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- ISBN: 9781439812990 | 1439812993
- Cover: Hardcover
- Copyright: 12/3/2009
The physical-chemical properties of the omega-3 fatty acid DHA (docosahexaenoic acid) enable it to facilitate biochemical processes in the membrane. This effect has numerous benefits, including those involved in the growth of bacteria, rapid energy generation, human vision, brain impulse, and photosynthesis, to name a few. Yet DHA also carries risks that can lead to cellular death and disease. Omega-3 Fatty Acids and the DHA Principle explores the roles of omega-3 fatty acids in cellular membranes ranging from human neurons and swimming sperm to deep sea bacteria, and develops a principle by which to assess their benefits and risks.
Preface | p. xv |
Acknowledgments | p. xvii |
The Authors | p. xix |
Introduction | |
Molecular Biology of Omega-3 Chains as Structural Lipids: Many Central Questions Remain Unanswered | p. 3 |
Membrane Lipids: Contribution to Ecology | p. 6 |
Extraordinary Conformational Dynamics of DHA Predicts Extraordinary Functions and Vice Versa | p. 8 |
Reductionist Strategy for DHA Research | p. 10 |
Selected Bibliography | p. 12 |
Evolution of DHA and the Membrane | |
Darwinian Selection of the Fittest Membrane Lipids: From Archaeal Isoprenoids to DHA-Enriched Rhodopsin Disks | p. 17 |
Bioenergetics as the Driver of Evolution of Lipid Structures | p. 19 |
Do Archaea Have an Achilles' Heel? | p. 21 |
DHA Drives Motion to New Speeds: Evolution of Membranes for Vision | p. 24 |
Summary | p. 27 |
Selected Bibliography | p. 28 |
Coevolution of DHA Membranes and Their Proteins | p. 31 |
Did Motion or Lack of Motion Prevail in Membranes of ProtoCells? | p. 31 |
Which Came First-Proteins or Membranes? | p. 32 |
Ionophores Behave as Primitive Transporters and Some Depend on the Physical State of the Membrane | p. 33 |
Many Archaeal Membrane Proteins Are Laterally Immobile, but Some Can Spin | p. 36 |
Sensory Perception Requires Membrane Lateral Motion | p. 38 |
Does Rhodopsin Move Faster in a DHA (22:6) versus DPA (22:5) Bilayer? | p. 39 |
DHA Phospholipids Liberate Membrane Enzymes/ Substrates Trapped in Lipid Rafts | p. 40 |
Have Some Membrane-Bound Enzymes Evolved Dependence on a Fluid Lipid Environment for Biocatalysis? | p. 40 |
Phospholipid-Dependent Enzymes | p. 41 |
DHA as a Space-Filling Sealant around Membrane Proteins | p. 41 |
Summary | p. 43 |
Selected Bibliography | p. 44 |
Convergent Evolution of DHA/EPA Biosynthetic Pathways | p. 47 |
Domain Analysis of DHA/EPA Gene Clusters | p. 48 |
The PKS Pathway | p. 50 |
Mechanism of Specificity | p. 52 |
Summary | p. 53 |
Selected Bibliography | p. 54 |
Membrane Evolution in a Marine Bacterium: Capitalizing on DHA for Energy Conservation in Seawater | p. 55 |
Energy Limitation Plagues the Life of a Deep-Sea Bacterium | p. 55 |
Moritella Has Evolved Powerful Na+ Efflux Pumps | p. 57 |
DHA/EPA Synthesis is Osmoregulated | p. 60 |
DHA Conformational Dynamics Fit to Functions Needed in the Deep Sea | p. 62 |
Summary | p. 65 |
Selected Bibliography | p. 66 |
Evolution of DHA Membranes in Human Neurons | p. 69 |
DHA May Reduce Na+ Leakage into Neurons | p. 71 |
Do DHA Plasmalogens Shield Cations? | p. 73 |
Importance of Motion | p. 74 |
Case Histories | p. 74 |
Summary | p. 79 |
Selected Bibliography | p. 79 |
General Properties of Omega-3s and Other Membrane Lipids | |
DHA/EPA Chains as Powerful Membrane Antifreeze | p. 83 |
Survey of Phospholipids Based on Phase Transition Temperatures | p. 85 |
Ecological Distribution of Phospholipids with Ultralow Phase Transition Temperatures | p. 86 |
Calibrating the Fluidizing Power of Fatty Acids | p. 87 |
Seeding Model of DHA in Disrupting Lipid Rafts | p. 91 |
Summary | p. 92 |
Selected Bibliography | p. 92 |
DHA as a Mediocre Permeability Barrier against Cations: Water Wire Theory | p. 95 |
A Membrane-Spanning Nanotube Formed by an Antibiotic Creates a Molecular Thread of Water That Conducts Protons at Amazing Rates | p. 96 |
Water Wires Likely Form Spontaneously in Membranes | p. 98 |
DHA and Water Wires | p. 100 |
Fatty Acid Bulking for "Plugging the Proton Dike" | p. 101 |
Summary | p. 105 |
Selected Bibliography | p. 106 |
DHA/EPA Membranes as Targets of Oxidative Damage | p. 107 |
Brief Chemistry of Lipoxidation of DHA/EPA Membranes | p. 108 |
DHA Might Be Toxic to E. coli | p. 111 |
Growth of EPA Recombinants of E. coli Indicates O2 Toxicity in Vivo | p. 112 |
Yeast (Saccharomyces cerevisiae) Synthesizes Only Monounsaturated Chains and Feeding These Cells Polyunsaturated Chains Can Be Toxic | p. 113 |
C. elegans Produces EPA and Seeks or Creates Low O2 Environments | p. 113 |
Birds | p. 114 |
Humans: Rhodopsin Disk Membranes are Highly Enriched with DHA, Oxidize Rapidly, and Require Continuous Renewal | p. 115 |
Summary | p. 116 |
Selected Bibliography | p. 117 |
Cellular Biology of Omega-3s and Other Membrane Lipids | |
Bacteria: Environmental Modulation of Membrane Lipids for Bioenergetic Gain | p. 121 |
Methyl-Branched Fatty Acids as Membrane Bulking Agents | p. 122 |
Trans Fatty Acids Play Multiple Beneficial Roles | p. 123 |
Cis-Vaccenic Acid Conformation Enables Energy-Transducing Membranes Dependent on Cholesterol-Like Molecules | p. 126 |
Bacteria Might Produce Plasmalogens as H+/Na+ Blockers | p. 130 |
DHA as a Virulence Factor in a Fish Pathogen? | p. 132 |
Summary | p. 133 |
Selected Bibliography | p. 134 |
Chloroplasts: Harnessing DHA/EPA for Harvesting Light in the Sea | p. 135 |
Long-Distance Electron Transport as a Rate-Limiting Step in Photosynthesis | p. 138 |
Speeding up Long-Distance Electron Transport | p. 139 |
A Delicate Balancing Act between Proton Permeability, Motion, and Oxidative Stability | p. 142 |
Summary | p. 143 |
Selected Bibliography | p. 143 |
Mitochondria: DHA-Cardiolipin Boosts Energy Output | p. 145 |
Making a Case for DHA-Cardiolipin in Fast Muscles | p. 145 |
Possible Biochemical Roles of DHA Cardiolipin | p. 148 |
Cardiolipin Case Histories | p. 150 |
Natural Doping with DHA/EPA for Endurance Flight | p. 153 |
Summary | p. 154 |
Selected Bibliography | p. 156 |
Sperm: Essential Roles of DHA Lead to Development of a Mechanical Stress Hypothesis | p. 157 |
Surprise Number One: DHA Is Localized in Tail Membranes | p. 158 |
Surprise Number Two: Low O2 Levels in the Female Reproductive Tract Protect DHA from Oxidation | p. 160 |
Surprise Number Three: Motion is Energized by Sugar, a Weak Energy Source, Rather than Mitochondria | p. 161 |
Surprise Number Four: Sperm Tail Membranes Are Excitatory in Nature and Must Expend Considerable Energy for Maintaining Na+/K+ Balance | p. 161 |
Surprise Number Five: Dynamic Space-Filling Conformation of DHA | p. 162 |
Surprise Number Six: Lessons from Sperm Applied to Neurosensory Cilia and Other Mechano-Sensitive Membranes | p. 164 |
Surprise Number Seven: Gender Determination Influenced by Diet? | p. 166 |
Summary | p. 167 |
Selected Bibliography | p. 168 |
Lessons and Applications | |
DHA/EPA Mutualism between Bacteria and Marine Animals | p. 171 |
Gastrointestinal Tract of Fish is a Suitable Habitat for DHA/EPA Mutualism | p. 171 |
DHA/EPA-Producing Bacteria Inhabit the Intestinal Tracts of Certain Marine Fish and Mollusks | p. 175 |
Mechanisms for Release of DHA/EPA to Benefit the Host | p. 176 |
Summary | p. 179 |
Selected Bibliography | p. 179 |
Membrane Adaptations for an Oily Environment: Lessons from a Petroleum-Degrading Bacterium | p. 181 |
Genomic Analysis Reveals that Na+ Bioenergetics Evolved as a Mechanism to Marginalize Proton Leakage Caused by Petroleum | p. 182 |
Outef Membrane (OM) Lipid Structure as a Physical Barrier against Oil | p. 185 |
Other Changes | p. 186 |
Ecological Support | p. 186 |
Summary | p. 187 |
Selected Bibliography | p. 188 |
Lessons from Yeast: Phospholipid Conformations are Important in Winemaking | p. 189 |
Discovery and Roles of Asymmetrical Phospholipids in Yeast | p. 189 |
Membrane Alterations Accompanying Fermentation | p. 191 |
Energy Uncoupling in the Plasma Membrane of Yeast is Advantageous in Nature | p. 191 |
Water Wire Theory Can Explain Uncoupling in Yeast | p. 192 |
Summary | p. 194 |
Selected Bibliography | p. 194 |
DHA Principle Applied to Global Warming | p. 197 |
Marine Productivity is Threatened by Even Modest Thermal Upshocks | p. 197 |
Highly Unsaturated Membranes of Symbiotic Algae of Corals Have Already Been Implicated as "Reporters" of Global Warming | p. 199 |
Thermal Killing of DHA-Producing Bacteria as a Surrogate for Marine Chloroplasts | p. 200 |
Conformational Model | p. 202 |
DHA/EPA Are Needed to Build Efficient Neurosensory Membranes in Zooplankton and Other Marine Animals | p. 204 |
Summary | p. 206 |
Selected Bibliography | p. 207 |
DHA Principle Applied to Molecular Farming | p. 209 |
Asilomar Conference in 1975 on Recombinant DNA Ushered in the Era of Genetically Engineered Crop Plants | p. 210 |
DHA is Currently Produced from Marine Algae, but Crop Plants Are Being Considered | p. 211 |
DHA Produced by Land Plants is Predicted to Be Its Own Worst Enemy | p. 212 |
Photo-Protection Might Be Needed | p. 214 |
Summary | p. 216 |
Selected Bibliography | p. 217 |
DHA/Unsaturation Theory of Aging | p. 219 |
DHA Content Predicts Long Life Span of Naked Mole Rats and Short Life of Mice | p. 219 |
Unsaturation Theory Applied to Insects | p. 222 |
Lipoxidation Mechanisms | p. 222 |
Lipoxidation Products Might Directly Uncouple Cation Gradients in Mitochondria and Create Energy Stress | p. 223 |
Integrating Energy Stress Caused by the Plasma Membrane into the Aging Cascade(s) | p. 224 |
Summary | p. 225 |
Selected Bibliography | p. 226 |
DHA Principle Applied to Neurodegenerative Diseases | p. 227 |
DHA as a Risk Factor in Aging Neurons | p. 227 |
Drop in DHA Levels as a Disease Marker and Relationship to Energy Stress | p. 231 |
Toxic Peptides as Energy Uncouplers? | p. 233 |
Consideration of Neurodegenerative Diseases as Membrane Diseases | p. 235 |
Summary | p. 237 |
Selected Bibliography | p. 238 |
Dietary DHA in Prevention of Colon Cancer: How a Risk to the Cell Benefits the Organism | p. 241 |
Nature of Colon Cancer | p. 241 |
Dietary DHA Targeted to Mitochondrial Cardiolipin of Colon Cells | p. 243 |
Oxidation of DHA Cardiolipin as a Trigger of Apoptosis | p. 244 |
Summary | p. 245 |
Selected Bibliography | p. 245 |
Index | p. 247 |
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