The author wishes to apologize to the reader for not being able to include details of several unpublished studies which were presented at the Kroc Conference. This was necessary so as not to jeopardize publication of the various articles, involving several collaborators, in peer-reviewed journals. Only a brief summary of results of these studies will be presented.
The Role of Calcium in the Pathogenesis of Gallstones: Ca++ Electrode Studies of Model Bile Salt Solutions and Other Biologic Systems†
Article first published online: 24 JUL 2008
Copyright © 1984 American Association for the Study of Liver Diseases
Volume 4, Issue S2, pages 228S–243S, September/October 1984
How to Cite
Moore, E. W. (1984), The Role of Calcium in the Pathogenesis of Gallstones: Ca++ Electrode Studies of Model Bile Salt Solutions and Other Biologic Systems. Hepatology, 4: 228S–243S. doi: 10.1002/hep.1840040842
- Issue published online: 24 JUL 2008
- Article first published online: 24 JUL 2008
- National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases. Grant Numbers: Grants AM 18887, AM 27104, Am 32130
- National Institutes of Health
Calcium is present in all pigment gallstones as a salt of one or more of the anions in bile which are most readily precipitable by calcium: (i) carbonate; (ii) bilirubinate; (iii) phosphate, and (iv) “palmitate”. We term these “calcium-sensitive” anions. In addition, since cholesterol stones have been found to contain pigment stone centers, we postulate that calcium precipitation in bile is a critical event in the initiation of cholesterol gallstones, so that the latter should be considered a two-stage process: (i) precipitation of calcium salts to form a nidus, and (ii) precipitation of cholesterol from its supersaturated state on this nidus. Any measure which will reduce free [Ca++] in bile will reduce calcium lithogenicity; possible ways to reduce [Ca++] in bile are presented. One way is to increase Ca++ binding by normal biliary constituents; we have recently pointed out that bile salts are important buffers for Ca++ in bile by virtue of binding to both free and micellar bile salts. Here, we consider some of our Ca++ electrode studies of taurocholate, glycocholate, serum albumin, and simple molecules having terminal carboxyl (COO−) or sulfonic (SO−3) ions. A brief history of the development of the Ca++ electrode is given, along with theoretical considerations of ionic activities and techniques of electrode measurements. From the various studies, a unifying hypothesis is proposed for the structural requirements of Ca++−binding to proteins (albumin) and free monomeric bile salts. For proteins, unconjugated bile salts and glycine-conjugated bile salts, it is proposed that Ca++ binding involves a reversible ion-exchange “site” in which a Ca++ ion is interposed between carboxyl (CO0− ) and hydroxyl (OH) groups. For taurine-conjugated bile salts, this “site” is proposed to involve the interposition of a Ca++ ion between the side-chain SO−3 and cholanic ring OH groups. These studies are a first step toward modulation of Ca++ activity in bile.