622 URIC-ACID Mf-rri HOLISM axd gout 



It will be seen that this proposed formula postulates in the nucleic 

 acid molecule, one radical of each of the two purines and pyrimidines, 

 eacli of these ho'mg iniited by a carbohydrate radical to a i)hosphoric 

 acid radical. Reco<:-nizing that tliis must be looked upon as a provi- 

 sional fonnula,"'' it will serve as a base of departure from which to 

 consider the metabolism of nucleic acid. 



The groupin<r of hexose -\- purine or hexose -|- pyrimidine is re- 

 ferred to as a "luicleoside," analogous in terminology to "glueoside." 

 The same groupings plus the phosphoric acid radical constitute the 

 "nucleotids, " nucleic acid thus being made up of four nucleotids. 

 Emil Fischer has reported ~^ the synthetic production of a nucleotid, 

 composed of pliosj^horic acid united to a glucoside of theophyllin, this 

 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 believe 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 split 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 believej 

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

 tack each bond. One enzyme separates the pliosphoric acid radical 

 from the nucleoside, thus : | 



HjPO, - C.HA - C,H,N50 + H.O >- H^PO, + C,,H ,0, - C,H,N,0 



guanylic acid phospho-nuclease guanosine 



and this enzyme is therefore designated as jjhospho-nuclcasc. 



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

 cal, thus: 



HjPO, - C,H,03 - r,H,N,0 + 11,0 y ILPO, - C,HA. + C.HiN^O 



guanylic acid i)uriiie-nuclease guanine 



Following either of these cleavages, the enzymes which deaminize 

 l)ui-ijies ])egin to act, and we have formed as a result either the free 

 oxypurines or the oxy purines still boimd in the glucoside-like combi- 

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



■:> Jdiu's and ITcad (Jour, l^iol. Clicni., 1!)17 (2!>), 11]) liavo advanced evidence 

 to indicate* that tlie liid<af,'e between tlie neiiclent ids is between the earhojiydrate 

 radicals rather than between the ])h(»s|)]u)ric acid jri^onps. 



7b Sitzungsbcr. k. Akad. Wissensch., J^erlin, 1*114 (IJ.'?), DOf). 



