The Hidden Mechanics of Exercise The Hidden Mechanics of Exercise Molecules That Move Us Christopher M. Gillen THE BELKNAP PRESS OF HARVARD UNIVERSITY PRESS Cambridge, Massachusetts London, En gland 2014 Copyright © 2014 by the President and Fellows of Harvard College All rights reserved Printed in the United States of America Library of Congress Cataloging- in- Publication Data Gillen, Christopher M., author. The hidden mechanics of exercise : molecules that move us / Christopher M. Gillen. pages cm Includes bibliographical references and index. ISBN 978-0- 674-72494- 5 (alk. paper) 1. Exercise—Physiological aspects. 2. Exercise—Molecular aspects. 3. Human mechanics. 4. Kinesiology. I. Title. QP303.G543 2014 612.7'6—dc23 2013034257 I dedicate this book to my mother and father, who inspired me to exercise my mind, body, and spirit. Contents Prologue: Molecules in Motion 1 1. Function Follows Form 12 2. An Experiment of One 33 3. The Gene for Gold Medals 54 4. Not Too Fast, Not Too Slow 76 5. Lactic Acid Acquitted 98 6. Catch an Edge 120 7. Your Brain on Exercise 145 8. Live High 168 9. Run Like a Woman 189 10. Drinking Games 209 11. More Gain, Less Pain 232 12. Chasing the Holy Grail 252 Epilogue: The Next Race 272 Appendix: Visualizing Protein Structures 277 Notes 281 Glossary 323 Ac know ledg ments 335 Index 337 The Hidden Mechanics of Exercise Prologue Molecules in Motion At a local park on a warm summer evening, a teenager nails a three- pointer while her parents complete a long run. A skateboarder grinds across a rail while his grandmother crushes a backhand down the line. A shortstop nabs a line drive while her brother drills a penalty kick into the lower corner. These routine athletic movements demand power, coordination, and control. If we carefully watch athletes— even amateurs at the gym or on the playing fi elds— we see synchronized limbs, balanced bodies, and precise timing. We also observe occasional moments of clumsi- ness and frustration, highlighting the diffi culty of everyday ath- letic moves. But no matter how diligently we observe, the molecules that motivate these athletic actions remain hidden. We don’t see ions whizzing across membranes, motor proteins tugging on molecu- lar fi laments, or enzymes extracting energy from food. We don’t see receptors morph, carrying signals into cells. We don’t see pro- teins pirouette, converting glucose into muscle power. We don’t see the sifting of sensory information, the decision- making pro cess, 2 the hidden mechanics of exercise the regulation of contractions, or the allocation of energy to meet demand. Today’s physiologists, on the other hand, are fast unveiling the concealed inner workings of the athletic body. We now study exercise not just at the whole body or organ system levels, but also at the cellular and molecular levels. We know that harmo- nized movements of myriad tiny molecules parallel the visible grace of athletes. The connection between this molecular ballet and athletic per for mance is the subject of this book. Modern biology textbooks portray molecules in striking detail. Their illustrations are not vague cartoons of what the molecules might look like, but accurate portrayals of the miniscule structures that compose our bodies. Unlocking the form of biomolecules re- quires extraordinary technical prowess, so textbook images of mol- ecules depict remarkable scientifi c achievements. Yet the fl at, static renderings in textbooks do little justice to the grandeur of biologi- cal molecules in the same way that photographs fail to capture the magnifi cence of a soaring, two-handed, reverse slam dunk. Bio- molecules are not passive entities bumping around in our bodies. Rather, they are active, kinetic, dynamic shape- shifters, morphing into diff erent conformations in the course of their duties. The well- timed muscular contractions of a slam dunk, for example, rely upon the synchronized contortions of countless molecules. In other words, molecules in motion power bodies in motion. Consider hemoglobin, one of the best-studied proteins. On the page, hemoglobin’s structure— four blobs, each cradling an iron atom—is rather uninspiring. But set hemoglobin awhirl in human blood, and its splendor surfaces. Hemoglobin pulsates, relaxing and tensing as it binds and releases oxygen. And it jiggles, subtly Prologue 3 morphing in response to acidity, carbon dioxide concentration, and other factors. Yet we will miss hemoglobin’s full glory if we study it in an inactive human, just as the constraints of city streets mask a sports car’s potential. In Chapter 8, we will see that hemo- globin’s most marvelous behavior occurs during exercise. Two strands of my life meet in this book: my career as a scien- tist and my passion for distance running. My scientifi c background includes training in both exercise physiology and molecular biol- ogy. My running résumé lists over two dozen marathons and a handful of ultramarathons. A recent race experience illustrates how the connections between science and exercise have enriched my own athletic pursuits and explains what I hope readers will gain from this book. The fourth time I attempted the Mohican 100-mile trail run, I stood confi dently on the starting line. My prior outings had been unimpressive. Twice I dropped out well before the fi nish; once I straggled across the fi nish line dragging an injured leg. But in the year preceding my fourth attempt, I systematically addressed the failings of previous years. Sleepiness had been a problem, espe- cially in the nighttime portion of the race, so I planned to start drinking caff einated beverages in the late afternoon. Soreness of my iliotibial band (ITB)— a thin muscle that runs from hip to knee—had often plagued me, so in the months leading up to the race I stretched and strengthened that muscle. Just in case, I wore a tight strap above my knee to relieve strain on the ITB. And fi - nally, dehydration and heat stress had slowed me in past tries, so I carried a water bottle in each hand and two types of salt tablets in my pockets. (Chapter 10, which discusses sports beverages, de- scribes my rationale for taking salt during the race.) 4 the hidden mechanics of exercise My solutions to each of these problems came partly from the advice of other runners and partly from my own experiments on the trails, but also from my knowledge of exercise science. Ath- letes can certainly learn from their own experiences and those of others, but these experiences must be applied cautiously to new situations. We all have diff erent bodies, so what worked for some may not work for others. And conditions diff er from one event to another, so what worked yesterday may not work today. Know- ing how our bodies function can help us apply previous experi- ences to the current situation. This book’s goal—connecting molecules to motion— off ers practical rewards because the body’s molecules hold answers to questions that athletes routinely ask. Should I take salt tablets? Why does exercise make me feel good? Do I need another recov- ery day? What should I eat before the race? The answers hinge on our molecular makeup. Of course, many athletes get along just fi ne without knowing about biomolecules in the same way that many drivers get along without knowing how a transmission works. On the other hand, you can be sure that NASCAR racers know the diff erence between a carburetor and a crankshaft. Like- wise, if you want to maximize your athletic success, it helps to know something about molecular mechanisms. Let’s consider the protein myosin, the work horse of muscle cells. Myosin has a thin tail separated from a globular head by a small fl exible neck. During muscle contraction, myosin heads bind energy- rich adenosine triphosphate (ATP) molecules, break them apart, and capture the released energy. This energy moves the heads, activating them like stretched springs. The energized heads grab other muscle proteins and snap back to their original posi- tion, generating muscular power. So myosin— like hemoglobin— Prologue 5 morphs. Myosin’s contortionist skills, as we will see in Chapter 4, hold the key to practical questions such as “How heavy should a baseball bat be?” Though athletes will fi nd this book useful, it is not a training guide, lifestyle manual, or diet manifesto. The point is not to tell you what to do, but to equip you to seek your own answers. In the language of a legal disclaimer: no part of this book should be construed as health or training advice. On the other hand, the book will help you interpret reports about health and fi tness in the pop ular media, ask good questions of health care professionals and coaches, and make your own well-informed decisions. I have a second, less utilitarian, aim for this book: I want read- ers to marvel with me at the magnifi cence of our molecules in motion. In other words, I seek to convey the stunning beauty and astonishing complexity of our molecular systems, not simply their practical applications. This approach mirrors my rationale for running. I certainly run for the practical benefi ts— fi tness, weight control, stress relief. But I also appreciate the intangible joys of running, as the following continuation of the story about my fourth Mohican 100 illustrates. More than twenty hours after leaving the starting line, long before the fi rst trace of dawn, I walked briskly with a friend, our headlamps illuminating only tiny fragments of the dense sur- rounding forest. In a clearing, we switched off the lights, felt the darkness embrace us, then looked up and watched a shooting star fl ash across the sky.