Table Of ContentMetabolism and Medicine
Foundations of Biochemistry and Biophysics
This textbook series focuses on foundational principles and experimental approaches across all areas of biological physics, covering
core subjects in a modern biophysics curriculum. Individual titles address such topics as molecular biophysics, statistical biophysics,
molecular modeling, single-molecule biophysics, and chemical biophysics. It is aimed at advanced undergraduate- and graduate-level
curricula at the intersection of biological and physical sciences. The goal of the series is to facilitate interdisciplinary research by train-
ing biologists and biochemists in quantitative aspects of modern biomedical research and to teach key biological principles to students
in physical sciences and engineering.
Authors are also welcome to contact the publisher (Physics Editor, Carolina Antunes: [email protected]) to discuss new
title ideas.
Light Harvesting in Photosynthesis
Roberta Croce, Rienk van Grondelle, Herbert van Amerongen, Ivo van Stokkum (Eds.)
An Introduction to Single Molecule Biophysics
Yuri L. Lyubchenko (Ed.)
Biomolecular Kinetics: A Step-by-Step Guide
Clive R. Bagshaw
Biomolecular Thermodynamics: From Theory to Application
Douglas E. Barrick
Quantitative Understanding of Biosystems: An Introduction to Biophysics
Thomas M. Nordlund
Quantitative Understanding of Biosystems: An Introduction to Biophysics, Second Edition
Thomas M. Nordlund, Peter M. Hoffmann
Entropy and Free Energy in Structural Biology: Thermodynamics, Statistical Mechanics And Computer Simulation
Hagai Meirovitch
Metabolism and Medicine: Two Volume Set
Brian Fertig
https://www.crcpress.com/Foundations-of-Biochemistry-and-Biophysics/book-series/CRCFOUBIOPHY
Metabolism and Medicine
The Physics of Biological Engines
Volume 1
Brian J. Fertig, M.D., F.A.C.E.
Associate Professor, Robert Wood Johnson Medical School
Chairman, Department of Diabetes & Endocrinology,
Hackensack Meridian Health @ JFK University Medical Center
Founder Diabetes & Osteoporosis Center, Piscataway, N.J.
Editorial Assistance by Jack Tuszynski, Ph.D.
First edition published 2022
by CRC Press
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and by CRC Press
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© 2022 Brian Fertig
CRC Press is an imprint of Taylor & Francis Group, LLC
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Library of Congress Cataloging-in-Publication Data
Names: Fertig, Brian, author.
Title: Metabolism and medicine / Brian Fertig, M.D., Robert Wood Johnson
Medical School, Department of Diabetes & Endocrinology Hackensack
Meridian, Health @ JFK University Medical Center.
Description: First edition. | Boca Raton : CRC Press, 2022. | Series:
Foundation of biochemistry and biophysics | Includes bibliographical
references and index.
Identifiers: LCCN 2021027983 (print) | LCCN 2021027984 (ebook) | ISBN
9780367699918 (hardback) | ISBN 9780367712259 (paperback) | ISBN
9781003149873 (ebook)
Subjects: LCSH: Metabolism--Disorders. | Human body--Microbiology.
Classification: LCC RC627.5 .F47 2022 (print) | LCC RC627.5 (ebook) | DDC
616.3/9--dc23
LC record available at https://lccn.loc.gov/2021027983
LC ebook record available at https://lccn.loc.gov/2021027984
ISBN: 9780367699918 (hbk)
ISBN: 9780367712259 (pbk)
ISBN: 9781003149873 (ebk)
DOI: 10.1201/9781003149873
Typeset in Times
by Deanta Global Publishing Services, Chennai, India
Dedicated to my wife, Eileen, and my son, Matthew,
without whom none of this would have even mattered.
Contents
Preface to Volume One .................................................................................................................................................................xiii
Prologue .......................................................................................................................................................................................xvii
Acknowledgments .........................................................................................................................................................................xxi
Author ..........................................................................................................................................................................................xxv
Personal Statements ...................................................................................................................................................................xxvii
1. Biological Thermodynamics: On Energy, Information, and Its Evil Twin, Entropy ......................................................1
Chapter Overview .....................................................................................................................................................................1
1.1 Introduction ...................................................................................................................................................................1
1.2 The Four Forces: Weak, Strong, Electromagnetic, and Gravitational; an Emphasis on the Weak Force ....................3
1.3 Energy in Its Various Forms .........................................................................................................................................6
1.4 Heat and Work ..............................................................................................................................................................7
1.5 The Birth of Thermodynamics .....................................................................................................................................7
1.6 Microscopic Origin of Entropy .....................................................................................................................................8
1.7 The Rule of Law in Physics: Energy Conservation ....................................................................................................10
1.8 The First and Second Laws of Thermodynamics .......................................................................................................11
1.9 Energy Cannot Be Created but Can Be Transformed ................................................................................................12
1.10 Heat, Entropy, and Energy Efficiency ........................................................................................................................13
1.11 Specific Heat ...............................................................................................................................................................13
1.12 Thermodynamics of Mechanical Engines ..................................................................................................................16
1.13 The Carnot Engine ......................................................................................................................................................19
1.14 Enthalpy and Internal Energy—Compared and Contrasted ......................................................................................20
1.15 Gibbs Free Energy and the Chemical Potential..........................................................................................................21
1.16 Thermodynamics of Biochemical Reactions ..............................................................................................................23
1.17 Information Energy .....................................................................................................................................................24
1.18 Thermodynamic Stability: Phase Transitions, Order Parameters, and Susceptibility Functions ..............................26
1.19 Expanded Concepts of Entropy and Information .......................................................................................................29
1.20 How Information Is Connected to Energy ..................................................................................................................30
1.21 Steady States and Homeostasis ...................................................................................................................................30
1.22 Structures and Their Functions ..................................................................................................................................32
1.23 Negative Entropy and Self-Organization ....................................................................................................................33
1.24 Biological Engines as Metaphors of the Carnot Engine .............................................................................................34
1.25 Metabolism: Life’s Necessity ......................................................................................................................................36
1.26 How Metabolism Is Linked to Aging .........................................................................................................................39
1.27 The Ultimate Source of Life’s Energy: Photosynthesis ..............................................................................................41
1.28 The Difference Between Quantum and Classical Metabolism May Be the Difference
Between Health and Disease ......................................................................................................................................41
1.29 Thermodynamic Processes in Metabolism.................................................................................................................42
1.30 Two Paths to Metabolic Energy Production ...............................................................................................................42
1.31 Inflammation, Pathogenesis, and Obesity ..................................................................................................................45
1.32 Ecological Symbiosis of Plants and Animals .............................................................................................................46
1.33 Metabolic Dysfunction and Disease States ................................................................................................................48
1.34 Inflammation, Toxicity, and Reactive Oxygen Species ..............................................................................................49
1.35 What Can Einstein’s Theories of Relativity Tell Us about Aging? ............................................................................49
1.36 Limitations of Scientific Reductionism and a Way out ..............................................................................................50
References ..............................................................................................................................................................................51
2. Biological Engines and the Molecular Machinery of Life ................................................................................................53
Chapter Overview ...................................................................................................................................................................53
2.1 Living Systems Viewed as Machines .........................................................................................................................53
2.2 Physical Forces in a Biological Context .....................................................................................................................53
2.3 Force and Energy Generation at the Organismic Level .............................................................................................54
vii
viii Contents
2.4 Cell Energetics: The Cell as a Machine ......................................................................................................................56
2.5 Cells’ Tensional Integrity: Tensegrity .........................................................................................................................57
2.6 The Mechanics of Cell Motion: Cell Motility ............................................................................................................59
2.7 Energy Production and Energy Transduction .............................................................................................................59
2.8 Mitochondria ...............................................................................................................................................................60
2.9 Chloroplasts ................................................................................................................................................................60
2.10 Osmotic Work .............................................................................................................................................................61
2.11 Energy and Material Transport in and out of a Cell ...................................................................................................62
2.11.1 Passive Transport ..........................................................................................................................................62
2.11.2 Active Transport............................................................................................................................................62
2.11.3 Ion Channels and Ion Pumps ........................................................................................................................62
2.12 The Cytoskeleton ........................................................................................................................................................63
2.13 Work During Cell Division: Chromosome Separation ...............................................................................................63
2.14 Microtubules ...............................................................................................................................................................64
2.15 Actin Filaments (Microfilaments)...............................................................................................................................65
2.16 Intermediate Filaments ...............................................................................................................................................65
2.17 The Quantum of Biological Energy: ATP ..................................................................................................................66
2.18 Molecular and Biological Machines: Motor Proteins .................................................................................................66
2.19 ATP Synthase ..............................................................................................................................................................68
2.20 The Myosin Family of Motors ....................................................................................................................................68
2.21 The Kinesin Family of Motors ...................................................................................................................................69
2.22 Dynein .........................................................................................................................................................................69
2.23 Energy Combustion Similarities between Cells and Automobiles .............................................................................69
2.24 Molecular Motors and the Laws of Thermodynamics ...............................................................................................71
2.25 Analogy between Mechanical and Biological Engines ..............................................................................................72
2.26 Biological Thermodynamics .......................................................................................................................................73
2.27 The Many Types of Biological Signals .......................................................................................................................75
2.28 Neuronal Signal Propagation ......................................................................................................................................76
2.29 Electromagnetic Energy across Scales of Biology .....................................................................................................78
2.29.1 Bioenergetics: The Davydov Soliton .............................................................................................................78
2.29.2 Biological Coherence: The Fröhlich Model ..................................................................................................78
2.30 Electrodynamic Interactions in Biology .....................................................................................................................81
2.31 Charge Transport ........................................................................................................................................................82
2.32 Electric Field Effects Present in Cells and Acting on Cells .......................................................................................82
2.33 Ionic Current Flows through Intra-Cellular Electrolytes ...........................................................................................82
2.34 Proton Transport .........................................................................................................................................................83
2.35 Electron Conduction and Tunneling ...........................................................................................................................83
2.36 Interactions of Biological Systems with Electromagnetic Radiation .........................................................................84
2.37 Bioelectricity and Biomagnetism ................................................................................................................................85
2.38 Biological Engines and the Quantum Biological Processes Explaining Cognition ...................................................86
2.39 Connections between Electricity, Magnetism, and Energy Generation .....................................................................88
2.40 Connections between Microtubules, Molecular Motors, and Mitochondria: Toward
a Molecular Explanation of Free Will ........................................................................................................................89
2.41 Collective Unconscious and Society ...........................................................................................................................91
References ..............................................................................................................................................................................91
3. From Quantum Biology to Quantum Medicine ................................................................................................................95
Chapter Overview ...................................................................................................................................................................95
3.1 On the Cusp of a Quantum Biology Revolution .........................................................................................................95
3.2 A Historical Perspective on Physics ...........................................................................................................................97
3.3 The Dawn of Quantum Biology ................................................................................................................................105
3.4 Decoherence..............................................................................................................................................................106
3.5 Quantum Weirdness and Biology .............................................................................................................................108
3.6 Can Objections to Quantum Biology Be Overcome? ...............................................................................................109
3.7 The Appeal of Quantum Mechanisms to Biology .....................................................................................................110
3.8 Biophotons: Light in Cells .........................................................................................................................................112
3.9 Quantum Nature of Vision, Olfaction, and Bird Navigation .....................................................................................114
3.10 Photosynthesis: Quantum Metabolism of Plants .......................................................................................................116
3.11 Quantum Metabolism ................................................................................................................................................118
Contents ix
3.12 Consequences of Quantum Metabolism ...................................................................................................................121
3.13 Synchronization of Cellular Activities .....................................................................................................................123
3.14 The Orchestra of Life: Biological Coherence ...........................................................................................................124
3.15 Biological Motors ......................................................................................................................................................126
3.16 Classical and Quantum Molecular Motors and the Laws of Thermodynamics .......................................................128
3.17 Energy and Information: A Marriage of Physics and Information Science in Biology ...........................................130
3.18 Classical and Quantum Information in Biology .......................................................................................................133
3.19 Aging and Senescence ..............................................................................................................................................138
3.19.1 Machine versus Biological Engine Analogy...............................................................................................139
3.19.2 Non-Redox Mediated Causes of Dysfunctional Oxidative Metabolism ....................................................140
3.19.3 Energy Transfer and Transformation of Information: Defense against Biological Aging ..........................141
3.20 Can Special Relativity Be of Relevance to Biology? .................................................................................................142
3.21 Information and Nutrition ..........................................................................................................................................143
3.22 Chemical Potential of Physical Biological Systems .................................................................................................150
3.23 Is Consciousness a Quantum Phenomenon? .............................................................................................................154
3.24 Brain’s Processing Power: How Many Flops and How Many Watts? ......................................................................156
3.25 The Human Brain: Its Structural Complexity and Amazing Efficiency ..................................................................157
3.26 The Neuron: Its Architecture and Central Role in the Brain’s Activities ................................................................159
3.27 The Special Role of Neuronal Microtubules and the Cytoskeleton .........................................................................159
3.28 Where Is Memory Stored in the Brain? ....................................................................................................................162
3.29 Are There Quantum Excitations in Microtubules?...................................................................................................162
3.30 Is Anesthesia a Quantum Process? ...........................................................................................................................163
3.31 Relevance of Quantum Biology to Health and Disease ............................................................................................164
3.32 The Feasibility of Encoding the Totality of the Human Experience and the Information Field of the Brain ..........167
3.33 An Integrated Perspective of Energy and Information Flow in Health and Disease ...............................................169
References .............................................................................................................................................................................176
4. From Systems Biology to Systems Medicine .....................................................................................................................181
Chapter Overview ..................................................................................................................................................................181
4.1 Problem Solving: Reductionism versus Simplifying Complexity .............................................................................181
4.2 Symmetries, Conservation Laws, and Symmetry Breaking ....................................................................................182
4.3 Systems: Open and Closed, Simple and Complex ....................................................................................................185
4.4 Stability, Biological Complexity, and Energy Flows ................................................................................................188
4.5 Implications for Clinical Practice .............................................................................................................................194
4.6 Framing Energy by the Creation of Time and Life, and by the Breaking of Symmetry .........................................195
4.7 Steady States, Attractor States, Strange Attractors, and Chaos ...............................................................................196
4.8 Nonlinear Interactions: Positive and Negative Feedback Loops ..............................................................................200
4.9 Why Life Exists: A Chaos Theory Perspective ........................................................................................................201
4.10 A Pedestrian Overview of Systems Biology .............................................................................................................201
4.11 Relevance of Chaos Theory to Human Biology .......................................................................................................202
4.12 Self-Organization and Self-Regulation .....................................................................................................................205
4.13 Playing Simple Games with Profound Implications: Cellular Automata .................................................................206
4.14 Biological Networks ..................................................................................................................................................207
4.15 Simplifying Complexity ...........................................................................................................................................209
4.16 The Limitations in Molecular Biology and Reductionism in Explaining the Living World .....................................210
4.17 Systems of Wholes and Parts .....................................................................................................................................211
4.18 Complexity and Information .....................................................................................................................................212
4.19 Nonlinearity, Bifurcations, and Phase Transitions ....................................................................................................214
4.20 A Biological Example: Metabolic Memory ...............................................................................................................216
4.21 Plus ça Change, Plus C’est la Même Chose ..............................................................................................................217
4.22 The Physics of Heat and the Biology of Inflammation: Are They Related? .............................................................219
4.23 Distinctions Between Homeostasis, Dynamic Equilibrium, and Steady States ......................................................223
4.24 Classes of Systems: Man-Made and Biological ........................................................................................................223
4.25 Application of Molecular Biology of Insulin Resistance and Type 2 Diabetes to Clinical Enigmas ......................224
4.26 Integrated Complexity of Systems Biology into an Optimally Functioning Whole ................................................225
4.27 Systems Theory: A Perspective ................................................................................................................................226
4.28 Chaos Theory ............................................................................................................................................................228
4.29 Complicated Systems and Complex Systems ...........................................................................................................228
4.30 Bottom-Up and Top-Down Approaches ...................................................................................................................233
