BILE ACIDS

Bile acids facilitate digestion and absorption of lipids in the small intestine



Bile acids facilitate digestion and absorption of lipids in the small intestine

Thesis statement

How do bile acids facilitate digestion and absorption of lipids in the small intestine?

Introduction

In vertebrates, cholesterol balance is achieved by modulating both synthesis and excretion. Cholesterol excretion is mediated by bile acids, the water-soluble amphipathic molecules formed from cholesterol in the hepatocyte. In addition to their role in cholesterol homeostasis, bile acids also are functional detergents that induce bile flow and transport lipids as mixed micelles in the biliary tract and small intestine.

Bile, a fluid secreted by the liver into the intestine in vertebrates, is both a digestive and an excretory fluid. As a digestive fluid, bile contains bile acids, potent digestive surfactants that promote lipid absorption. As an excretory fluid, bile contains substances that cannot be eliminated efficiently in urine because they are insoluble or protein bound. These include not only bile acids (which are not only digestive surfactants but also end products of cholesterol metabolism), bilirubin (the end product of heme metabolism), cholesterol (derived from synthesis exceeding body needs), and heavy metals such as iron and copper (derived from absorption exceeding body needs). Biliary secretion also provides an excretory route for lipophilic steroids and drug metabolites. Bile also has a high concentration of phospholipids, which consist mostly of phosphatidylcholine (PC) and which form mixed micelles with bile acids. These mixed micelles contain amphipathic microdomains that can solubilize cholesterol. Mixed micelle formation also lowers the monomeric activity of bile acids and prevents their destroying the apical membrane of the biliary epithelial cells. IgA, an immunoglobulin, and mucus are secreted into bile, where their role is to prevent bacterial growth and adhesion. Finally, bile contains tocopherol, which may prevent oxidative damage to the biliary and small intestinal epithelium (5).

Discussion

Bile acids are formed in the pericentral hepatocytes from cholesterol by a multienzyme process. In the biosynthesis of C24 bile acids (which are present in most vertebrates), the side chain of cholesterol undergoes oxidative cleavage resulting in the conversion of an isooctane moiety into an isopentanoic acid moiety. One or two hydroxyl groups are added to the nucleus. Although the pattern of hydroxylation varies between species, the hydroxylation is always on one face of the molecule, and the final product invariably has a hydrophobic face and a hydrophilic face, resulting in an amphipathic molecule. [Not all vertebrates form C24 bile acids. In ancient mammals such as the elephant and manatee, as well as in cartilaginous fish, C27 bile alcohols are formed. In reptiles, C27 bile acids are formed (9). The topology of a typical C24 bile acid is shown in Fig. 1 ]

FIGURE 1 . Space-filling model of a conjugated bile acid molecule showing its biplanar, amphipathic nature because of a hydrophobic face and a hydrophilic face. The large size of the molecule and the charged end group make the bile acid anion impermeable to cell membranes and paracellular ...