The Site of the Synthesis of Hippuric Acid and Phenylaceturic Acid in the Dog*

At present the view is commonly accepted that hippuric acid is produced chiefly by the kidney in most animals and exclusively by that organ in the dog. This conclusion is based largely on the well known work of Bunge and Schmiedeberg (1) who were able to dem0nstrat.e that hippuric acid was formed when blood containing benzoic acid and glycine was perfused through dog kidney. Furthermore, they failed to find hippuric acid after injecting sodium benzoate and glycine into dogs in which the renal blood vessels were tied, but could find it when the ureters were ligated and the vascular supply of the kidneys left intact. Although these findings appear to constitute almost conclusive proof that in the dog, the synthesis of hippuric acid is effected only by the kidney, Kingsbury and Bell (2) challenged these conclusions. They reported that after injecting sodium benzoate and glycine into a nephrectomized dog, they were able to find hippuric acid in the blood and other tissues. Unfortunately, they did not differentiate between combined benzoic acid and hippuric acid, which is a serious error inasmuch as in the dog the conjugation with glycuronic acid is the more prominent. In only one experiment did they record the actual isolation of hippuric acid without, however, giving any information as to the amount. Snapper, Griinbaum, and Neuberg (3) criticized their conclusions and proceeded to reinvestigate the problem. They corroborated the work of Bunge and