Preface ........................................................ xv
Acknowledgments .............................................. xvii
The Authors ................................................... xix
SECTION I
Introduction
Chapter 1 Molecular Biology of Omega-3 Chains as Structural
Lipids: Many Central Questions Remain Unanswered ..... 3
1.1 Membrane Lipids: Contribution to Ecology ................... 6
1.2 Extraordinary Conformational Dynamics of DHA Predicts
Extraordinary Functions and Vice Versa ..................... 8
1.3 Reductionist Strategy for DHA Research .................... 10
Selected Bibliography .......................................... 12
SECTION II
Evolution of DHA and the Membrane
Chapter 2 Darwinian Selection of the Fittest Membrane
Lipids: From Archaeal Isoprenoids to DHA-Enriched
Rhodopsin Disks ..................................... 17
2.1 Bioenergetics as the Driver of Evolution of Lipid
Structures ................................................ 19
2.2 Do Archaea Have an Achilles' Heel? ........................ 21
2.3 DHA Drives Motion to New Speeds: Evolution of Membranes
for Vision ................................................ 24
2.4 Summary ................................................... 27
Selected Bibliography .......................................... 28
Chapter 3 Coevolution of DHA Membranes and Their Proteins ..... 31
3.1 Did Motion or Lack of Motion Prevail in Membranes of
ProtoCells? ............................................... 31
3.2 Which Came First—Proteins or Membranes? ................... 32
3.3 Ionophores Behave as Primitive Transporters and Some
Depend on the Physical State of the Membrane .............. 33
3.4 Many Archaeal Membrane Proteins Are Laterally Immobile,
but Some Can Spin ......................................... 36
3.5 Sensory Perception Requires Membrane Lateral Motion ....... 38
3.6 Does Rhodopsin Move Faster in a DHA (22:6) versus DPA
(22:5) Bilayer? ........................................... 39
3.7 DHA Phospholipids Liberate Membrane Enzymes / Substrates
Trapped in Lipid Rafts .................................... 40
3.8 Have Some Membrane-Bound Enzymes Evolved Dependence on
a Fluid Lipid Environment for Biocatalysis? ............... 40
3.9 Phospholipid-Dependent Enzymes ............................ 41
3.10 DHA as a Space-Filling Sealant around Membrane
Proteins ................................................. 41
3.11 Summary .................................................. 43
Selected Bibliography .......................................... 44
Chapter 4 Convergent Evolution of DHA/EPA Biosynthetic
Pathways ............................................ 47
4.1 Domain Analysis of DHA/EPA Gene Clusters .................. 48
4.2 The PKS Pathway ........................................... 50
4.3 Mechanism of Specificity .................................. 52
4.4 Summary ................................................... 53
Selected Bibliography .......................................... 54
Chapter 5 Membrane Evolution in a Marine Bacterium:
Capitalizing on DHA for Energy Conservation in
Seawater ............................................ 55
5.1 Energy Limitation Plagues the Life of a Deep-Sea
Bacterium ................................................. 55
5.2 Moritella Has Evolved Powerful Na+ Efflux Pumps ........... 57
5.3 DHA/EPA Synthesis Is Osmoregulated ........................ 60
5.4 DHA Conformational Dynamics Fit to Functions Needed
in the Deep Sea ........................................... 62
5.5 Summary ................................................... 65
Selected Bibliography .......................................... 66
Chapter 6 Evolution of DHA Membranes in Human Neurons ......... 69
6.1 DHA May Reduce Na+ Leakage into Neurons ................... 71
6.2 Do DHA Plasmalogens Shield Cations? ....................... 73
6.3 Importance of Motion ...................................... 74
6.4 Case Histories ............................................ 74
6.5 Summary ................................................... 79
Selected Bibliography .......................................... 79
SECTION III
General Properties of Omega-3s and Other Membrane Lipids
Chapter 7 DHA/EPA Chains as Powerful Membrane Antifreeze ...... 83
7.1 Survey of Phospholipids Based on Phase Transition
Temperatures .............................................. 85
7.2 Ecological Distribution of Phospholipids with Ultralow
Phase Transition Temperatures ............................. 86
7.3 Calibrating the Fluidizing Power of Fatty Acids ........... 87
7.4 Seeding Model of DHA in Disrupting Lipid Rafts ............ 91
7.5 Summary ................................................... 92
Selected Bibliography .......................................... 92
Chapter 8 DHA as a Mediocre Permeability Barrier against
Cations: Water Wire Theory ........................... 95
8.1 A Membrane-Spanning Nanotube Formed by an Antibiotic
Creates a Molecular Thread of Water That Conducts
Protons at Amazing Rates .................................. 96
8.2 Water Wires Likely Form Spontaneously in Membranes ........ 98
8.3 DHA and Water Wires ...................................... 100
8.4 Fatty Acid Bulking for "Plugging the Proton Dike" ........ 101
8.5 Summary .................................................. 105
Selected Bibliography ......................................... 106
Chapter 9 DHA/EPA Membranes as Targets of Oxidative
Damage ............................................. 107
9.1 Brief Chemistry of Lipoxidation of DHA/EPA Membranes ..... 108
9.2 DHA Might Be Toxic to E. coli ............................ 1ll
9.3 Growth of EPA Recombinants of E. coli Indicates 02
Toxicity in Vivo ......................................... 112
9.4 Yeast (Saccharomyces cerevisiae) Synthesizes Only
Monounsaturated Chains and Feeding These Cells
Polyunsaturated Chains Can Be Toxic ...................... 113
9.5 C. elegans Produces EPA and Seeks or Creates Low 02
Environments ............................................. 113
9.6 Birds .................................................... 114
9.7 Humans: Rhodopsin Disk Membranes Are Highly Enriched
with DHA, Oxidize Rapidly, and Require Continuous
Renewal .................................................. 115
9.8 Summary .................................................. 116
Selected Bibliography ......................................... 117
SECTION IV
Cellular Biology of OmegaSs and Other Membrane Lipids
Chapter 10 Bacteria: Environmental Modulation of Membrane
Lipids for Bioenergetic Gain ....................... 121
10.1 Methyl-Branched Fatty Acids as Membrane Bulking
Agents ................................................... 122
10.2 Trans Fatty Acids Play Multiple Beneficial Roles ......... 123
10.3 Cis-Vaccenic Acid Conformation Enables Energy-
Transducing Membranes Dependent on Cholesterol-Like
Molecules ................................................ 126
10.4 Bacteria Might Produce Plasmalogens as H+/Na+
Blockers ................................................. 130
10.5 DHA as a Virulence Factor in a Fish Pathogen? ............ 132
10.6 Summary .................................................. 133
Selected Bibliography ......................................... 134
Chapter 11 Chloroplasts: Harnessing DHA/EPA for Harvesting
Light in the Sea ................................... 135
11.1 Long-Distance Electron Transport as a Rate-Limiting
Step in Photosynthesis ................................... 138
11.2 Speeding up Long-Distance Electron Transport ............. 139
11.3 A Delicate Balancing Act between Proton Permeability,
Motion, and Oxidative Stability .......................... 142
11.4 Summary .................................................. 143
Selected Bibliography ......................................... 143
Chapter 12 Mitochondria: DHA-Cardiolipin Boosts Energy
Output ............................................. 145
12.1 Making a Case for DHA-Cardiolipin in Fast Muscles ........ 145
12.2 Possible Biochemical Roles of DHA Cardiolipin ............ 148
12.3 Cardiolipin Case Histories ............................... 150
12.4 Natural Doping with DHA/EPA for Endurance Flight ......... 153
12.5 Summary .................................................. 154
Selected Bibliography ......................................... 156
Chapter 13 Sperm: Essential Roles of DHA Lead to Development
of a Mechanical Stress Hypothesis .................. 157
13.1 Surprise Number One: DHA Is Localized in Tail
Membranes ................................................ 158
13.2 Surprise Number Two: Low 02 Levels in the Female
Reproductive Tract Protect DHA from Oxidation ............ 160
13.3 Surprise Number Three: Motion Is Energized by Sugar,
a Weak Energy Source, Rather than Mitochondria ........... 161
13.4 Surprise Number Four: Sperm Tail Membranes Are
Excitatory in Nature and Must Expend Considerable
Energy for Maintaining Na+/K+ Balance .................... 161
13.5 Surprise Number Five: Dynamic Space-Filling
Conformation of DHA ...................................... 162
13.6 Surprise Number Six: Lessons from Sperm Applied to
Neurosensory Cilia and Other Mechano-Sensitive
Membranes ................................................ 164
13.7 Surprise Number Seven: Gender Determination Influenced
by Diet? ................................................. 166
13.8 Summary .................................................. 167
Selected Bibliography ......................................... 168
SECTION V Lessons and Applications
Chapter 14 DHA/EPA Mutualism between Bacteria and Marine
Animals ............................................ 171
14.1 Gastrointestinal Tract of Fish Is a Suitable Habitat
for DHA/EPA Mutualism .................................... 171
14.2 DHA/EPA-Producing Bacteria Inhabit the Intestinal
Tracts of Certain Marine Fish and Mollusks ............... 175
14.3 Mechanisms for Release of DHA/EPA to Benefit the
Host ..................................................... 176
14.4 Summary .................................................. 179
Selected Bibliography ......................................... 179
Chapter 15 Membrane Adaptations for an Oily Environment:
Lessons from a Petroleum-Degrading Bacterium ....... 181
15.1 Genomic Analysis Reveals that Na+ Bioenergetics Evolved
as a Mechanism to Marginalize Proton Leakage Caused by
Petroleum ................................................ 182
15.2 Outer Membrane (OM) Lipid Structure as a Physical
Barrier against Oil ...................................... 185
15.3 Other Changes ............................................ 186
15.4 Ecological Support ....................................... 186
15.5 Summary .................................................. 187
Selected Bibliography ......................................... 188
Chapter 16 Lessons from Yeast: Phospholipid Conformations
Are Important in Winemaking ........................ 189
16.1 Discovery and Roles of Asymmetrical Phospholipids in
Yeast .................................................... 189
16.2 Membrane Alterations Accompanying Fermentation ........... 191
16.3 Energy Uncoupling in the Plasma Membrane of Yeast Is
Advantageous in Nature ................................... 191
16.4 Water Wire Theory Can Explain Uncoupling in Yeast ........ 192
16.5 Summary .................................................. 194
Selected Bibliography ......................................... 194
Chapter 17 DHA Principle Applied to Global Warming ............ 197
17.1 Marine Productivity Is Threatened by Even Modest
Thermal Upshocks ......................................... 197
17.2 Highly Unsaturated Membranes of Symbiotic Algae of
Corals Have Already Been Implicated as "Reporters" of
Global Warming ........................................... 199
17.3 Thermal Killing of DHA-Producing Bacteria as a
Surrogate for Marine Chloroplasts ........................ 200
17.4 Conformational Model ..................................... 202
17.5 DHA/EPA Are Needed to Build Efficient Neurosensory
Membranes in Zooplankton and Other Marine Animals ........ 204
17.6 Summary .................................................. 206
Selected Bibliography ......................................... 207
Chapter 18 DHA Principle Applied to Molecular Farming ......... 209
18.1 Asilomar Conference in 1975 on Recombinant DNA Ushered
in the Era of Genetically Engineered Crop Plants ......... 210
18.2 DHA Is Currently Produced from Marine Algae, but Crop
Plants Are Being Considered .............................. 211
18.3 DHA Produced by Land Plants Is Predicted to Be Its
Own Worst Enemy .......................................... 212
18.4 Photo-Protection Might Be Needed ......................... 214
18.5 Summary .................................................. 216
Selected Bibliography ......................................... 217
Chapter 19 DHA/Unsaturation Theory of Aging ................... 219
19.1 DHA Content Predicts Long Life Span of Naked Mole Rats
and Short Life of Mice ................................... 219
19.2 Unsaturation Theory Applied to Insects ................... 222
19.3 Lipoxidation Mechanisms .................................. 222
19.4 Lipoxidation Products Might Directly Uncouple Cation
Gradients in Mitochondria and Create Energy Stress ....... 223
19.5 Integrating Energy Stress Caused by the Plasma
Membrane into the Aging Cascade(s) ....................... 224
19.6 Summary .................................................. 225
Selected Bibliography ......................................... 226
Chapter 20 DHA Principle Applied to Neurodegenerative
Diseases ........................................... 227
20.1 DHA as a Risk Factor in Aging Neurons .................... 227
20.2 Drop in DHA Levels as a Disease Marker and Relationship
to Energy Stress ......................................... 231
20.3 Toxic Peptides as Energy Uncouplers? ..................... 233
20.4 Consideration of Neurodegenerative Diseases as Membrane
Diseases ................................................. 235
20.5 Summary .................................................. 237
Selected Bibliography ......................................... 238
Chapter 21 Dietary DHA in Prevention of Colon Cancer: How
a Risk to the Cell Benefits the Organism ........... 241
21.1 Nature of Colon Cancer ................................... 241
21.2 Dietary DHA Targeted to Mitochondrial Cardiolipin of
Colon Cells .............................................. 243
21.3 Oxidation of DHA Cardiolipin as a Trigger of Apoptosis ... 244
21.4 Summary .................................................. 245
Selected Bibliography ......................................... 245
Index ......................................................... 247
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