4-Hydroxyhippuric, also known as 4-hydroxybenzoylglycine or 4-hydroxyhippate acid, is a metabolite of hippuric acid, and a uremic toxin. Benzoic acid is present in many fruits, such as apricots, prunes, and berries; many vegetables such as mushrooms (fungus), snap peas, cucumbers, and radishes; spices such as cinnamon, cloves, and allspice; nuts such as​ cashews, almonds, pistachios; and dairy products such as yogurt, milk, and cheese. Benzoic acid can also be synthesized by gut microbes through phenylalanine, however the exact mechanisms of synthesis in microbes is not well studied. Benzoic acid is transported out of the intestine via a monocarboxylate transporter into the blood. Then it is transported into the liver via another monocarboxylate transporter. In the mitochondira of the liver benzoic acid is catalyzed by the enzyme acyl-coenzyme A synthetase ACSM2A, mitochondrial, with ATP and coenzyme A into the metabolite Benzoyl-CoA. Benzoyl-CoA is then catalyzed by the enzyme glycine N-acyltransferase and a glycine, which produces hippuric acid. Hippuric acid leaves the mitochondria and is metabolized in the membrane of the endoplasmic reticulum by the enzyme cytochrome P450 1A2 to produce 4-Hydroxyhippuric. 4-Hydroxyhippuric is transported into the blood by a monocarboxylate transporter. 4-Hydroxyhippuric inhibits the Ca2+-ATPase on the plasma membrane of erythrocytes. This leads to apoptosis of the erythrocytes. It also induces free radical production in the renal proximal tubular cell line.

Metabolism and Physiological Effects of 4-Hydroxyhippuric Acid References