Table Of ContentBiochemistry
of Dioxygen
BIOCHEMISTRY OF THE ELEMENTS
Series Editor: Earl Frieden
Florida State University
Tallahassee, Florida
Volume 1 BIOCHEMISTRY OF NONHEME IRON
Anatoly Bezkorovainy
Volume 2 BIOCHEMISTRY OF SELENIUM
Raymond J. Shamberger
Volume 3 BIOCHEMISTRY OF THE ESSENTIAL
UL TRAT RACE ELEMENTS
Edited by Earl Frieden
Volume 4 BIOCHEMISTRY OF DIOXYGEN
Lloyd L. Ingraham and Damon L. Meyer
Volume 5 PHYSICAL METHODS FOR
INORGANIC BIOCHEMISTRY
John R. Wright, Wayne A. Hendrickson,
Shigemasa Osaki, and Gordon T. James
A Continuation Order Plan is available for this 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.
Biochemistry
of Dioxygen
Lloyd L. Ingraham
and
Damon L. Meyer
University of California, Davis
Davis, California
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Ingraham, Lloyd, L.
Biochemistry of dioxygen.
(Biochemistry of the elements; v. 4)
Includes bibliographies and index.
1. Oxygen-Metabolism. I. Meyer, Damon, L.II. Title. III. Series.
QP535.01146 1985 599'.019214 85-12055
ISBN-13: 978-1-4612-9501-3 e-ISBN-13: 978-1-4613-2475-1
DOl: 10.1007/978-1-4613-2475-1
©1985 Plenum Press, New York
Softcover reprint of the hardcover 1s t edition 1985
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
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
Preface
This book is written for the research biochemist who needs to know more about
the particular field of dioxygen metabolism, whether this be for designing lectures
for a graduate level course or for his or her own research needs. We hope
researchers in a given area of dioxygen metabolism will gain knowledge of
related fields of dioxygen metabolism.
We have decided to use the term dioxygen to distinguish molecular oxygen
from divalent oxygen in water and organic compounds, dioxygen being a simpler
term than molecular oxygen. We do not intend to review the metabolism of all
compounds that contain oxygen, since this would include all of biochemistry.
An understanding of dioxygen chemistry is essential to the discussion of
the biochemistry of dioxygen. While this statement could be made about any
biochemical constituent, the chemistry of dioxygen is so unusual that interpre
tations without detailed chemical background are futile. Prediction of dioxygen
reaction products by analogy with other oxidants is impossible.
The partial reduction products of dioxygen, superoxide ion and peroxides,
develop naturally in the chemistry of dioxygen. It would be difficult to discuss
dioxygen biochemistry without first discussing these partial reduction products.
The first chapters stress the chemistry of dioxygen. These are followed by
chapters that delve into the intricacies of dioxygen metabolism. This procedure
has tended to divide the book into two sections. The sections are purposely not
well defined because certain biological reactions of dioxygen and the reduction
products of dioxygen are better discussed in the early chemical chapter.
After an introductory chapter, the discussion is focused on the chemistry
and physical properties of ground-state triplet dioxygen. An important aspect of
dioxygen chemistry is the kinetic barrier to oxidations by dioxygen. Because of
this kinetic barrier, there is a need for a mechanism to activate dioxygen before
it can oxidize most substrates.
The activation of dioxygen in biological systems is usually accomplished
by a metalloenzyme. These form metal-dioxygen complexes that are commonly
diamagnetic. These (singlet-state) metal-dioxygen complexes perform the great
majority of the biological oxidations. Singlet metal dioxygen complexes react
v
vi Preface
much more like singlet dioxygen than like ground-state dioxygen, so that knowl
edge of singlet-dioxygen chemistry facilitates an understanding and appreciation
of dioxygen biochemistry. The reactions of singlet dioxygen that may have
relevance to biological dioxygen metabolism are discussed thoroughly in Chapter
3. There are also many reactions of singlet dioxygen that have no relevance to
biological reactions at this time, but the potential importance of these reactions
to dioxygen metabolism dictates that they be included. These reactions are in
cluded as an addendum designated Chapter 21.
The discussion of triplet and singlet dioxygen is followed by a discussion
of the chemistry of the reduction products of dioxygen, superoxide ion and
peroxides. Superoxide dismutase and prostaglandins very naturally fit into these
chapters. The assumption is made that the reader is aware of the physiological
function of prostaglandins but wishes to know more about the chemistry and
biosynthesis. Discussions of catalases and peroxidases logically follow the chem
istry and biochemistry of peroxides. A familiarity with the enzyme intermediates
in catalase and peroxidase is helpful in the understanding of enzyme intermediates
in dioxygen reactions.
The discussion returns to dioxygen again to focus on the important problem
of activation. Activation by metals makes an easy transition to metal carriers
for dioxygen, both models and actual biological carriers.
Once dioxygen is activated, it can react in three different ways: (1) as a
one-, two-, or four-electron acceptor from the substrate; (2) as a two-electron
acceptor plus an oxygen atom donor; or (3) as a donor of two oxygen atoms.
These are discussed in order beginning with the four-electron oxidases. The two
electron-plus-oxygen-atom donors are called monooxygenases. These are clas
sified for discussion with respect to the cofactor involved: flavins, pterins, copper,
and iron. The monooxygenases are followed by the enzymes that donate two
oxygen atoms, the dioxygenases. The next two chapters discuss the special topics
of bioluminescence and toxicity, followed by the remainder of the singlet
dioxygen chemistry in Chapter 21.
lt is hoped that the reader will have time to read the whole book in order
to appreciate the complete story of dioxygen metabolism. However, this book
should be useful as a reference book when the reader desires information on a
given aspect of dioxygen chemistry or metabolism.
Lloyd L. Ingraham
Damon L. Meyer
Contents
1. Introduction 1
1.1 Chemical Reactions of Dioxygen ...................... 1
1.2 Biological Reactions of Dioxygen ...................... 2
1.3 Reduction Products of Dioxygen ....................... 3
1.4 Dioxygen Enzymes ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.5 Oxygen-17 Nuclear Magnetic Resonance Spectroscopy
of Oxygen ......................................... 4
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2. Ground-State Dioxygen 7
2.1 Properties of Dioxygen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.2 Reactions of Dioxygen ............................... 11
2.3 Chain Reactions of Dioxygen ......................... 13
2.4 Examples of Dioxygen Chain Reactions ................. 14
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3. Singlet Dioxygen 21
3.1 Physical Properties and Generation ..................... 21
3.2 Detection of Singlet Dioxygen . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.3 Organic Reactions of Singlet Dioxygen ................. 33
3.4 Singlet Dioxygen-Tocopherol Reaction ................. 36
3.5 Metathesis......................................... 36
3.6 Phototaxis ......................................... 38
3.7 Singlet Sigma Dioxygen ... . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Summary... . . ... . . . . . . . . . .. . . . . ... . . ... . . .... . . ... 40
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
4. Superoxide Ion 45
4.1 Properties, Sources, and Stability ...................... 45
4.2 Detection of Superoxide Ion .......................... 50
vii
viii CONTENTS
4.3 Haber-Weiss Reaction ............................... 51
4.4 Detection of 'OH Radicals ............................ 53
4.5 Reactions of Superoxide Ion with
Organic Compounds ................................. 55
4.6 Superoxide Dismutase ............................... 64
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
5. Dialkyl Peroxides 75
5.1 Introduction........................................ 75
5.2 Naturally Occurring Dialkyl Peroxides other than
Prostaglandin Intermediates ........................... 75
5.3 Prostaglandin....................................... 80
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
6. Catalases and Peroxidases 91
6.1 Catalase........................................... 91
6.2 Peroxidase......................................... 92
6.3 Mechanisms of Catalase and Peroxidase. . . . . . . . . . . . . . . . . 94
6.4 Chloroperoxidase ................................... 99
6.5 Glutathione Peroxidase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
7. Dioxygen as a Terminal Oxidant and the Formation
of Dioxygen 107
7.1 Fitness of Dioxygen as a Terminal Oxidant .............. 107
7.2 Formation of Dioxygen .............................. 110
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
8. Metal-Dioxygen Complexes 113
8.1 Metal-Dioxygen Bonding ............................ 113
8.2 Activation of Dioxygen .............................. 116
8.3 Classification of Metal-Dioxygen Complexes ............ 116
8.4 Bonding vs. Oxidation ............................... 118
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
9. Biological Iron Dioxygen Carriers 121
9.1 Hemoglobin and Myoglobin .......................... 121
9.2 Hemoglobin Models ................................. 125
9.3 Hemerythrin ....................................... 129
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
CONTENTS ix
10. Hemocyanin: A Biological Copper Dioxygen Carrier 135
10.1 General Properties ................................ 135
10.2 Hemocyanin Models. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
11. Oxidases 139
11.1 Introduction...................................... 139
11. 2 Laccase......................................... 139
11.3 Ceruloplasmin.................................... 140
11. 4 Ascorbic Acid Oxidase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
11. 5 Amine Oxidases .................................. 141
11.5.1 Monoamine Oxidase-Copper Enzyme ........ 141
11.5.2 Monoamine Oxidase-Flavin Enzyme ......... 142
11.5.3 Diamine Oxidase .......................... 142
11.6 Galactose Oxidase ................................ 143
11.7 Cytochrome Oxidase .............................. 144
11.8 Xanthine Oxidase... . . . . . .... . . ... . . ... .... . . .... . 145
11. 9 D-Amino Acid Oxidase ............................ 147
11.10 Glucose Oxidase .................................. 149
11.11 Lactate Oxidase .................................. 149
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
12. Flavin Monooxygenases 157
12.1 Introduction...................................... 157
12.2 Salicylate Hydroxylase ............................. 157
12.3 m-Hydroxybenzoate Hydroxylase .................... 158
12.4 m-Hydroxybenzoate 4-Hydroxylase ................... 158
12.5 p-Hydroxybenzoate Hydroxylase ..................... 159
12.6 Melilotic Hydroxylase ............................. 160
12.7 Phenol Hydroxylase ............................... 160
12.8 Orcinol Hydroxylase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
12.9 Kynurenine 3-Hydroxylase . . . . . . . . . . . . . . . . . . . . . . . . . . 160
12.10 Imidazoylacetate Monooxygenase .................... 161
12.11 Amine Oxidase ................................... 161
12.12 p-Cresol Methyl Hydroxylase ....................... 162
12.13 Mechanisms of Hydroxylation ....................... 162
12.14 Baeyer-Villiger Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . 168
12.15 Lactic Monooxygenase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
12.16 Lysine Monooxygenase ............................ 169
12.17 Arginine Monooxygenase . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
x CONTENTS
12.18 Oxalic Acid Oxidase 170
12.19 Mechanism of Oxidative Decarboxylation ............ . 170
References ...................................... . 171
13. Pterin Monooxygenases 175
13.1 Introduction ..................................... . 175
13.2 Phenylalanine Hydroxylase ........................ . 175
13.3 Tyrosine Hydroxylase ............................. . 177
References ...................................... . 178
14. Copper Hydroxylases 179
14.1 Tyrosine ... .................................... . 179
14.2 Dopamine-~-Hydroxylase ......................... . 181
References ...................................... . 182
15. Cytochrome P-450 185
15. 1 Properties .. .................................... . 185
15.2 Reaction Mechanisms ............................. . 187
15.3 Model Studies ................................... . 190
15.4 Oxides and Amine Dealkylation .................... . 191
References ...................................... . 193
16. Other Iron Monooxygenases 199
16.1 Heme Oxidation ................................. . 199
16.2 Tryptophan Side-Chain Oxidation ................... . 201
16.3 Indolyl-l,3-alkane a-Hydroxylase ................... . 201
References ...................................... . 201
17. Ribulose Bisphosphate Oxygenase 203
17. 1 Introduction ..................................... . 203
17.2 Chemical Analysis ............................... . 204
17.3 Effectors and Inhibitors ........................... . 205
17 .4 Reaction Mechanism ............................. . 205
References ...................................... . 208
18. Dioxygenases 211
18.1 Lipoxygenase ................................... . 211
18.2 Lipoxygenase Mechanism ......................... . 213
18.3 Other Lipoxygenases ............................. . 218
18.4 Prostaglandin Synthetase .......................... . 219
18.5 Pyrrolases ...................................... . 222
18.6 Tryptophan Dioxygenase .......................... . 223
