Table of contents Page number content 1 Table of content 2 Introduction 3 Source of energy for different types of exercise duration and intensity 5 The high-energy phosphate system 6 Anaerobic glycolytic system 6 Aerobic oxidative system 7 The lactic acid system 7 Energy investment phase 8 Energy generation phase 11 Oxygen consumption during exercise 12 Oxygen deficit 13 Why knowing oxygen consumption is important 14 At what exercise level does the body switch to anaerobic energy metabolism? 16 Conclusion 17 References 1 Introduction There is no doubt that exercise physiology is an important field of science that combines between biochemistry, anatomy and physiology. The medical research reached great achievements in this field. In this topic we will pick a very important section in exercise physiology which is exercise metabolism. Exercise metabolism is essential not just for physiotherapists but also for nutrition experts, trainers whether in a club or a gym, and many other professions. In this topic we will mention some points about exercise metabolism. We will start with describing the most important three metabolic pathways that supply our bodies with energy, which are the high-energy phosphate system, anaerobic glycolytic system and aerobic oxidative system. So, we will show how our bodies choose the suitable pathway according to the type of exercise duration and intensity. Then we will move to talk about one system of these systems in detail, which is anaerobic glycolytic system, known as the lactic acid system. After that, we will follow oxygen uptake in our bodies during performing exercise and mention the importance of it. Finally, we will mention how our bodies get energy during intense exercise after energy requirements exceeds maximal oxygen uptake. 2 1- Source of energy for different types of exercise duration and intensity. Before discussing this topic we should mention the contribution of every nutrient substrate. Firstly, Proteins have the minor role in this process, as they contribute to only 2% of the nutrient substrate utilized during exercise and this is for one hour’s duration. This role slightly increases during prolonged exercise for three to five hours duration. During this type, the total contribution of proteins reaches 5-10%. This is very helpful when the other sources of energy have been depleted from our bodies.(Yamany et al, 2019-2020) Secondly, Fats and carbohydrates are the primary sources of energy during exercise. The energy stored in fats and carbohydrates is released when these substrates are broken down. This energy is in the form of ATP. ATP is then used by cells for many purposes, including muscle contraction during exercise. Although each gram of fat stores 9 kcal, while each gram of carbohydrates stores 4 kcal, the rate at which ATP can be formed is higher for carbohydrates than for fats. (Thompson, 2009) Choosing between them is dependent on several factors: • Diet: High-fat and low-carbohydrate diet increase the rate of fat metabolism. • The intensity: Low-intensity exercise relies mainly on fat as an energy source, while high-intensity exercise relies primarily on carbohydrate as an energy source. 3 • Duration of exercise: Long-term, low-intensity exercise has a progressive increase in the amount of fat oxidized by muscles. (Yamany et al, 20192020) Now we will mention an abstract about a very critical molecule in our topic which is adenosine triphosphate. ATP is broken down in a process termed ATP turnover. Water hydrolyzes the unstable chemical bonds of the phosphate groups of the ATP molecule, so the output is an inorganic phosphate molecule (Pi) and adenosine diphosphate molecule (ADP). The released energy is about 9-10 kilocalories (kcal) per mole of ATP. When we start performing work, our bodies need continuous supply of large amounts of ATP, but the initial ATP in our muscles is depleted rapidly. Thus, we need to reform ATP. ATP can be regenerated by the combination of Pi and ADP. This is done through a metabolic process called ATP resynthesis: 1-ADP+ Pi + energy = ATP It can also be regenerated through the combination of phosphocreatine and ADP and this reaction is very fast: 2-PCr + ADP + Energy = ATP + Cr Now let us mention the three energy sources in our bodies: 1) The high-energy phosphagen system 2) The anaerobic glycolytic system 3) The aerobic oxidative system These sources of energy for muscular contraction and other types of work are divided into aerobic and anaerobic, according to whether they need oxygen to provide energy. The high-energy phosphate and the anaerobic 4 glycolytic systems do not require oxygen, while the aerobic oxidative system depends on oxygen to produce energy.) Wells, Selvadurai & Tein, 2009) The regeneration of ATP requires energy. This energy is supplied by the breakdown of complex food molecules, mainly carbohydrates and fats in metabolic energy systems of our bodies. (Wells et al, 2009) Now let us discuss each source of them and the type of exercise supplied by each one of them. 1-The high-energy phosphate system: It is also known as phosphagen system or anaerobic alactic system. This system can be the main energetic system supplying the muscles in the initial 1-15 seconds of high-intensity exercise. The substrates of this system are the adenosine triphosphate (ATP) and phosphocreatine (PCr). On the onset of the exercise, ATP is broken down by the enzyme ATPase, and PCr is broken down by the enzyme creatine kinase to supply Inorganic phosphate for the process of ATP resynthesis as mentioned in the equations (1 and 2) before. (Wells et al, 2009) This system is able to produce large amounts of energy in short duration (from 2.4 mmol/kg/s in sedentary people to 10-15 mmol/kg/s in athletes). The total muscles stores of ATP (3.5-7.5 mmol/kg) and and PCr (16-28 mmol/kg) are very small and consumed quickly during high-intensity exercise. Thus, the ability of an individual to do short-term, high-intensity exercise is dependent on the initial concentrations of high-energy phosphates. (Wells et al, 2009) This system is sufficient in short-term intense events such as weight lifting, 100-meter run or 25-meter swim. These high power output events need high 5 rate of power production in short intervals. If individuals are to perform activities lasting more than 15 seconds, the PCr stores are depleted and ATP resynthesis must take place through other pathways at a lower power output. (Wells et al, 2009) 2-Anaerobic glycolytic system: Our bodies depend primarily on this system as a source of energy to perform high-intensity exercise greater than 12-15 seconds and less than 3 minutes. This system is used mainly in sports events such as 800-meter swim, 1500-meter speed skating and single sprints during football or hockey games. Energy production in this system is done via glycolysis in the cytoplasm of skeletal muscles by the catabolism of carbohydrates in the form of blood glucose or glycogen to pyruvic acid which may be converted into lactic acid through 10 separate but linked steps of chemical reactions (these steps will be mentioned in detail in the following section). (Wells et al, 2009) 3-Aerobic oxidative system: This system is the primarily supplier of a broad range of activities, so it is a very important system in our bodies. It is the energy source of the exercise performed at an intensity lower than the anaerobic threshold (will be mentioned in detail in the last section). As the duration of intense exercise increases, the contribution of this system to the total energy production increases. This system is predominant in prolonged exercise provided that: 1-There is sufficient number of mitochondria in the working muscles to meet energy requirements. 2-Sufficient amount of oxygen is delivered to the mitochondria 6 3-There is no enzymes or intermediates limit the rate of energy production by the Krebs cycle or electron transport chain (the bioenergetics pathways that are responsible for production of ATP in the mitochondria). (Wells et al, 2009) 2-The lactic acid system It is also known as anaerobic glycolysis and it happens in the cytoplasm of eukaryotic cells. Anaerobic glycolysis is the process of taking carbohydrate in the body and putting it through a series of chemical reactions to release adequate energy to rephosphorylate ADP and reform ATP. The final product of this series of chemical reactions is often lactic acid, so this energy system is often called the lactic acid system. Lactic acid is a weak acid which is rapidly dissociated under normal conditions in the body, separating into lactate and a hydrogen ion (H+). (Doyle and Dunford, 2011) Carbohydrates consumed are converted to and used as glucose, or are stored as glycogen within the muscle and liver for later use. Glycogen is a large molecule formed of lots of smaller molecules of glucose. Glycolysis is the breakdown of glucose through a selected series of chemical steps to rephosphorylate ADP and reform ATP. When the substrate is glycogen, the method is named glycogenolysis. (Doyle and Dunford, 2011) The reactions of anaerobic glycolysis can be considered as two distinct phases: 1- An energy investment phase In this phase, there are 2 phosphates added to glucose. Glycolysis begins with hexokinase phosphorylating glucose into glucose-6 phosphate (G6P). 7 This is often the primary transfer of a phosphate group and where the primary ATP is used (this step is an irreversible step). This phosphorylation save the glucose molecule within the cell as it cannot cross the cell membrane. From there, phosphoglucose isomerase isomerizes G6P into fructose 6-phosphate (F6P). After that, the second phosphate is added by phosphofructokinase (PFK-1). PFK-1 uses the second ATP to phosphorylate the F6P into fructose 1,6-bisphosphate (This step is irreversible and for that it is the rate-limiting step). Within the following step, fructose 1,6bisphosphate is lysed into 2. Fructose-bisphosphate aldolase lyses it into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). Dihydroxyacetone phosphate is converted into G3P by triosephosphate isomerase. DHAP and (G3P) are in eqilibrium with one another. (Chaudhry & Varacallo, 2019) 2-An energy generation phase It is important to know that in this phase there are a total of 2-3 carbon sugars for every one glucose molecule in the beginning. The enzyme, glyceraldehyde-3-phosphate dehydrogenase metabolizes the G3P into 1,3diphosphoglycerate by reducing NAD+ into NADH. Then, the 1,3diphosphoglycerate loses a phosphate group by the method of phosphoglycerate kinase to make 3-phosphoglycerate and makes an ATP through substrate level phosphorylation. At this point, there are two ATP created, one from each 3-carbon molecule. The 3-phosphoglycerate is converted into 2-phosphoglycerate by the action of phosphoglycerate mutase, and then enolase converts the 2-phosphoglycerate into phosphoenolpyruvate (PEP). In the final step, pyruvate kinase converts phsphoenolpyruvate into pyruvate and phosphorylates ADP into ATP 8 through substrate-level phosphorylation, therefore making two more ATP (This step is irreversible). So we can say that, the input for one glucose molecule is two ATP, and the output is four ATP (net gain=two ATP) and two NADH and two pyruvate molecules. (Chaudhry & Varacallo, 2019) It is also important to mention that, the net gain glycolysis when glycogen is the substrate is three ATP, as glycogen does not require phosphorylation by ATP, but is phosphorylated by inorganic phosphate (Pi) instead. (Yamany et al, 2019-2020) After that hydrogen ions (H+) are removed frequently from nutrient substrates and carried by two biologically important carrier molecules .The first one is nicotinamide adenine dinucleotide (NAD), the second is flavin adenine dinucleotide (FAD). (Yamany et al, 2019-2020) Both of NAD and FAD carry hydrogen ions and their associated electrons to generate ATP through aerobic glycolysis lately by Kreps cycle and electron transport chain in the mitochondria. If the process is to continue, it is critical that adequate amounts of NAD must be available to accept free hydrogen ions from glyceraldehyde 3phosphate and there is two methods that the cell follows to restore NAD from NADH: 1-First, if there is sufficient amount of oxygen, the hydrogen ions from NADH can be transported to mitochondria of the cell and contributes to aerobic production of ATP. 2-Second, if oxygen is not available or the cell lacks mitochondria; pyruvic acid can accept the ions and form lactic acid. This reaction is catalyzed by lactate dehydrogenase enzyme (LDH) with end result of formation of lactic 9 acid and reformation of NAD. It is obvious that recycling of NAD is the reason of accumulation of lactic acid during exercise. (Yamany et al, 20192020) As a conclusion to this we can say that the microenvironment of the cell determines what will happen to the pyruvate following the steps of the glycolysis. If there is no oxygen available, there are no mitochondria in the cell, or energy demand has rapidly increased to be above the rate at which oxidative phosphorylation can provide adequate ATP, pyruvate can be converted to lactic acid by the enzyme lactate dehydrogenase. This step includes the oxidation of NADH to NAD+, allowing glycolysis to continue through the glyceraldehyde-3-phosphate dehydrogenase reaction as mentioned before. (Melkonian & Schury, 2019) (Figure I) 10 3-Oxygen consumption during exercise It is also called Oxygen uptake (VO2), it is the amount of oxygen taken in and used by the body per minute to produce massive amounts of ATP to the muscle cells via aerobic oxidative system. Although there are processes that can produce ATP without oxygen (O2), these anaerobic systems (The lactic acid system and high-energy phosphate system) are limited in their capacity to produce adequate amounts of ATP. (Thompson, 2010) The importance of oxygen is that it is the last receptor in the electron transport chain, so the availability of oxygen in the muscle cells is critical to continue the process of aerobically generating massive amounts of ATP (32 ATP per glucose molecule and 33 ATP if the substrate is glycogen as mentioned before) to continue the process of generating force. (Yamany et al, 2019-2020) Now let us talk about the pathway of consuming oxygen during exercise: The pathway for oxygen transport includes three main structures; the lungs, the circulation, and the muscle. Oxygen follows a linear pathway without branches. Respiration is a regulated process in line with the demands of aerobic metabolism: as muscle demands for ATP increases, oxygen demand is increased proportionally. Increases in oxygen transport that occur during exercise are considered as a result of: 1-Increase in ventilation and uptake of oxygen into the blood. 2-Increase in cardiac output and the transport of oxygen by the blood. 3-An increased extraction of oxygen by the muscles due to increased oxygen metabolism in the mitochondria. 11 Respiration is a limited function, and the limit of the maximal rate of oxygen uptake is termed VO2 max. Any additional energy requirements above that intensity will be fulfilled by the anaerobic glycolytic system. Surely, VO2 max is higher in athletes than nonathletes, and to a certain extent it can be elevated by training. (Wells et al, 2009) The rate of oxygen use (VO2) is sometimes expressed in liters of O2 per minute (liters per minute) or it can be expressed as a function of body weight, as milliliters of O2 per kilogram of body weight per minute (milliliters per kilogram per minute). Expressing VO2 as a function of body weight is important when comparing the different sizes of people during exercises such as running. (Thompson, 2010) When we start the exercise our bodies take one or two minutes to reach the steady state (the steady state refers to the plateau in oxygen uptake that is reached following a few minutes of exercise) so there is lag in oxygen uptake at the beginning of exercise and this lag is termed oxygen deficit. Definition of Oxygen Deficit: “the difference between oxygen intake by the body during early stages of exercise and an equal time period after steady state has been reached.” (Yamany et al, 2019-2020) As shown in (Figure II), Oxygen deficit is represented as the shaded area on the left. Surely the duration of oxygen deficit in trained subjects is shorter than untrained subjects, as trained subjects reach steady state of VO2 fast. This is because trained subjects have better-developed aerobic bioenergetic capacity, resulting from either cardiovascular or muscular adaptations induced by endurance training as shown in (Figure III). (Yamany et al, 2019-2020) 12 (Figure II) (Figure III) Why knowing oxygen consumption (VO2) is important? VO2 shows energy expenditure, meaning that measuring VO2 provides an estimate of calories burned. Approximately 5 kcal of energy are expended 13 for every liter of O2 consumed. Thus, a person with a VO2 of 1 L/min is burning 5 kcal each minute. As one exercises harder, VO2 rises, meaning that energy expenditure is higher. The relationship between the type and intensity of activity, O2 consumed, and energy used allows researchers to estimate the caloric expenditure for different tasks. This information can be used to shape exercise plans to make appropriate programs of weight control goals. (Thompson, 2010) 4-At what exercise level does the body switch to anaerobic energy metabolism? We mentioned in the last section that any energy requirements above VO 2 max is fulfilled by the anaerobic glycolytic system, now let us explain this in more detail. The exercise intensity at which lactic acid starts to accumulate in the blood and muscles has been termed anaerobic threshold. Anaerobic threshold is the point during exercise when the individual starts to feel discomfort and the burning sensation in his muscles. It can be identified during clinical incremental exercise tests as it is the point when carbon dioxide production (VCO2) exceeds oxygen uptake (VO2). In exercise physiology lactic acid accumulation is a measured variable and its typical values range from 2 mmol/L at rest to 4 mmol/L in moderate exercise to 16 mmol/L during maximal anaerobic exercise (2-minutes maximal sprint). Lactic acid is removed from type II muscle fibers (fast glycolytic fibers), where it is primarily to produced, to type I (oxidative fibers) where it is oxidized in mitochondria allowing individuals to continue training for longer periods. But when the energy requirements exceeds maximal oxygen uptake, the body will make a transition from aerobic to anaerobic metabolism to supply the body during intense exercise. Thus, high amounts of lactic acid 14 will accumulate within our blood and muscle fatigue takes place to oblige us to stop exercising. (Wells et al, 2009) 15 Conclusion Finally, we can conclude that our bodies supply us with different sources of energy during our daily activities and exercises accurately, according to the level of intensity and duration. And we saw that however the lactic acid system is a very useful system in short-duration, high-intensity exercises as it is takes short time, using it in high rates can make us suffer from metabolic acidity. Then, we knew the importance of oxygen during exercise and how it is used. Then, we highlighted an important point that in very high intensities of exercise, our bodies shift from aerobic to anaerobic metabolism. So, anaerobic metabolism is important as it can fill the gaps of the aerobic system (oxygen deficit and production of ATP is less than required during intense exercises). 16 References Chaudhry, R., & Varacallo, M. (2019). Biochemistry, Glycolysis. In StatPearls [Internet]. StatPearls Publishing. Dunford, M., & Doyle, J. A. (2011). Nutrition for sport and exercise. Cengage Learning. Hassan, A.I.,Yamany, A.M., Shehata,S., Abutaleb,E. and El-Sayyad,M.(20192020). Principles of exercise physiology. Cairo-Egypt:Al-Resala press. Melkonian, E. A., & Schury, M. P. (2019). Biochemistry, Anaerobic Glycolysis. In StatPearls [Internet]. StatPearls Publishing. Thompson, D. L. (2009). Fitness Focus Copy-and-Share: The Crossover Concept. ACSM's Health & Fitness Journal, 13(1), 4. Thompson, D. L. (2010). Fitness Focus Copy-and-Share: What is Oxygen Consumption?. ACSM's Health & Fitness Journal, 14(1), 4. Wells, G. D., Selvadurai, H., & Tein, I. (2009). Bioenergetic provision of energy for muscular activity. Paediatric Respiratory Reviews, 10(3), 83–90. doi:10.1016/j.prrv.2009.04.005 17