Conjugation and excretion of the amino and acetamido benzoic acids

Abstract

The conjugation of the aminobenzoic acids with glycine and glucuronic acid has been measured in the rabbit and the dog. In both species the total conjugation is greatest with the ortho isomer, least with the para. In the rabbit, the amount of hippurate formed is greater than the amount of glucuronide formed, and in each case, greatest with the ortho isomer and least with the para. These relations are determined by the comparative first-order reaction rates, the comparative zero-order reaction rates, the concentration of the aminobenzoic acid in the body at which the reaction changes from first-order to zero-order, and the dose. In the dog, the meta aminobenzoic acid forms more hippurate than glucuronide, as in the rabbit, but for the ortho and para isomers the formation of hippurate is much less than that of glucuronide. The meta and para acetamidobenzoates are conjugated to a smaller extent than are the aminobenzoates. Slices of kidney and liver perform these conjugations to an extent agreeing with that in the whole animal, in some but not all cases. It appears that both species form the three hippurates in the kidney, but in the liver by the rabbit only. Both species form the three glucuronides, probably in both kidney and liver.

Metabolism of <i>p</i>-Aminohippurate and its Relevance in Man

“…(4) Whereas all the above cited theories are based on the assumption that cortical PAH extraction is complete and PAH found in the renal vein comes from other sources than the cortex, it cannot be ruled out entirely that in complete PAH extraction may occur in the cortex as well [5,6,16,21], Our results indicate that the metabolism of PAH, notably the production of benzoates, is an eminently important factor which leads to an incomplete renal PAH secretion since benzoates undergo tubular reabsorption [1,7,20], Contrary to observations following a single high-dosage PAH injection (where the reabsorptive capacity has presumably been exceeded), we could never find benzoates in urine samples. However, benzoates make up 75% of all aromatic amines present in the renal vein.…”

Hippurate: The Natural History of a Mammalian–Microbial Cometabolite

“…Indeed, in the dog it would seem that the liver has no part in hippurate synthesis and that this occurs in the kidney. 66…”

“…These differences have been attributed to the dose of benzoic acid administered, and also interspecies variation in the glycine and the glucuronic acid conjugation capacity of kidney and liver cells, and the rate of glycine mobilization. , In man, hippurate synthesis occurs in both the liver and cortical cells of the kidney; ,, although, it is thought that, due to the anatomical position and larger mass of the liver, this organ is more quantitatively significant for the glycine conjugation of benzoic acid. , However, it is also important to note the major site of biosynthesis of hippurate is not always the liver. Indeed, in the dog it would seem that the liver has no part in hippurate synthesis and that this occurs in the kidney …”

Nephron Transport and Renal Tubular Effects of Cephaloridine in Animals

“…Chlorothiazide, PAH and p-amino-salicylic acid, compounds which are also secreted by the tubules (Weiner & Mudge, 1964), failed to protect mice even when administered in large doses. Orthoand para-aminobenzoic acids which are not actively excreted by the tubules (Knoefel, Huang & Despopoulos, 1959) were protective; benzoic acid which is not secreted by the tubules (Knoefel & Huang, 1956) was not protective.…”