The Bile Acids Chemistry, Physiology, and Metabolism: Volume 1: Chemistry

381 Pages·1971·16.8 MB·English

by  David Kritchevsky

Padmanabhan P. Nair · David Kritchevsky Editors
Chemistry
THE BILE ACIDS
Chemistry, Physiology, and Metabolism
VOLUME 1: CHEMISTRY
Contributors to This Volume
W. H. Elliott J. T. Matschiner
Department of Biochemistry Department of Biochemistry
Saint Louis University Sai11t Louis University
St. Louis, Missouri St. Louis, Missouri
P. Eneroth P. P. Nair
Department of Chemistry Biochemistry Research Division
Karolinska Institute Department of Medicine
Stockholm, Sweden Sinai Hospital of Baltimore
Baltimore, Maryland
S.L. Hsia
R. Ryhage
Departments of Biochemistry
Laboratory for Mass Spectrometry
and Dermatology Karolinska Institute
University of Miami School of Medicine Stockholm, Sweden
Miami, Florida
J. Sjovall
D. Kritchevsky
Department of Chemistry
The Wistar Institute Karolinska Institute
Philadelphia, Pennsylvania Stockholm, Sweden
A. Kuksis D. Small
Banting and Best Department Section of Biophysics
of Medical Research Department of Medicine
University of Toronto Boston University School of Medicine
Toronto, Canada Boston, 1\Jassachusetts
THE BILE ACIDS
Chemistry, Physiology, and Metabolism
VOLUME 1: CHEMISTRY.
Edited by
Padmanabhan P. Nair
Biochemistry Research Division
Department of Medicine
Sinai Hospital of Baltimore, Inc.
Baltimore, Maryland
and
David Kritchevsky
The Wistar Institute
Philadelphia, Pennsylvania
<:£>
SPRINGER SCIENCE+ BUSINESS MEDIA, LLC 1971
Library of Congress Catalog Card Number 71-138520
ISBN 978-1-4757-0649-9 ISBN 978-1-4757-0647-5 (eBook)
DOI 10.1007/978-1-4757-0647-5
© 1971 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1971
All rights reserved
No part of this publication may be reproduced in any form
without written permission from the publisher
Preface
The bile acids as principal end products of cholesterol metabolism
occupy a focal position in our understanding of the role of steroids in bio
logical systems. The biogenesis of bile acids from cholesterol in higher ani
mals, and their functions in regulating sterol metabolism and in gastrointestinal
physiology have been elucidated by the development of elegant methodo
logical approaches during the last two decades. The molecular pleomorphism
exhibited by the bile acids and bile alcohols in the animal kingdom is a classic
example of their role in biochemical evolution.
The total story of the bile acids, their chemistry, their role in normal
and abnormal physiological processes, and their significance in biochemical
evolution has never been available in the form of a comprehensive treatise
written in the words of those who have contributed to the development of
our knowledge in this area. The Bile Acids, in two volumes, will serve to
fill this void, and will also bring together information which will prove in
valuable to both the biochemist and the medical scientist.
We wish to thank Mrs. Sally Wiseman and Mrs. Lillian Haas for their
invaluable assistance with the editing of the manuscripts. This work was
supported in part by grants AM-02131, General Research Support SS0-1-
FR-05479 (P.P.N.), HE-03299, HE-05209, and a National Heart Institute
Research Career Award (D.K. ), K6-HE-734, from the National Institutes of
Health, United States Public Health Service.
P.P.N.
Baltimore, Maryland
D.K.
Philadelphia, Pennsylvania
v
Contents
Chapter 1
Chemistry of the Bile Acids
by David Kritchevsky and Padmanabhan P. Nair
I. Historical . . . . . . . .. . . .. .. . .. . . .. .. . . .. .. . . .. .. . . .. . .. .. .. .. .. . .. . .. . .. . .. . . . . . . . 1
II. Structure of the Bile Acids .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 3
III. Naturally Occurring Bile Acids .......................................... 6
A. Bile Acids with 24 Carbon Atoms .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 6
B. Bile Acids with 27 and 28 Carbon Atoms ........................ 7
C. Conjugates of Bile Acids ............................................. 8
D. The Bile Alcohols ...................................................... 9
IV. Chemical Reactions ......................................................... 9
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Chapter 2
Naturally Occurring Bile Acids and Alcohols and Their Origins
by Jol.n T. Matschiner
I. Introduction . .. . . .. .. . .. . . . . .. . .. . . .. .. . . .. .. . . .. .. . .. . .. .. . .. . . .. . .. . .. . .. . 11
II. Naturally Occurring Bile Salts .......................................... 12
A. Early Observations ................................................... 12
B. Isolation ................................................................ 13
C. Structural Identification ........................................... 14
D. Tabulation of Known Acids and Alcohols ................... 16
III. Summary ..................................................................... 40
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Chapter 3
Allo Bile Acids
by William H. Elliott
I. Introduction ................................................................ 47
II. Historical Background and Occurrence .. .. . .. .. .. .. .. .. .. .. .. .. .. .. . 48
III. Separation, Isolation, Chromatography............................... 56
A. Separation and Isolation . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 56
B. Chromatography . . . . . . . . .. . . . . . . .. . . . . . . . . . . . . . . .. .. . .. . . . . . . . . . . . . . 57
IV. Physical Properties ......................................................... 64
vii
viii Contents
A. Optical Activity ...................................................... 65
B. Infrared Spectrometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
C. Mass Spectrometry ................................................. 66
V. Chemical Properties and Determination ............................ 70
VI. Preparation of Allo-Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
A. General Methods as Applied to Allocholic Acid ............ 70
B. Other Allo-Acids .................................................... 75
C. Conjugated Acids .................................................... 78
VII. Biosynthesis of Allo Bile Acids ........................................ 78
A. From Cholestanol and Cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
B. From 5(3 Bile Acids ................................................. 82
C. From Other Sa sterols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
VIII. Metabolic Transformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
A. Allolithocholic Acid ................................................. 87
B. Allochenodeoxycholic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
C. Allodeoxycholic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
D. Allocholic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
E. 3(3,6(3-Dihydroxyallocholanoic Acid ............................ 88
F. 3(3-Acetoxychol-5-Enoic Acid ..................................... 88
IX. Summary ..................................................................... 88
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Chapter 4
Hyocholic Acid and Muricholic Acids
by S. L. Hsia
I. Introduction ................................................................ 95
II. Isolation of Hycholic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
III. Isolation of a-, (3-, and w-Muricholic Acids . . . . . . . . . . . . . . . . . . . . . . . . . 97
IV. Elucidation of Structures ................................................ 98
A. Structure of Hyocholic Acid ..................................... 98
B. Structures of the Muricholic Acids ............................ 102
V. Partial Syntheses ......................................................... 108
A. Preparation of Chenodeoxycholic Acid . . . . . . . . . . . . . . . . . . . . . 108
B. Preparation of 3a,6a-Dihydroxy-7-keto-5(3-Cholanic
Acid ............................................................. Ill
C. Preparation of Hyocholic Acid from 3a,6a-Dihydroxy-
7-Keto-5(3-Cholanic Acid .................................. 114
D. Preparation of w-Muricholic Acid ............................ 114
E. Preparation of a-Muricholic Acid .............................. 115
F. Preparation of (3-Muricholic Acid .............................. 116
VI. Taurochenodeoxycholate 6(3-Hydroxylase of Rat Liver ......... 116
References .. . .. . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 119
Contents ix
Chapter 5
Extraction, Purification, and Chromatographic Analysis of Bile
Acids in Biological Materials
by P. Eneroth and J. Sjovall
I. Introduction ............................................................... 121
II. Extraction .................................................................. 122
A. Extraction with Solvents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
B. Extraction with Solids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
III. Steps Following Extraction ........................................... 125
A. Purification and Separation Without Previous Hydrolysis
of Conjugated Bile Acids .................................. 125
B. Hydrolysis of Conjugated Bile Acids and Subsequent
Purification Steps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
IV. Chromatographic Identification and Quantitation ............... 138
A. Thin-Layer and Glass Fiber Paper Chromatography ...... 139
B. Derivative Formation ............................................. 148
C. Gas-Liquid Chromatography .................................... 150
V. Application of Chromatographic Methods to Specific
Analytical Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
A. Bile and Intestinal Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
B. Plasma and Urine ................................................... 164
C. Tissues.................................................................. 165
D. Feces .................................................................. 166
VI. Conclusion ................................................................ 167
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
Chapter 6
Ion-Exchange Chromatography of Bile Acids
by A. Kuksis
I. Introduction ............................................................... 173
II. Theoretical Considerations ............................................. 174
A. Some Physical Properties of Bile Acids and Their Amino
Acid Conjugates .............................................. 174
B. Some Chemical and Physical Characteristics of Synthetic
Anion Exchangers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
C. Binding of Bile Acids to Anion-Exchange Resins .......... 179
D. Principles of Ion-Exchange Chromatography ............... 182
III. Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
A. Utilization oflon-Exchange Resins ........................... 184
B. Electrochromatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
C. Detection of Bile Acids . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . 194
IV. Nature of Resolution .................................................... 196
X Contents
V. Applications ............................................................... 198
A. Isolation and Purification ........................................ 198
B. Separation ............................................................ 201
C. Ion-Exchange Resins as Therapeutic Bile Acid
Sequestrants ................................................... 203
VI. Summary and Conclusions ............................................. 205
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
Chapter 7
Mass Spectra of Bile Acids
by J. Sjovall, P. Eneroth, and R. Ryhage
I. Introduction ............................................................... 209
II. Conditions for Gas Chromatography-Mass Spectrometry ...... 210
III. General Fragmentation of Bile Acid Derivatives ................ 213
IV. Fragmentation Patterns of Nonketonic Bile Acid
Derivatives .................................................... 219
A. Monohydroxy Bile Acids ........................................ 219
B. Dihydroxy Bile Acids .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 224
C. Trihydroxy Bile Acids ............................................ : 232
V. Fragmentation Patterns of Ketonic Bile Acids ................... 237
A. 3-Keto Bile Acids ................................................... 237
B. 6-Keto Bile Acids .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 238
C. 7-Keto Bile Acids ................................................... 239
D. 12-Keto Bile Acids ................................................. 246
VI. Conclusion ................................................................ 246
References .................................................................. 247
Chapter 8
The Physical Chemistry of Cholanic Acids
by Donald M. Small
I. Introduction . .. . .. .. . .. . .. . .. . .. . .. .. .. .. . .. . .. . .. . . .. .. . .. . .. . .. . .. . . .. . . . 249
II. Molecular Structure ...................................................... 251
A. Chemical Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
B. Formulae and Molecular Models .............................. 251
C. Infrared Spectra (IRS) of Bile Acids ................ 255
1. .......
D. Nuclear Magnetic (NMR) Resonance Spectroscopy ....... 262
III. Physical Constants ...................................................... 265
A. Molecular Weight and Melting Point ......................... 265
B. Density and Apparent Specific Volume ...................... 267
C. Miscellaneous Physical Properties .............................. 268
IV. Crystalline Structure .................................................... 269
V. Surface Chemistry of Bile Acids and Bile Salts .................. 270
A. Insoluble (Stable) Monolayers of Bile Acids ................ 270