334 



VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



other higher phenols, but also for benzoic acid, sex hormones, and many 

 other biologic products. The fact that phenol conjugates with glucuronic 

 acid was reported in 1883 by Kiilz,^"^ and was confirmed later.-"^ Neuberg 

 and Neimann^"^ and Salkowski and Neuberg-"^ were among the first to 

 describe this reaction. 



HCOH 



-CH 



+ 



HCOH 

 HCOH 

 HOCH I 

 HC 1 



O 



HCOH 



I 

 HCOH 



HOCH 



HC 



O + H2O 



COOH 



Glucuronic 

 acid 



COOH 



Phenyl glucuronide 



The Conjugation of Glucuronic Acid with Phenol, and the Resulting Formation of 



Phenylglucvironide 



When phenylglucuronide is injected, it is quantitatively excreted in the 

 urine by rabbits^*^ and by hens.^^* On the other hand, when this com- 

 pomid is given orally, it undergoes considerable hydrolysis, and some of it 

 is destroyed. Only approximately 50% of the dose can be accounted for 

 in the urine under these conditions. ^^^ A sharp rise in the ethereal sulfate 

 fraction of the urine occurs on the first day, and 15 to 20% of the dose of 

 glucuronide appears as the ethereal sulfate. ^^^ Moreover, Garton and 

 Williams ^^^ proved that the ethereal sulfate fraction under these condi- 

 tions contained quinol, catechol, and hydroxyquinol, in addition to phenol. 

 The several changes which take place are graphically represented in 

 Figure 5. 



The fact that no phenylsulfate appears in the urine after phenylglu- 

 curonide is injected, and that the phenylglucuronide is quantitatively re- 

 covered in the urine under these conditions, indicates that it does not 

 undergo hydrolysis when it is administered parenterally. Glucuronidase 

 apparently does not exert its hydrolytic function in the intact animal under 

 these conditions. ^^^ 



e'. Oxidation of Benzene to Muconic Acid: In 1909, Jaffe^^^ first iso- 

 lated muconic acid, HOOC-CH:CH-CH:CH-COOH, from the urine of 



205 E. Kiilz, Arch. ges. Physiol. (Pfluger's), SO, 484-485 (1883). 



206 E. Kiilz, Z. Biol, 27 {n.s. S], 247-258 (1890). 



20' C. Neuberg and W. Neimann, Z. physiol. Chem., U, 114-126 (1905). 

 208 E. Salkowski and C. Neuberg, Biochem. Z., 2, 307-311 (1907). 



