Conjugation of Benzoic Acid with Glycine in the Human Fetal and Adult Liver and Kidney

Abstract

The rate of hippuric acid formation was measured in the homogenates obtained from 26 specimens of human adult liver, 9 specimens of human mid-gestational fetal liver, 5 specimens of human adult kidney and 11 specimens of human mid-gestational fetal kidney. The average (pmol/min/mg tissue +/- SD) rate of hippuric acid formation was 322 +/- 99 (adult liver), 7.6 +/- 3.6 (fetal liver), 284 +/- 117 (adult kidney) and 6.4 +/- 6.7 (fetal kidney). One third of the fetal livers and kidneys studied were inactive in the formation of hippuric acid. These findings indicate that the conjugation of carboxylic acid with glycine is poorly developed in the mid-gestational human fetus. The kinetics of the formation of hippuric acid were studied in 3 fetal and adult livers and also in 3 fetal kidneys and in 3 specimens of the cortex and medulla of adult kidneys. The transformation of the data into Eadie-Hofstee plots generated straight lines in fetal and adult livers and kidneys. The Michaelis-Menten constant for the formation of hippuric acid (mean +/- SD, mM) was 43.4 +/- 6.6 (adult liver), 27.3 +/- 10.1 (fetal liver), 33.3 +/- 6.1 (adult renal cortex), 34.7 +/- 11.3 (adult renal medulla) and 15.3 +/- 3.5 (fetal kidney). The maximum velocity of the reaction (mean +/- SD, pmol/min/mg tissue) was 204 +/- 47.8 (adult liver), 6.0 +/- 1.3 (fetal liver), 199 +/- 40.7 (adult renal cortex), 24.2 +/- 16.9 (adult renal medulla) and 6.4 +/- 1.8 (fetal kidney). The inhibitory effect of 8 drugs containing a carboxylic acid group on the rate of hippuric acid formation was studied in 3 adult livers. Salicylic acid and diflunisal were the most powerful as inhibitors. Ibuprofen, furosemide and sodium valproate were weak inhibitors, whereas ketoprofen, naproxen and captopril did not inhibit the formation of hippuric acid. The IC50 values (mean +/- SD) of salicylic acid and diflunisal on the rate of hippuric acid formation were 0.19 +/- 0.05 and 1.18 +/- 0.19 mM, respectively.