Hofmann Alan F
Division of Gastroenterology, Department of Medicine, University of California, San Diego, San Diego, CA 92093-0063, USA.
Hepatology. 2009 May;49(5):1403-18. doi: 10.1002/hep.22789.
An informal review of the author's five decades of research on the chemistry and biology of bile acids in health and disease is presented. The review begins with a discussion of bile acid structure and its remarkable diversity in vertebrates. Methods for tagging bile acids with tritium for metabolic or transport studies are summarized. Bile acids solubilize polar lipids in mixed micelles; progress in elucidating the structure of the mixed micelle is discussed. Extensive studies on bile acid metabolism in humans have permitted the development of physiological pharmacokinetic models that can be used to simulate bile acid metabolism. Consequences of defective bile acid biosynthesis and transport have been clarified, and therapy has been developed. Methods for measuring bile acids have been improved. The rise and fall of medical and contact dissolution of cholesterol gallstones is chronicled. Finally, principles of therapy with bile acid agonists and antagonists are given. Advances in understanding bile acid biology and chemistry have helped to improve the lives of patients with hepatobiliary or digestive disease.
本文对作者五十年来在健康与疾病状态下胆汁酸化学与生物学方面的研究进行了非正式回顾。回顾首先讨论了胆汁酸的结构及其在脊椎动物中的显著多样性。总结了用氚标记胆汁酸用于代谢或转运研究的方法。胆汁酸可在混合微团中溶解极性脂质,文中讨论了阐明混合微团结构方面的进展。对人体胆汁酸代谢的广泛研究使得能够开发出生理药代动力学模型,用于模拟胆汁酸代谢。已明确胆汁酸生物合成和转运缺陷的后果,并开发了相应治疗方法。测量胆汁酸的方法也得到了改进。记录了胆固醇胆结石医学溶解和接触溶解的兴衰历程。最后给出了胆汁酸激动剂和拮抗剂的治疗原则。对胆汁酸生物学和化学认识的进展有助于改善肝胆或消化系统疾病患者的生活。