The Bile Acids: Chemistry, Physiology, and Metabolism: Volume 3: Pathophysiology

237 Pages·1976·4.32 MB·English

by  Harold J. Nicholas (auth.)

THE BILE ACIDS
Chemistry, Physiology, and Metabolism
VOLUME 3: PATHOPHYSIOLOGY
THE BILE ACIDS
Volume 1: Chemistry
Volume 2: Physiology and Metabolism
Volume 3: Pathophysiology
A Continuation Order Plan is available for tbis series. A continuation order will bring
delivery of each new volume immediately upon publication. Volumes are billed only upon
actual shipment. For further information please contact the publisher.
THE BILE ACIDS
Chemistry, Physiology, and Metabolism
VOLUME 3: PATHOPHYSIOLOGY
Edited by
Padmanabhan P. Nair
Sinai Hospital of Baltimore, Inc.
Baltimore, Maryland
and
David Kritchevsky
The Wistar Institute
Philadelphia, Pennsylvania
PLENUM PRESS. NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Many entry under tide:
The Bile acids.
Includes bibliographical references.
CONTENTS: v.I. Chemistry.-v. 2. Physiology and Metabolism.-v. 3. Patho
physiology.
1. Bile acids. 2. Bile salts. I. Nair, Padmanabhan, P., 1931- ed. n. Krit-
chevsky, David, 1920- ed.
QP752.B54B54 599'.01'9243 71-138520
ISBN 978-1-4615-7565-8 ISBN 978-1-4615-7563-4 (eBook)
DOI 10.1007/978-1-4615-7563-4
© 1976 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1976
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
All rights reserved
No part of this book may be reproduced. stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
CONTRIBUTORS
George Bonorris JayW. Marks
Section of Gastroenterology Section of Gastroenterology
Department of Medicine Department of Medicine
Cedars-Sinai Medical Center Cedars-Sinai Medical Center
Los A ngeles, California Los Angeles, California
Robert L. Campbell
Department of Surgery E. H. Mosbach
Wayne State University School of Medicine
Department of Lipid Research
Detroit, Michigan
The Public Health Research Institute
of the City of New York, Inc.
Jacqueline Dupont New York City, New York
Department of Food Science and Nutrition
Colorado State University
Fort Collins, Colorado P. P. Nair
Biochemistry Research Division
Helmut Greim Department of Medicine
Sinai Hospital of Baltimore, Inc.
Abteilung fUr Toxikologie
Baltimore, Maryland
Gesellschaft fUr
Strahlen-und-Umweltforschung
Neuherberg, Germany
Harold J. Nicholas
M. J. Hill Institute of Medical Education and Research
and Department of Biochemistry
BacterialMetabolism Research Laboratory St. Louis University School of Medicine
Rear of Colindale Hospital St. Louis, Missouri
London, England
Phyllis Janson Norman D. Nigro
Department of Food Science and Nutrition Department of Surgery
Colorado State University
Wayne State University School of Medicine
Fort Collins, Colorado
Detroit, Michigan
David Kritchevsky Suk Yon Oh
The Wistar Institute of Anatomy Department of Food Science and Nutrition
and Biology Colorado State University
Philadelphia, Pennsylvania Fort Collins, Colorado
v
vi
Contributors
G. Saten Leslie J. Schoenf ield
College of Medicine and Dentistry Section of Gastroenterology
of New Jersey Department of Medicine
New Jersey Medical School Cedars-Sinai Medical Center
Newark, New Jersey and Los Angeles, California
East Orange Veterans Administration
Hospital Jon A. Story
East Orange, New Jersey The Wistar Institute of Anatomy and Biology
Philadelphia, Pennsylvania
PREFACE
The first two volumes of this series addressed themselves to the
chemistry, physiology, and metabolism of the bile acids. The present
volume is devoted to the pathophysiology of bile acids.
As the role of bile acids in health and disease is being increasingly
recognized, we have chosen for discussion a wide range of topics of current
importance. The presence of bile acids in brain tissue and their possible role
in demyelinating diseases form the subject of a provocative discussion. As
an extension of this theme, the presence and quantification of bile acids in
extrahepatic tissues is the subject of one chapter. The pathophysiological
implications of bile acids at the macromolecular level is highlighted by a
chapter on the influence of bile salts on the activity of various enzymes.
The general area of hepatobiliary diseases is discussed in two chapters:
one describes changes in bile salt metabolism in liver diseases and the other
focuses on cholesterol gallstones and their formation and dissolution.
Cerebrotendinous xanthomatosis has been shown to entail a defect in
bile acid and sterol metabolism, and this metabolic error is the subject of an
illuminating exposition.
There is presently a concerted research effort being brought to bear on
the causes of colon cancer, and one important aspect of this work centers
on bile acid metabolism. Aspects of bile acid metabolism and cancer are the
subject of two chapters. And finally, the role of dietary fiber in bile acid
metabolism is updated.
We wish to acknowledge the invaluable assistance of Miss Jane T.
Kolimaga in the preparation of the indexes. This work was supported in
part by Grants HL-03299, HL-05209, AM-02l31 and a Research Career
Award (DK), HL-0734 from the National Institutes of Health, United
States Public Health Service.
P.P. N.
Baltimore, Maryland
D.K.
Philadelphia, Pennsylvania
vii
CONTENTS
Chapter 1
Bile Acids and Brain ...... . . . . . . . . . . • . . . . . . • . • • • . . . . . . . • . . . . . . . . 1
by Harold J. Nicholas
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1
II. Brain Cholesterol Biosynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 2
III. Brain Cholesterol Turnover ................................ 3
IV. Reactions of Normal Brain Tissue with the Cholesterol Nucleus .. 5
V. Reactions of Brain with the Side Chain of Cholesterol . . . . . . . . .. 8
VI. Brain, Bile Acids, and the Demyelinating Diseases ............. to
References .............................................. 12
Chapter 2
Tissue Distribution of Bile Acids: Methodology and Quantification 17
by Jacqueline Dupont, Suk Yon Oh, and Phyllis Janson
I. Introduction .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 17
II. Extraction Methodology ................................... 18
III. Tests of Extraction Methods ............................... 19
A. Liquid-Liquid ........................................ 19
B. Liquid-Solid.......................................... 20
IV. Quantification and Identification Methodology. . . . . . . . . . . . . . .. 23
V. Tissue Cholanoic Acids: Results of Quantitation ............... 23
References .............................................. 27
Chapter 3
Bile-Salt-Protein Interactions ...•....•.....•....•.....••......... 29
by P. P. Nair
I. Introduction ............................................. 29
II. Nature of Molecular Interactions ........................... 30
ix
x Contents
III. Covalent Linkage of Bile Acids to Proteins ................... 31
IV. Molecular Interactions and Enzymatic Activity ............... 34
A. Sterol Ester Hydrolases ................................ 34
B. Lipases .............................................. 37
C. Esterases ............................................. 40
D. Arylsulfatases ........................................ 42
E. fI-Galactosidases and Amylase .......................... 42
F. Nucleotidases and Phosphatases ......................... 44
G. Peptide Bond Hydrolases ............................... 46
H. Oxidoreductases ...................................... 48
I. Other Bile-Salt-Protein Interactions ...................... 48
V. Pathophysiological Implications ............................ 49
References .............................................. 49
Chapter 4
Bile Acids in Hepato-Biliary Diseases. . . . . . . • • • . • . • . . . . • • • . . . . . . . .. 53
by Helmut Greim
I. Introduction ...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 53
II. Bile Acid Metabolism in Hepatic Diseases .................... 53
A. Changes in the Steroid Nucleus .......................... 55
B. Changes in the Ratio of Glycine and Taurine Conjugates .... 56
C. Sulfation and Glucuronidation ........................... 58
D. Differences in Bile Acid Metabolism Between Laboratory
Animals and Man . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 59
III. Role of Bile Acids in Hepato-Biliary Disorders ................ 59
A. Hepatocellular Necrosis ................................ 60
B. Inhibition of Drug Metabolism .......................... 61
C. Pruritus.............................................. 62
D. Malabsorption ........................................ 63
E. The Blind Loop Syndrome after Jejuno-Ileal Bypass ........ 64
F. Gallstone Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 65
IV. Bile Acid Kinetics, Pattern, and Concentration in Hepatic
Disorders .............................................. 67
A. Bile Acids for Diagnosis of Hepatic Disorders. . . . . . . . . . . . .. 69
B. Acute Hepatitis ....................................... 70
C. Chronic Hepatitis and Cirrhosis ......................... 71
D. Intra- and Extrahepatic Cholestasis ...................... 72
References .............................................. 74
Contents xi
Chapter 5
Pathophysiology and Dissolution of Cholesterol Gallstones •........... 81
by Jay W. Marks, George G. Bonorris, and Leslie J. Schoenfield
I. Biliary Lipid Physiology ................................... 82
A. Cholesterol ........................................... 82
B. Bile Acids ............................................ 84
C. Phospholipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 86
D. Bile Acid Regulation of Cholesterol and Phospholipid
Metabolism ........................................ 87
E. Biliary Secretion ...................................... 88
II. Pathophysiology of Cholesterol Gallstone Formation ........... 90
A. Stages of Gallstone Formation .......................... 90
B. Mechanism of Cholesterol Saturation ..................... 95
C. Role of the Gallbladder ................................. 99
D. Predisposing Factors ................................... 100
III. Chenodeoxycholic Acid Treatment of Gallstones .............. 103
A. Clinical Trials ........................................ 103
B. Mechanism of Action .................................. 104
C. Dose ................................................ 105
D. Prophylaxis and Retained Stones ........................ 106
E. Side Effects .......................................... 106
IV. Potential Agents for Treatment of Cholesterol Gallstones ....... 108
References .............................................. 109
Chapter 6
The Metabolism of Sterols and Bile Acids in Cerebrotendinous
Xanthomatosis ••............................•....•..... 115
by G. Salen and E. H. Mosbach
I. Introduction ............................................. 115
II. Clinical Manifestations .................................... 117
III. Biochemical Findings ..................................... 119
IV .. Inheritance ................................. " ........... 119
V. Tissue Concentrations of Cholesterol and Cholestanol in CTX ... 121
A. Brain Tissue .......................................... 121
B. Sterol Composition in Xanthomas ....................... 121
C. Sterol Composition in Tissues Other Than Brain ........... 122
D. Neutral Sterol Composition in Bile ....................... 124
E. Bile Acid Composition in Bile ........................... 125
VI. Quantitative Aspects of Cholesterol Turnover ................. 126