Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol

Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol In the liver, synthesis of bile acids and bile salts is initiated with the conversion of cholesterol to 7alpha-hydroxycholesterol and of 7alpha-hydroxycholesterol to 4-cholesten-7alpha-ol-3-one. The pathway then branches: hydroxylation of 4-cholesten-7alpha-ol-3-one to 4-cholesten-7alpha, 12alpha-diol-3-one leads ultimately to the formation of cholate, while its reduction to 5beta-cholestan-7alpha-ol-3-one leads to chenodeoxycholate formation. The amounts of substrate following each branch appear to be determined by abundance of the hydroxylase enzyme: in human liver, cholate synthesis predominates.In both branches, reactions in the cytosol, the mitochondrial matrix, and the peroxisomal matrix result in modifications to the ring structure, shortening and oxidation of the side chain, conversion to a Coenzyme A derivative, and conjugation with the amino acids glycine or taurine. In the body, glycocholate, taurocholate, glycochenodeoxycholate, and taurochenodeoxycholate are released from hepatocytes into the bile and ultimately into the lumen of the small intestine, where they function as detergents to solubilize dietary fats. The liver synthetic pathway also yields small amounts of bile acids, cholate and deoxycholate, which may play a feedback role in regulating the bile acid synthetic pathway (Russell 2003). These reactions are outlined in the figure below.