Metabolic conjugations of p-aminobenzoic acid in the rat.

The acetylation of p-aminobenzoic acid (PAB) (2) and of sulfanilamide (3) by the rat has been shown to depend upon an adequate supply of pantothenic acid, a constituent of the coenzyme A molecule (4). In addition the extent of acetylation is decreased by giving large amounts of PAB with reference to the size of the animal (5, 6) and to a smaller extent by a deficiency of riboflavin (5). The present communication emphasizes an additional complexity in this acetylation. Whereas acetyl conjugation represents the major metabolic change of sulfonamides (7), aromatic amines containing a carboxyl group may also be conjugated with glycine to form the corresponding hippuric acid derivatives, a reaction which has had considerable study recently in the case of PAB (8-11). This reaction yields p-aminohippuric acid (PAH) from PAB, or acetylPAH if conjugation occurs at both functional groups. In the present investigation we have found that PAH is acetylated by the rat at a rate different from PAB. Therefore the total amount of PAB acetylated depended on the rate at which it was conjugated with glycine before it was acetylated. Any factors which modified the extent of glycine conjugation also modified the extent of acetylation. All such factors must be considered when PAB is used as a test substance for assaying pantothenate deficiency in animals. Conversely, factors which modified the extent of acetylation were found to modify glycine conjugation. The resultant of these interrelationships was that a nearly constant proportion of administered PAB was conjugated in at least one position under a number of divergent conditions.