An increased secretion of bile acids produces an increase in bile acid base physiology pdf. Approximately 600 mg of bile salts are synthesized daily to replace bile acids lost in the feces, although, as described below, much larger amounts are secreted, reabsorbed in the gut and recycled. Cholic acid is converted into deoxycholic acid and chenodeoxycholic acid into lithocholic acid.
The added solubility of conjugated bile salts aids in their function by preventing passive re-absorption in the small intestine. Critical micellar concentration” refers to both an intrinsic property of the bile acid itself and amount of bile acid necessary to function in the spontaneous and dynamic formation of micelles. Synthesis of bile acids is a major route of cholesterol metabolism in most species other than humans. Human adults secrete between 12-18 g of bile acids into the intestine each day, mostly after meals. 6 g, which means that bile acids are recycled several times each day.
Bile salts constitute a large family of molecules, composed of a steroid structure with four rings, a five- or eight-carbon side-chain terminating in a carboxylic acid, and several hydroxyl groups, the number and orientation of which is different among the specific bile salts. The four rings are labeled A, B, C, and D, from the farthest to the closest to the side chain with the carboxyl group. The D-ring is smaller by one carbon than the other three. The structure is commonly drawn with A at the left and D at the right.
All bile acids have a 3-hydroxyl group, derived from the parent molecule, cholesterol, in which the 3-hydroxyl is beta. There are multiple steps in bile acid synthesis requiring 14 enzymes in all. 3-hydroxyl is converted to the α orientation. The simplest 24-carbon bile acid has two hydroxyl groups at positions 3α and 7α. The term “cholan” denotes a particular steroid structure of 24 carbons, and the “24-oic acid” indicates that the carboxylic acid is found at position 24, at the end of the side-chain. Chenodeoxycholic acid is made by many species, and is the prototypic functional bile acid. Minor pathways initiated by 25-hydroxylase in the liver and 24-hydroxylase in the brain also may contribute to bile acid synthesis.
3α,7α,12α-trihydroxy-5β-cholan-24-oic acid, the most abundant bile acid in humans and many other species, was discovered before chenodeoxycholic acid. It is poorly water-soluble and rather toxic to cells. Different vertebrate families have evolved to use modifications of most positions on the steroid nucleus and side-chain of the bile acid structure. To avoid the problems associated with the production of lithocholic acid, most species add a third hydroxyl group to chenodeoxycholic acid.