Studies in para-aminohippuric acid synthesis in the human: its application as a liver function test.

Synthesis of p-aminohippuric acid (PAH) from p-aminobenzoic acid (PAB) in animal liver slices and homogenates has been shown to resemble closely, both chemically and thermodynamically, the synthesis of peptides (1-3). This reaction has been utilized in the hippuric acid synthesis test for liver function since 1933 (4) and has found wide clinical application (5-7). Hippuric acid, however, must be determined in the urine and, consequently, relatively normal renal excretion is necessary. The actual determination is tedious since it involves precipitation, drying, and weighing of the excreted hippuric acid and analysis by titration, and is subject to considerable technical error. Study of the metabolism of PAB has been somewhat complicated by the difficulty in separating it from the conjugated form, PAH, in body fluids. Using ethylene dichloride extraction of PAB, it has been shown that excretion of free PAB, PAH, and the acetylated forms follows the oral administration of PAB in the human (8). Ether extraction of PAB and quantitative determination of the fractions by the usual diazo reaction for sulfonamides were used in the studies of PAH synthesis in tissue homogenates (1, 2). Using modifications of the latter method for serum and urine, the present study was conducted to investigate further the synthesis of PAH in the human and the possibility of utilizing this synthesis as a liver function test.