Usain St. Leo Bolt, World Champion
Usain St. Leo Bolt (See Figure 1), a Jamaican sprinter who competed in the 2012 London Olympics, is widely known as the fastest man ever. Bolt is the first man in history to hold both the world records for the 100 meter and 200 meter sprint. He earned gold medals in both of these events at the 2008 and 2012 Olympics (Usain Bolt 2012). When sprinting, Bolt’s body must produce enough energy to run 100 meters in 9.63 seconds. There are amazing processes going on simultaneously within this runner’s body that are allowing this all to happen.
Aerobic and Anaerobic Respiration
To understand what is going on in an athlete’s body, we must first understand the difference between aerobic respiration and anaerobic respiration. When an athlete runs, there is a high demand for oxygen and a limited supply. A Sprinter like Bolt finishes a race before he is able to breathe heavier and accrue more oxygen. For the most part, Bolt’s body is running on a process called anaerobic glycolysis (Kudo et al. 1996). Anaerobic essentially means “without oxygen.” Anaerobic glycolysis allows his body to produce limited energy when he has low levels of oxygen in his system. Every time Bolt takes a breath, his body is supplied with a very limited amount of oxygen that is instantly used to fuel a process that yields much more energy: aerobic glycolysis coupled to the citric acid cycle (also known as Kreb’s cycle or the tricarboxylic acid cycle) by acetyl coenzyme A (Acetyl CoA). Acetyl-CoA is produced when the oxygen supply in our body is abundant. This is one of the reasons we breathe more heavily when we engage in physical activity. Our body has feedback mechanisms that tell us to breathe in more oxygen to allow our body to produce energy at a faster pace (Skou 1965, Lamb and Stephenson 2006b).
The Origin of Energy
Metabolic processes begin long before an athlete competes. In fact, the precursors to these processes begin at the dinner table. Energy begins in the form of a healthy meal consisting of carbohydrates, fatty acids, and amino acids. These “fuel” molecules are metabolized into substances such as glucose, pyruvate, lactate, and the aforementioned acetyl CoA.
The end product of these metabolic processes is a very important molecule called adenosine triphosphate (ATP). ATP is the molecule that supplies our body with the necessary energy to perform. The cells that make up our body all use ATP to perform many necessary functions such as cell signaling (Bell et al. 2003), transport of molecules in and out of cells (Winder and Hardie 1996), muscle contraction (Adelstein and Eisenberg 1980), and metabolism (Skou 1965, Lamb and Stephenson 2006b). Through cell signaling, ATP allows our central and peripheral nervous system to function properly (Bell et al. 2003). It allows actin and myosin crossbridges in our muscles to function so that we can flex and contract muscles (Adelstein and Eisenberg 1980), allowing us to move and perform. In metabolism, ATP allows glycolysis to continue, which in turn produces more ATP (Skou 1965, Lamb and Stephenson 2006b). ATP is one of the most important molecules in our body because essentially, it gives the cells in our body the ability to perform all the functions necessary to sustain life. Studies have shown that a decrease in ATP is the chief factor responsible for increased energy production.5 When our body has low levels of ATP, it knows when to produce more and will increase the rate of glycolysis and the citric acid cycle accordingly.
Glycolysis literally translated means to split sugar (Glucose—sugar, lyse—to split). Virtually all sugars (whether arising from our diet or from catabolic reactions in the body) ultimately can be converted to glucose; glucose is free to diffuse in and out of the cells that make up the different tissues of our body. Diffusion generally occurs from areas of high concentration to areas of low concentration. For this reason, when cells are depleted of glucose, more is able to be supplied through diffusion.
Glycolysis can be aerobic when we have sufficient oxygen, or anaerobic when the oxygen in our system is low. The reactions involved with glycolysis begin in the same pathway, regardless of the amount of oxygen present.
Glycolysis (See Figure 2) begins when a phosphorous molecule is added to the glucose molecule to form glucose 6-phosphate. This process is called phosphorylation and in this case, the phosphorylation is performed by an enzyme called hexokinase. Enzymes are biocatalysts that speed up reactions such as this one. The phosphorylation is irreversible. Once the phosphorylation occurs, the glucose molecule is blocked from leaving the cell without some kind of special carrier molecule. This commits the glucose molecule to the glycolysis process. The phosphorylation of glucose uses the phosphorous from an ATP molecule, which almost seems counterproductive since ATP is what glycolysis is trying to produce, but we can consider this an investment since more ATP will be produced further along in the process. When the ATP gives up a phosphorus molecule, it is converted to adenosine diphosphate (ADP).
Next, the enzyme phosphoglucose isomerase converts glucose 6-phosphate to fructose 6-phosphate. Fructose 6-phosphate is an isomer of glucose 6-phosphate, which means that they have the same chemical formula (i.e. they are made of the same number and type of atoms) but a different structural formula. This means that they are made up of the same atoms, but they are shaped differently. After isomerization, phosphofructokinase (an enzyme) phosphorylates fructose 6-phosphate to form fructose 1,6-bisphophate. An additional investment of ATP is made in the phosphorylation of fructose 6-phosphate. This makes two total ATP molecules invested into glycolysis for each molecule of glucose. Soon we will see why glycolysis is worth the investment of energy in the “payoff” phase.
Once fructose 1,6-bisphophate is made, it is cleaved (or split) into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate by the enzyme Aldolase. This is the ‘lysis or lyse’ step in glycolysis. Dihydroxyacetone phosphate is a precursor molecule only and cannot proceed further down the pathway of glycolysis without modification. Triose phosphate isomerase (an enzyme) catalyzes the reversible conversion of dihydroxyacetone phosphate to another molecule of glyceraldehyde 3-phosphate. This increases the total number of glyeraldehyde 3-phosphate molecules to two per molecule of glucose metabolized.
The glyceraldehyde 3-phosphate molecules are oxidized to 1,3-diphosphoglycerate by glyceraldehyde 3-phosphate dehydrogenase (an enzyme). This is an oxidation-reduction reaction converting nicotinamide adenine dinucleotide (NAD+) to a reduced form (NADH) and phosphorylating each of the glyceraldehyde 3-phosphate molecules to form 1,3-diphosphoglycerate (Skou 1965, Lamb and Stephenson 2006b). Glycolysis is closely regulated by the amount of NAD+ to NADH in our system (Witters et al. 1994). You can imagine that if there is a large buildup of NADH and not much NAD+ available, this step will slow down the rate of glycolysis.
Each 1,3-diphosphoglycerate is used to form an ATP using the enzyme Phosphoglycerate kinase and an ADP molecule (remember that two ADP were created in the investment of ATP in the earlier stages of glycolysis). This forms two ATP molecules so that the net production of ATP is now zero per molecule of glucose. 3-phosphoglycerate is the resulting molecule from each 1,3-diphosphoglycerate.
Next, the phosphate atom is shifted on the #3 carbon of 3-phosphoglycerate to #2 carbon by phosphoglyceromutase to form 2-phosphoglycerate. 2-phopshoglycerate is then dehydrated by the enzyme enolase to form phosphoenolpyruvate (PEP). The next reaction forms the molecule pyruvate. Pyruvate is formed by the enzyme pyruvate kinase producing an additional ATP molecule from each PEP molecule. Two ATP molecules are formed for each glucose molecule. This gives a net of two ATP molecules for each molecule of glucose metabolized. The resulting pyruvate molecule is where anaerobic glycolysis and aerobic glycolysis differ (Skou 1965, Lamb and Stephenson 2006b).
Sprinting, lifting weights, and short bursts of energy within aerobic exercise are all fueled by anaerobic respiration. When Bolt is sprinting, his oxygen demand exceeds the supply. Anaerobic glycolysis is the way our metabolism supplements the energy demand for these short, intense bursts of activity. Events lasting approximately 10 seconds or somewhat longer (e.g. 100-m run) utilize anaerobic glycolysis for energy in ATP production (Kudo et al. 1996).
Remember, the NADH that was formed in the oxidation-reduction reaction in glycolysis. When oxygen levels are low, this NADH reacts with the pyruvate leftover from glycolysis to form lactate and NAD+. This NAD+ is then recycled and used to allow the glyceraldehyde 3-phosphate molecules to be oxidized to 1,3-diphosphoglycerate in glycolysis allowing the glycolysis cycle to continue to produce more ATP (Skou 1965, Lamb and Stephenson 2006b). This can only be sustained for short periods of time (Kudo et al. 1996). Once our body adjusts to the strenuous activity and the energy demand by breathing in oxygen, aerobic glycolysis kicks in.
It is interesting to know that production of lactate and other metabolites during extreme exertion results in the burning sensation that is felt in active muscles. While lactic acid accumulation inside muscle fibers is responsible for the burning sensation we feel, it is not responsible for decreased muscle performance (“muscle fatigue”). There are several broad types of muscle fatigue, and the contribution of each to the overall decline in performance depends on the muscle fiber type and the intensity and duration of the activity (Tilton et al. 1991). Arguments have been made that lactic acid buildup in active muscles is advantageous and other arguments have countered saying that it is disadvantageous (Witters et al. 1994). Those that advocate that lactate is advantageous make the argument that the lower intracellular pH, due to the acidity of lactate, counters the effects of high potassium levels which inhibit membrane transport channels from functioning at full capacity (Tilton et al. 1991). Those that argue that lactate has an inhibitory effect report that lactate induced an impairment of calcium release channels (Bangsbo and Juel 2006). Calcium plays a crucial role in muscle contraction (Kudo et al. 1995), so this argument makes a valid point as well.
Aerobic Glycolysis and Acetyl CoA
For longer distance running, when oxygen supply is able to meet the demand, oxidative decarboxylation of pyruvate occurs to form Acetyl CoA yielding an NADH for each pyruvate. This occurs in cells that contain mitochondria. The mitochondria are considered “the powerhouses of the cell” because they are where the citric acid cycle occurs. Oxidative decarboxylation of pyruvate by the enzyme pyruvate dehydrogenase converts pyruvate (inside the mitochondrial matrix) to acetyl CoA.
Acetyl CoA is the precursor to the citric acid cycle (Skou 1965, Lamb and Stephenson 2006b).
The Citric Acid Cycle
The citric acid cycle is an eight-step process after pyruvate has been converted to acetyl CoA (See Figure 3). It begins by the condensation of acetyl CoA and oxaloacetate to form citrate by the enzyme citrate synthase. Next is the isomerization of citrate to isocitrate, a molecule with the same number of atoms, with a different makeup. After isomerization, oxidation and decarboxylation of the resulting isocitrate occurs. This converts isocitrate to alpha-ketoglutarate and is catalyzed by the enzyme isocitrate dehydrogenase. This is another oxidation-reduction reaction and requires an NAD+ molecule. This forms the first of three NADH molecules.
This reaction is followed by another oxidation-reduction reaction. Oxidative decarboxylation of alpha-ketoglutarate to form succinyl CoA by alpha-ketoglutarate dehydrogenase complex occurs. This forms another NADH from NAD+. Succinate kinase catalyzes the cleavage of succinyl CoA to form succinate. The cleavage of succinyl CoA produces a guanosine triphosphate (GTP), which contains the same energy content as an ATP molecule. After succinate is formed, it is oxidized, in another oxidation-reduction reaction, to form fumarate. Since the reducing power of succinate is not sufficient to reduce NAD+ to NADH, the oxidation-reduction reaction is enabled this time by the molecule flavin adenine dinucleotide (FAD). This forms the reduced form of FAD, FADH2. Fumarate is then hydrated to the molecule malate by the enzyme fumarase.
The final step of the citric acid cycle is the oxidation of malate to oxaloacetate catalyzed by the enzyme malate dehydrogenase. This produces the third and final NADH molecule and leaves an oxaloacetate molecule to react with acetyl CoA to renew the cycle. Keep in mind that for each glucose molecule, two molecules of acetyl CoA are formed. This produces a total of six NADH molecules, two FADH2 molecules, and two GTP molecules for each glucose molecule. If we add all of the energy yielding products of the breakdown of one glucose molecule, we have a total of ten NADH molecules, two FADH2 molecules, two GTP molecules, and a net of four ATP molecules. Each NADH is capable of producing 3 ATP, each FADH2 is capable of producing 2 ATP, and each GTP is equivalent to one ATP. This yields a total of 38 ATP assuming that all of these products go on to produce an ATP. We can now see why we need more oxygen when we work hard over longer distances. The oxygen is essential to allow glycolysis to link to the citric acid cycle and produce more energy to sustain us (Skou 1965, Lamb and Stephenson 2006b).
Summary – How does this affect running?
As Bolt lines up at the starting line, he listens for the starting gun. His body has already started to produce extra ATP because of his warm-up exercises. As the gun goes off, ATP begins working in conjunction with actin and myosin fibers that make up his muscles, enabling him to contract his muscles and move. His central and peripheral nervous system communicate with his muscles through cell signaling, which is enabled by ATP. His cells start to notice a lack of ATP, which signals the production of pyruvate through glycolysis. With each breath of air, oxygen molecules diffuse from his lungs into his bloodstream and finally into his cells where they allow oxidative decarboxylation of pyruvate forming acetyl CoA. Acetyl CoA allows the metabolism of oxaloacetate in the citric acid cycle to produce more ATP. As his cells are starved of oxygen between breaths, anaerobic glycolysis occurs and pyruvate is fermented into lactate in his muscles, producing a burning sensation in his muscles. Bolt crosses the finish line well ahead of his competitors, all made possible by the adenosine triphosphate produced during metabolism.
By: Josh Sewell, University of Utah
Joshua Sewell graduated from Brigham Young University-Idaho with a Bachelor’s of Science in chemistry and a minor in biology. He is fascinated by biochemistry and the processes that make the body work. Josh is currently a graduate student working on a Ph.D. in chemical engineering where he is focused on microbially enhanced coalbed methane recovery and applications. Outside of the lab, Josh enjoys spending time with his wife, Sara, and his two daughters, Oakley and Zoe.
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Articles by Josh Sewell.