ALKAPTONURIA 587 



found in the blood but not in the feces of alkaptonurics, and the urine 

 shows no other deviations from the normal except a slight increase in 

 ammonia, with which the acid is combined. It is of ran; ocj'urrence. 

 persists throughout life with but little apparent effect upon the health 

 of the individual, and is often hereditary, being grouped by Clarrod 

 along with cystinuria, pentosuria and albinism as a "chemical malfor- 

 mation " of hereditary origin.^" The relation of these aromatic bodies 

 to the aromatic constituents of the proteins is best shown by comparing 

 their structural formulae : 



Phenylalanine, / NcH,— CHNHj— COOH. 



Tyrosine, HO^ \CH2— CHNH,— COOH. 



_0H 

 Uroleucic acid,^i / NcHa— CHOH— COOH. 



H0~ 

 _0H 

 Homogentisic acid, <^ y CH-. — COOH. 

 H0~ 



Apparently the condition depends upon an abnormality in the inter- 

 mediary metabolism, and not upon an abnormal formation of homo- 

 gentisic acid through intestinal putrefaction, as was at first believed. 

 Alkaptonuria is never observed in slight degrees; if there is any 

 homogentisic acid in the urine at all it is there in large amounts (4-5 

 grams per day), depending on the diet, for when the error in metabo- 

 hsm is present at all it is complete. On a mixed diet the ratio of 

 homogentisic acid to nitrogen in the urine is 40-50 to 100. The pre- 

 vailing idea has been that the abnormality consists not in the excessive 

 formation of homogentisic acid, but in a lack of ability on the part 

 of the alkaptonuric individual to split open the benzene ring. It is 

 generally stated that tyrosine and phenylalanine first suffer a splitting 

 out of the nitrogen radical from the alanine side-chain, and then are 

 oxidized into homogentisic acid, following which changes comes a 

 disintegration of the benzene ring, with subsequent complete oxidation. 

 On this basis the alkaptonuric accomplishes the conversion into the 

 oxj'-acid but the process stops there. Wakeman and Dakin,"'- how- 

 ever, have obtained evidence that in the normal oxidation of tyrosine 



~° Alkaptonurics may give a positive Wassermann reaction without other evi- 

 dence of syphilis, and in one case this reaction disappeared when the patient 

 was given large amounts of tvrosine (Soderbergh, Nord. Med. Arkiv., 1915 (48), 

 1). 



^^ The older writers stated that uroleucic acid commonly accompanied homo- 

 gentisic acid in the urine of alkaptonuria, but later observations do not conhrm 

 this. (Oswald, Zeit. phvsiol. Chem., 1914 (93), 307). 



■- Jour. Biol. Chem., 1911 (9), 139 and 151. 



