contain relatively little adenase (adenine deaminase) al- 

 though adenosine deaminase is more widely distributed: in contrast, 

 guanase (guanine deaminase) occurs more generally in animal tissues. 

 Adenosine may be deaminated to inosine before the sugar moiety is split 

 off, while with guanosine, the base sugar linkage may be broken before 

 deamination of the base takes place. In any event, the net result of these 

 reactions is the production of hypoxanthine and xanthine from adenosine 

 and guanosine, respectively (Fig. 4). The hypoxanthine and xanthine so 

 formed are oxidized by xanthine oxidase to uric acid, the same enzyme 

 apparently being responsible for the oxidation of hypoxanthine to xanthine 

 and of xanthine to uric acid (Fig. 4). Some doubt exists as to whether 

 xanthine oxidase is the only system concerned in the formation of uric 

 acid from xanthine and hypoxanthine, since it has been found that in rats 

 maintained on a protein-free diet there is a marked decrease in the xanthine 

 oxidase activity of the liver and to a lesser extent of the kidneys without 

 there being any major fall in the ability of the animal to oxidize xan- 

 thine.i"'i«8 



In most mammals, uric acid is not the final end-product of purine catabo- 

 lism, for it is further oxidized to the much more soluble allantoin by the 

 enzyme uricase. The exceptions to this general rule are man, other primates, 

 and the- Dalmatian dog (for recent reviews, see Christman^^ and Franke^*). 

 The anomal}^ in the metabolism of uric acid by the Dalmatian coach-hound 

 has been the subject of much research, from which it appears that the 

 uricase content of the livers of Dalmatian and other dogs is similar^^^ 

 and that the excretion of uric acid by the former is not due to an inability 

 of the animal to convert uric acid to allantoin, but rather to an abnormality 

 of kidney function. Friedman and Byers"" consider that the kidney of the 

 Dalmatian dog can clear uric acid more rapidly than can that of other dogs 

 but that there is little tubular reabsorption. Wolf son et al.,"^ on the other 

 hand, believe that there is active tubular excretion of uric acid in the kidney 

 of the Dalmatian dog as distinct from other breeds. 



The oxidation of uric acid to allantoin (Fig. 4) has been extensively 



1" J. N. Williams, P. Fiegelson, and C. A. Elvehjem, J. Biol. Chem. 185, 887 (1950) • 

 1^* A. D. Bass, J. Tepperman, D. A. Richert, and W. W. Westerfeld, Proc- 



Soc. Exptl. Biol. Med. 73, 687 (1950). 

 1" F. W. Klemperer, H. C. Trimble, and A. B. Hastings, /. Biol. Chem. 125, 445 (1938). 

 I'o M. Friedman and S. O. Byres, J. Biol. Chem. 175, 727 (1948). 

 171 W. O. Wolfson, C. Cohn, and C. Shore, J. Exptl. Med. 92, 121 (1950). 



