Glycocholic

Glycocholic acid is a conjugated bile acid found in the bile of many mammals, including humans. It is formed when the primary bile acid cholic acid undergoes conjugation with glycine in the liver, producing a more water‑soluble derivative that is secreted into the bile canaliculi. The result is a 24‑carbon steroid nucleus with a hydrophilic side chain bearing a glycine residue.

The chemical structure of glycocholic acid consists of the familiar D‑A/B ring system of steroids, with hydroxyl groups at positions 3, 7, 12 and 17. The C‑27 carboxylate is linked to glycine via an amide bond, giving the molecule a net negative charge at physiological pH. This amphipathic nature enables glycocholic acid to act as an anionic detergent in the intestinal lumen.

Biosynthesis of glycocholic acid follows the classic cholesterol‑to‑bile‑acid pathway. Cholesterol is converted to 7α‑hydroxy‑cholesterol, then to cholic acid through multiple oxidation and reduction steps. In hepatocytes, cholic acid is conjugated by the enzyme bile‑acid‑CoA:amino‑N‑acyltransferase (BAAT) with glycine. The conjugation increases solubility and reduces the tendency of bile acids to precipitate in the acidic environment of the stomach.

In the small intestine, glycocholic acid emulsifies dietary fats, increasing the surface area for pancreatic lipase activity. It also facilitates the formation of mixed micelles that transport lipophilic nutrients across the epithelial cell membrane. After absorption, glycocholic acid is taken up by the portal circulation and returned to the liver in a process known as enterohepatic circulation.

Clinically, glycocholic acid is used in research studies to investigate bile acid transport mechanisms and in the development of bile‑acid‑targeted drug delivery systems. Diagnostic tests measuring levels of glycocholic and other bile acids in serum or urine can help detect cholestatic liver diseases and assess the efficiency of bilirubin excretion. Recent studies suggest that altered glycocholic acid profiles may be associated with gastrointestinal disorders such as irritable bowel syndrome and colorectal cancer.