630 URIC-ACID METABOLISM AND GOUT 



really constituting the long-sought synthesis of a nucleic acid, even 

 though the artificial product is not the same as any known to occur in 

 nature. With these facts before us we may consider the manner in 

 which nucleic acids are disintegrated in the animal body. 



So large a molecule can conceivably be disintegrated in many differ- 

 ent ways; that is, the lines of cleavage might pass through several 

 different points and in many different orders, but there is evidence 

 available which causes us to beheve that the process is quite constant 

 in animal metabolism. Jones considers it probable that the first step 

 is a decomposition of the tetranucleotid into dinucleotids, and that 

 these are in turn spKt into mononucleotids. Little is known about the 

 subsequent career of the two pyrimidine nucleotids, but we have an 

 abundance of information concerning the nucleotids containing the 

 purines, and it is in these our present interest lies. Each nucleotid 

 has two points at which it might be split, and we have reason to believe 

 that there exist in animal tissues enzymes which may specifically at- 

 tack each bond. One enzyme separates the phosphoric acid radical 

 from the nucleoside, thus: 



H2PO4-C6H8O3-C5H4N5O + H2O ^H3P04 + C5H9O4-C6H4N6O 



guanylic acid phospho-nuclease guanosine 



and this enzyme is therefore designated as phospho-nuclease. 



Another enzyme, purine nuclease, splits off, instead, the purine radi- 

 cal, thus: 



H2PO4 - CsHsOs - C5H4N6O + H2O > H.,P04-C6H904 + CsHsNsO 



guanylic acid purine-nuclease guanine 



Following either of these cleavages, the enzymes which deaminize 

 purines begin to act, and we have formed as a result either the free 

 oxypurines or the oxypurines still bound in the glucoside-like combi- 

 nation with sugar. If the purines are free the reaction will be : 



C6H5N5O + H2O > C6H4N4O0 + NH3 



guanine guanase xanthine 



or, in case the guanine glucoside is present: 



C5H9O4 - C6H4N5O + H2O — » C6H9O4 - C6H3N4O2 + NH 



guanosine guanosine-deaminase xanthosine 



In the latter case a hydrolytic enzyme, xanthosine-hydrolase, then 

 splits off the xanthine, so that by either route the end result is the same. 

 By a similar series of changes the adenine radical is converted into 

 hypoxanthine, either directly by adenase: 



CsHsNc + H2O > C6H4N4O + NH3 



adenine adenase hypoxanthine 



or by adenosine-deaminase the hypoxanthine-glucoside (inosine) is 

 formed, and later the hypoxanthine is split off. 



