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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
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molecule biophysics, and chemical biophysics. It is aimed at advanced
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Light Harvesting in Photosynthesis
Roberta Croce, Rienk van Grondelle, Herbert van Amerongen, Ivo van
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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,
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Hagai Meirovitch
Metabolism and Medicine: Two Volume Set
Brian Fertig
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Metabolism and Medicine
The Metabolic Landscape of Health and Disease
Volume 2
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.
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 9780367699925
(hardback) | ISBN 9780367712297 (paperback) | ISBN 9781003149897 (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: 9780367699925 (hbk)
ISBN: 9780367712297 (pbk)
ISBN: 9781003149897 (ebk)
DOI: 10.1201/9781003149897
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
Prologue
Acknowledgments
Author
Personal Statements
1. Introduction to Metabolism: A New Model for Medicine
Abbreviations
1.1 Brief History of Metabolism and the Complex Personalities
of the Scientists Who Shaped It
1.2 Opening Remarks
(Biology, Introductory Level)
1.3 Metabolism Fuels Biological Motors and Engines
(Physics, Introductory Level)
(Biology/Biological Chemistry, Clinical Level)
1.4 Metabolic Pathways and Cellular Respiration
(Biological Chemistry, Introductory Level)
1.4.1 Metabolic Modes of Energy Production
(Physics and Quantum Biology Introductory Level)
1.4.2 Metabolic Cycles and Metabolic Rate
(Biological Metabolism and Translational Medicine,
Introductory Level)
(Physics Metabolism and Translational Medicine,
Introductory/Intermediate Level)
(Biological Chemistry and Translational
Medicine,Introductory/Intermediate Level)
1.4.3 Metabolic Rate, Metabolic Efficiency, and Cellular
Respiration in Clinical Medicine
(Clinical Biological Physiology/Exercise Physiology,
Introductory Level)
1.5 Biological Entropy Production Rate and Aging
(Biophysics, Metabolism, and Physiology, Introductory
Level)
1.5.1 Biological Entropy Production Rate and
Pharmacological Implications
(Metabolism and Translational Medicine, Introductory
Level)
1.6 Key Bioenergetics Concepts
(Basic Concept of Metabolism, Introductory Level)
1.7 Dysfunction in Electron Transport System, Mitochondrial
Function, and its Importance in Chronic Disease
(Metabolism and Physiology, Translational Medicine,
Introductory Level)
1.7.1 Biochemistry of the Electron Transport System
(Biochemistry, Medium Difficulty)
Basics of the Electron Transport Chain
1.7.2 Biochemical Characteristics of Electron Transport
Chain Dysfunction
(Mechanism of ROS Generation Through ETC,
Introductory Level)
1.7.3 Clinical Perspective of Electron Transport System
Dysfunction
(Mitochondrial Dysfunction, Metabolic Homeostasis,
and Onset of Chronic Diseases of Aging, Clinical Level)
1.7.4 Influence of Glucose and Lipid Metabolism on the
Function of the Electron Transport System
(Biochemistry, Intermediate Level)
1.7.5 Redox Potential and Its Importance in Biochemical
Reactions
1.7.6 Clinical Application and Examples of Redox State to
Insulin Resistance and Type 2 Diabetes
1.7.7 Contributions of Macronutrients to Redox Potential,
Proton Motive Force, and Oxidative Stress
1.7.8 Elevated Fatty Acid Metabolism and Its Relevance in
Aging and Chronic Diseases
1.7.9 Targeting the Electron Transport System for the
Treatments of Metabolic Disease
1.7.9.1 Improving Mitochondrial Metabolism
1.7.9.2 Manipulation of Mitochondrial Redox System
for Therapeutic Implications: Pharmacologic
Intervention
1.7.10 Conclusion
1.8 Ketone Bodies in Metabolism in Health and Disease
(Metabolism and Physiology, Ketones, Introductory Level)
1.8.1 Ketone Bodies are “Super Fuels” and Electron
Scavengers
1.8.2 Role of Ketone Bodies in Starvation
(Molecular Biology, Intermediate Level)
1.8.3 Benefits and Dangers of Ketosis in Diabetes
(Molecular Biology, Intermediate Level)
1.8.4 Potential Benefits of Ketosis in Non-Diabetic Diseases
(Biochemistry, Introductory Level)
1.8.5 Yin-Yang Perspectives on Ketone Body Metabolism
(Biochemistry, Intermediate Level)
1.8.6 Conclusions
1.9 Energy Sensors and Fuel Gauges
(Metabolic Physiology and Translational Medicine,
Introductory Level)
1.9.1 Energy Sensors, Circadian Biology, and Metabolic
Homeostasis
(Metabolic Physiology and Circadian Biology,
Translational Medicine, Intermediate Level)
1.9.2 Parameters of Diet and an ETC Mechanistic Model of
Human Metabolic Health and Disease
(Circadian Biology and Translational Medicine,
Introductory Level)
1.10 The Genesis of Accelerated Aging and Chronic Diseases of
Aging
(Clinical Pathophysiology, Introductory Level)
1.10.1 Insulin Resistance, Diet, Peripheral Clocks, and
Metabolism
(Metabolism, Circadian Biology, Clinical Physiology,
and Pathophysiology, Introductory Level)
1.10.2 Insulin Resistance and Hyperinsulinemia: The
Chicken or the Egg?
(Metabolic Physiology, Introductory Level)
1.10.3 The Protective Role of Visceral Adiposity
(Obesity, Translational Medicine)
1.10.4 Loss of or Lipolysis of VAT and Autonomic
Dysfunction: An Unrecognized Parameter of Premature
Chronic Disease and Mortality
(Obesity, Translational Medicine)
1.10.5 An Anecdote for Current Times: Obesity and SARS-
CoV-2 in Pulmonary Fibrosis
1.10.6 Endotoxicosis and Insulin Resistance
1.10.7 Visceral Adiposity at the Intersection of an
Inflammatory Diet and Insulin Resistance
(Clinical Metabolism, Translational Medicine)
1.11 Models of Chronic Diseases in Medicine as Metabolic
Disorders
(Clinical Metabolism/Translational Medicine)
1.11.1 The Warburg Effect: A Modern Perspective of an Old
Hypothesis
1.11.2 An Extension of Brownlee’s Unifying Hypothesis
1.11.3 The Warburg Effect and the Extension of the Unifying
Hypothesis: A Broader Unifying Pathobiology
1.12 Concluding Remarks
References
2. The Stress Response: From Health to Disease
Abbreviations
Chapter Overview
2.1 What Is Stress?
2.1.1 The Interdisciplinary Nature of Stress
2.2 The Stress Response
2.2.1 Homeostasis, Allostatic Load, and Allostatic Overload
2.2.2 The Stress Paradox
2.2.2.1 The Impact of Social Networks on the Stress
Paradox
2.2.2.2 A Clinical Example of the Stress Paradox
2.2.3 Stress through the Physiological Fitness Landscape
2.2.4 The Effects of Stress on Synchronized Physiology and
Metabolism
2.3 A Modern-Day Stress Response Model
2.3.1 The Metabolic Demand of Stress
2.3.2 The Uncertainty Reduction Model
2.4 The Neural Circuitry of Stress
2.4.1 Interconnections
2.4.2 Neuroendocrine Response to Stress and Insulin
Resistance
2.4.3 Stress and Norepinephrine
2.4.4 The Neural Circuitry of Uncertainty
2.4.5 Uncertainty and Chronic Anxiety
2.4.6 The Neural Circuitry of Energy Expenditure under
Stress
2.5 Motivation and Reward
2.5.1 The Neural Circuitry of Reward
2.5.2 The Reward Circuitry, Stress, and the Uncertainty
Model
2.5.3 Gender Differences in Response to Stressors
2.5.4 Possible Interventions for Addictions
2.6 Synaptic Plasticity
