31 - Disorders of Bile Acid Synthesis and Metabolism: A Metabolic Basis for Liver Disease

Summary

With the increased recognition of the importance of bile acid synthesis and metabolism in both normal physiology and pathophysiology, there has been a renaissance in this field in recent years. For such small and relatively simple molecules, the bile acids have amazingly diverse properties and functions. To the lipidologist, bile acid biosynthesis represents one of the major pathways for regulating cholesterol homeostasis; on the other hand, the hepatologist sees these molecules as essential for providing the major driving force for the promotion and secretion of bile and therefore as key elements in the development and maintenance of an efficient enterohepatic circulation. The gastroenterologist recognizes that bile acids play an important role in the solubilization and absorption of fats and fat-soluble vitamins in the small bowel, whereas in the large bowel, pathologists have viewed these molecules as potentially harmful in that they are cathartic, membrane damaging, and promoters of colonic disease. With regard to bile acid biosynthesis, several comprehensive reviews of the subject have been published [1–4]; therefore, this chapter provides only an overview of the pathways of bile acid synthesis and metabolism and describes specific inborn errors in bile acid synthesis that have been identified.

PATHWAYS FOR BILE ACID SYNTHESIS FROM CHOLESTEROL

Although not generally thought of as steroids, the bile acids belong to this chemical class, possessing the basic cyclopentanoperhydrophenanthrene (ABCD ring) nucleus [5, 6]. They differ from steroid hormones and neutral sterols by having a five-carbon atom side chain with a terminal carboxylic acid (Figure 31.1).