The Conjugation of Benzoic Acid in Man*

The extensive investigations on the conjugation of benzoic acid, since Wohler’s discovery in 1824 of the synthesis of hippuric acid by the animal, have failed to furnish a comprehensive and definite concept of the metabolic and chemical changes taking place when benzoic acid is introduced into the organism. No attempt has ever been made to explain why man eliminates benzoic acid almost completely as hippuric acid while the dog excretes it mainly as glycuronic acid monobenzoate. Indeed many investigators have entirely ignored the fact that benzoic acid can be and is combined with glycuronic acid, and have recorded their determinations of total combined benzoic acid as hippuric acid. The seriousness of this error can be readily appreciated when one recalls that in the dog, glycuronic acid monobenzoate constitutes roughly three-quarters of the total combined benzoic acid, and that even in man varying amounts of benzoic acid combined with glycuronic acid may be excreted. The lack of a specific and reliable quantitative method until recently for the determination of hippuric acid has been another serious source of error. The conjugation of benzoic acid constitut,es a problem which deserves careful study because it offers a promising approach to the investigation of intermediary metabolism. The well known theory of P-oxidation of fatty acids was developed from the study of the fate of benzoic acid and its homologs in the body. It is highly probable that further work on the behavior of aromatic compounds, such as benzoic acid, which can elicit a physiological