- Understand the physiologic functions of bile as a route for excretion and in aiding in the digestion and absorption of dietary lipids
- Understand how bile acids are formed from cholesterol, how they are modified during gut passage, and their role in driving bile secretion
- Describe the mechanisms that regulate the rate of conversion of cholesterol into bile acids
- Describe the major biliary lipids and how they are transported into the canaliculus
- Describe how the composition of bile is modified as the bile moves through the biliary ductules
- Define the cellular transport mechanisms that render bile alkaline
- Understand the consequences of a failure to secrete bile, and conditions that cause this problem
The liver fulfills its excretory function by producing bile, a lipid-rich solution designed to promote the elimination of hydrophobic solutes. Bile consists of a micellar solution in which bile acids, products of hepatocytes produced by the metabolism of cholesterol, form mixed micelles with phosphatidylcholine. These mixed micelles solubilize molecules that would otherwise have minimal aqueous solubility, such as cholesterol itself and a variety of xenobiotics. In addition to its role in providing for excretion of hydrophobic waste products, bile also plays an important role in the digestion and absorption of lipids ingested in the diet. Bile acids form mixed micelles with the products of lipid digestion, increasing the rate at which they can diffuse across the aqueous environment of the gastrointestinal lumen. While bile acids are not essential for the uptake of most fatty acids, which have appreciable aqueous solubility, they do markedly increase the efficiency of this process. On the other hand, insoluble dietary lipids, such as saturated long-chain fatty acids and fat-soluble vitamins, are almost entirely dependent on micellar solubilization for absorption. In patients suffering from cholestasis, deficiencies of fat soluble vitamins can occur. Bile acids also influence bacterial populations in the gut, both by being (in micellar form) directly antimicrobial, and by inducing the expression of genes that protect against bacterial overgrowth.
Bile secretion in the liver is driven primarily by the active, ATP-dependent efflux of conjugated bile acids out of the hepatocyte into the canaliculus. In some animals, there is also a variable component of bile acid-independent bile flow, although the solutes that drive this secretion are not fully understood. But in humans, canalicular bile flow is almost entirely dependent on the secretion of bile acids. Thus, in this section, we will consider how bile acids are synthesized, and subsequent modifications to their structure that promote their role as biological detergents.
Formation of Bile Acids from Cholesterol
Bile acids are amphipathic end products of cholesterol metabolism. The term amphipathic refers to the fact that bile acids have both a hydrophobic and hydrophilic face, and form micelles. This is essential to their physiologic function, as will be discussed later.
Synthesis of bile acids from cholesterol occurs in the ...