628 URIC-ACID METABOLISM AND GOUT 



Properties of Uric Acid. — Uric acid, when pure, is white, and crystallizes in 

 rhombic tablets. Its solubility is very slight; at room temperature (18°) it dissolves 

 but about one part to 40,000 of water, so that a saturated solution contains but 

 0.0253 gram to the liter. It is much more soluble in blood-serum, dissolving in 

 1000 parts,' probably held in some complex combination. His and Paul have 

 shown that in a saturated solution only 9.5 per cent, of the molecules are disso- 

 ciated, the dissociation occurring in two steps; the first and chief dissociation is 

 into H and C.SH3N4O3, which then undergoes further dissociation into H and 

 C5H2N4O3, the latter dissociation being very slight. If any other acid is present 

 in -the solution, its dissociation and liberation of free hydrogen ions interferes with 

 the dissociation of the uric acid, and as the undissociated uric acid is extremely 

 insoluble, the amount dissolved in an acid solution is much less than in a neutral 

 solution.^ 



Gudzent^ found that saturated solutions of urates gradually precipitate out the 

 salts because of a transformation of part of the uric acid into what he believes to 

 be a lactirn form. (The lactim form is shown in the following formula, as com- 

 pared with the isomeric lactam form shown above, in which uric acid is supposed 

 to exist ordinarily.) 



N=C— OH 

 I I 

 HO— C C— NH 



\ 

 C— OH 



/- 



N— C— N 



(Lactim form of uric acid) 



With alkalies uric acid yields two series of salts, corresponding to these two 

 steps in dissociation: one, in which one atom of the base enters, is called the 

 biurate or monobasic urate; the other is the so-called "neutral" or bibasic urate. ^ 

 Of the two, the latter is much the more soluble. The monosodiumtirate forms 

 colloidal solutions in water, from which the crystalline salt gradually falls out. 

 The quadriurate, of which much was said in the earlier literature, probably does 

 not exist (Kohler).' 



In the urine the uric acid and the urates are kept in solution by the phosphates, 

 the disodium phosphate preventing the decomposition of the urates into uric acid by 

 the acid salts of the urine. Possibly other constituents of the urine, especially 

 the pigments and NaCl, also aid in its solution. Urine may form quite stable 

 supersaturated solutions and Kohler states that the urine is a truly supersaturated 

 solution of sodium urate. How the uric acid is kept in solution in the blood is not 

 exactly understood, but Gudzent believes that uric acid can exist in the blood only 

 as the monosodium urate, and in the less soluble but more stable lactim form, which 

 is soluble only to the extent of 8.3 mg. per 100 c.c. .serum (the lactam form being 

 soluble up to 18 mg.). However, amounts over 20 mg. per 100 c.c. have been 

 detected in the blood of nephritics; here solution may have been aided by the 

 other retained metabolites. Bechhold' and others have maintained that urates 

 may be present in the blood in a colloidal state which cannot pass out through 

 the kidneys. 



FORMATION OF URIC ACID^' 



The origin of uric acid is chiefly, although not exclusively, from the 

 nucleoproteins, and it is customary to refer to uric acid formed from 

 the nucleoproteins of the foods as ''exogenous'' uric acid, in contrast 



» Taylor, Jour. Biol. Chem., 1906 (1), 177. 



* Concerning the solubility of uric acid in urine see Haskins, Jour. Biol. Chem., 

 1916 (26), 205. 



" Zeit. physiol. Chem., 1909 (60), 38. 



" As a matter of fact, both salts give a slightly alkaline reaction when dis- 

 solved in water (Taylor). 



'Zeit. physiol. Chem., 1911 (72), 169; 1913 (78), 205; Zeit. klin. Med., 1919 

 (87), f 338. 



» Biochem. Zeit., 1914 (64), 471. 



» See review in International Clinics, 1910, XX d), 76. 



