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Ex Phys Midterm 1

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Kinesiology 2230A/B
Glen Belfry

Exercise Physiology: Metabolism During Exercise (Lecture 1) Course Sections Metabolism: • ATP-PCr system • Anaerobic glycolysis • Aerobic glycolysis • Fat Oxidation • VO₂ and VCO₂ Ventilation: Cardiovascular: • The cardiovascular system is important in the regulation of blood pH • It enables the body to keep the pH at the appropriate levels • This becomes particularly problematic during high-intensity exercise Muscle: • Looking at the mechanism of contraction • Contractions are initiated from not only a neuromuscular prospective, but also for the purpose of exercise (actin-myosin complex) Adaptation: • Adaptation of the various physiological systems • What are the actual changes that are going to occur from the training? A. Energy • There are many different types of energy • Wind can be transformed into electrical energy • Sunlight can be transformed into electrical energy • Nuclear fission involves the collision of different atoms to produce energy • What we’re interested in, is transforming food energy (carbohydrates, fats, etc.) into energy that we can actually use to do work Running : • To be a successful marathon runner you have to be able to generate relatively high energy outputs for a long period of time • Focusing on the musculature, the marathon runner is very thin and relatively short • The 400m runner has a distinctly different body type than the marathon runner; show has to be very fast, and therefore has to be able to produce a lot of power (therefore she has a more profound musculature) • The sprinter has the most distinct musculature (in every area) in order to generate power for a relatively short period of time Energy Production • This is a logarithmic graph that shows the power output over a short period of time • The ATP-PCr system (anaerobic) peaks somewhere around 4-5 seconds, where you can generate the greatest amount of power • The second system (the anaerobic glycolysis/aerobic) peaks somewhere around 10-15 seconds and then drops off very quickly • By the time you’ve reached about 50-60 seconds of maximal exercise, you’re anaerobic systems (ATP-PCr and Anaerobic Glycolytic) have done their work • After this point, by about 100-200 seconds, your aerobic system is giving you all the energy that is requires for the event • There are different body types, different muscles masses, and different abilities to generate power for specifi c durations • The different energy systems are specifi c to the duration and to the power output that is required • Example: running as fast as you can for 15 minutes uses very different amounts of energy that running as fast as you can for 5-6 seconds • Running for 15 minutes will most predominantly use the aerobic energy system (95% of the energy required will come from here) • Running for 5-6 seconds will most predominantly use the ATP-PCr system • We’re talking about maximal exercise for different durations • As the duration of the exercise/length of the event increases the power that you can generate decreases • This is specific to the energy system at specifi c points in time • So, we go from the ATP-PCr system, to the anaerobic glycolytic system, to the aerobic glycolytic system and fi nally to the aerobic breakdown of fats where the power outputs are relatively low What is Energy? • Energy is the potential to do work • Energy in biological reactions produces heat • Hence energy intake and output is measured in either kilocalories (kcals) or joules (1 kcal = 4.184 (4.2) kjoules) • 1 kcal (or 4.2 kjoules) represents the amount of energy necessary to raise the temperature of 1kg of 1L of water 1°C at 15°C • The unites for energy intake/output is generally kcals, joules, or oxygen consumption (the more oxygen we consume, the more energy we’re going to be producing) • The amount of heat that you produce is directly related to the amount of energy that you produce Efficiency • Efficiency is low in humans; 60-70% of the energy in our bodies is released as heat • The chemical reactions occurring in muscle generate heat that is vital for maintaining body temperature • At rest, all metabolic processes result in heat production (37°C); this temperature has to be maintained in order for biological processes to occur optimally • Measuring heat in various phases of muscle contraction indicate the existence of exothermic (releases energy) chemical reactions • So, not only are we trying to produce enough energy to do the work (i.e. exercise) but we also have to maintain this specifi c temperature • Efficiency, therefore, is low because not only are we producing energy to do work, but we’re also producing energy just to keep out body warm Heat Study • This study speaks to the fact that as you do exercise, you’re going to produce heat • The heat that you’re producing is refl ecting the amount of energy that is available • There were 3 different conditions: • 10 seconds of tetanus • ‘Tetanus’ refers to an isometric contraction of the muscle • A certain amount of heat is generated • 30 seconds of tetanus • As the amount of time during which the muscle is contracted is increased, so is the amount of heat being generated (it continues to rise) • 30 second twitches • As opposed to having a full isometric contraction, they were looking at twitched every 5 seconds using electrical stimulation • Every 5 seconds there was a decrease in heat • The point that they were trying to make here, was that when you change that muscle stimulus to an intermittent stimulus, the heat generation occurred at a much slower rate • So, when muscles do work, the amount of heat that is generated is directly related to the actually work that is being done B. Source of Energy • Sunlight is the key source of energy on our planet • There is a nice relationship between us and plants, because we can use the carbohydrates and oxygen that plants produce as waste while they can use the carbon dioxide and water that we produce as waste • CHO = carbohydrates Nutritional Sources • Fats, carbohydrates and proteins • All are composed of carbon, hydrogen and oxygen with the addition of nitrogen in the case of proteins • Different arrangements of C, H and O determine whether it is fat or a carbohydrate • In order to obtain energy from these nutritional sources we need to breakdown and metabolize their components • Proteins only contribute 5-10% of the energy that is required during exercise; therefore, they are not a signifi cant enough factor to focus on • Carbohydrates (CHO) can be stored in the muscle and most readily available C. Body Stores of Fuels and Energy Carbohydrates : • There are relatively small stores of carbohydrates in the body • If we look at the liver, there are only 451 calories of carbohydrates; if we were to undergo an hour of moderate exercise we could burn up to 500 calories • So, after an hour of exercise, your liver glycogen stores would be depleted • Muscles glycogen (the store of carbohydrates within the muscle itself) gives us more calories (some 5 times higher than what is stored in the liver) • Glucose in the body fl uids is also quite small (only 62 calories); within about 10-15 minutes you would deplete the glucose in the bloodstream • The is why Gatorade and PowerAde are important solutions during exercise to help maintain the glucose levels in the bloodstream, so that you can continue to have that carbohydrate source eben if you are enduring an exercise that will last a number of hours in duration Fat: • There is a tremendous amount of calories stored as fat (subcutaneous fat) compared to the amount of energy stored as carbohydrates • There are some fat stores within the muscle itself (intramuscular stores) which are significantly less ‘calorie rich’ than the subcutaneous fat • The greatest storage of energy is in the subcutaneous fat From a Volume Perspective: • If CHO is the most efficient and readily available fuel, why don’t we store more? • 1 cup of Almonds: 549 kcals from carbohydrates, 433 kcals from fat • 1 cup of Shredded Wheat: 82 kcals from carbohydrates, 5 kcals from fat • Evidently, carbohydrates are an ineffi cient way of storing energy from a volume perspective From a Mass Perspective: • The energy yield from 1g of carbohydrates and from 1g of fat: • 4 kcals in 1g of carbohydrates are available • 9 kcals in 1g of fat are available • So, from a mass perspective, there is more than twice the energy in a gram of fat than a gram of carbohydrate • Hydrogen is particularly important in energy production (key in kreb cycle and ETC; when talking about aerobic exercise) Glycogen and Glucose : • Multiple glucose molecules are stored as glycogen • Glycogen is basically just a series of glucose molecules bound together by a water molecule (glycogen is stored with water) • There are much fewer hydrogens available in glucose than in glycogen • Therefore, glycogen is going to give us a lot more energy than the glucose molecule Triglycerides (Fats): • Three fatty acid molecules associated with glycerol make a triglyceride • By looking at all of the hydrogen’s associated with the fatty acids, it is evident that there is a tremendous amount of energy that is available on the breakdown of fats • Since hydrogen’s represent the amount of ATPs generated, than the amount of energy available is going to be much higher D. Kcals/L of O₂ (VO₂) vs. Kcals/g (Mass) • Essentially looking at VO ₂ vs. mass • VO₂ represents the oxygen that is consumed (utilized) • We’re talking about the amount of energy that is derived upon consuming 1L of oxygen vs. the amount of kcals per gram of carbohydrates or fats • The metabolism of a molecule of carbohydrates yields 5.05 kcals/L of O ₂ consumed, yet it only stores 4.1 kcals/g • The metabolism of a molecule of fats yields 4.69 kcals/L of O ₂ consumed and stores 9.4 kcals/g • Therefore, you can consume less oxygen and get more energy (calories) – this is a good thing • As far as being efficient in the usage of oxygen, carbohydrates are much better • As far as looking at the mass (storage) of oxygen, fats are much better • Carbohydrates are stored with water, so for every gram of carbohydrate that is stored, it will be stored with 2.7g of water • If we have 1g of carbohydrates and add 2.7g of water to it, we will end up with a lot less energy per gram of actual carbohydrate • Therefore, we only end up 1ith 1.1 kcals/g stored of glycogen in the body • As far as storing energy in the body as fat, we get 9.4 kcals/g • So, there’s a huge difference • Conclusion : CHO provides about 10% more energy per litre O ₂ but fat stores about 9 times the energy of CHO per gram Ultra-Marathons: • During these ultra-marathons an athletes fat stores become extremely important because they are running for such a long period of time ( • This is because there is no way to eat the number of calories necessary in carbohydrates E. Factors Affecting Energy Production • The primary factors affecting energy production are total energy demand coupled with rate of energy demand • Total energy demand – how much energy is required? • Rate of demand – how fast is the energy required? • Think about someone running for 8-10 seconds; this involves a high-energy output, but only for a short duration, so the total energy demand will be relatively low • However, if someone is running a marathon (ex. 2-5 hours), the total energy demand will be extremely high • So, how does the body meet these energy requirements? • There are three systems that we are going to be looking at (2 anaerobic and 1 aerobic): 1) Anaerobic: • Anaerobic means that you can release energy without having to consume oxygen (i.e. can produce energy in the absence of oxygen) • The two energy systems that fall under the anaerobic category are: • ATP-PCr system • Anaerobic glycolytic system • There is going to be oxygen available in the muscle, but we can still produce energy without actually using this oxygen store 2) Aerobic: • The aerobic system can use both carbohydrates and fats • Oxygen is going to be utilized the aerobic system Metabolic Pathways: • The various energy systems are arranged in metabolic pathways which allow for the release of energy from food in sequential steps or reactions • The number of reactions within the metabolic pathways are going to differ between the different energy systems • The number of reactions is going to dictate how quickly energy is going to be released from that specifi c pathway • The more reactions that are involved in a metabolic pathway, the longer it is going to take for the overall energy release to occur Exercise Physiology: Metabolism During Exercise (Lecture 2) Bioenergetics of Rowing : • There are a number of physiological factors that are important in the sport (ex. stroke rates, fast starts etc.) • The key component from a physiological perspective is the duration • They have to be able to keep up their endurance for anywhere from 5.5-8 minutes • NOTE: the duration is dependent upon the type of people in the boat • This is a predominantly aerobic event • However, there is a significant amount of mass that the rowers must get up to top speed as quickly as possible • Not only is there going to be a very high aerobic component (because of the length of the meet itself and the time it takes to complete the course), but there will also be a large strength component as well (because they have to overcome the inertia of a large mass in order to get up to top speeds) Review (Last Lecture) • The primary factors affecting energy production are total energy demand coupled with rate of demand • When we talk about the power and the peak power, it’s during maximal exercise specific to that duration • With regards to marathon runners (2-5 hours), they’re going to need a tremendous amount of energy, but the rate of energy demand is every low • In contrast, a sprinter would have a small total energy demand, but a high rate of demand (they only need energy for a few seconds, but they need it fast) • There is an inverse relationship between the total energy demand and the rate of demand • When the total energy demand is high, the rate of that demand tends to be very low Review of the Three Energy Systems : • ATP-PCr System • This is our initial energy system • We utilize this system in the fi rst few seconds of maximal exercise • Anaerobic Glycolytic System • This is our second energy system • We utilize this system around 10 seconds or so • Aerobic Energy System • This is our final energy system • We utilize this system after about 100 seconds Review of Sources Of Energy: • All the energy on the planet initially comes from sunlight • As far as plants are concerned, we look at photosynthesis occurring in the chloroplast in the plant • They’re going to be using energy from the sun + carbon dioxide + water to make carbohydrates (glucose) • Carbohydrates are important to us because they are what us broken down obtain food energy (used to do work) • Energy is the key component from the breakdown of carbohydrates • Plants consume the carbon dioxide that we release as waste • Also, we use the oxygen that plants release as waste as part of the aerobic pathway F. Free Energy Change (ΔG) • Refers to the change in energy over a number of reactions that are going to occur in a metabolic pathway • The part of the total energy change in a reaction that is capable of doing work • There are two terms that are particularly important for us to defi ne the different types of energy transfer (release or consumption): • Exergonic Reaction : energy is released in the reaction • Example: the breakdown of ATP to produce energy • The energy change is considered negative because the reaction is losing energy (it is being released) • Endergonic Reaction : energy is consumed in the reaction • Example: the joining of ADP, Pi and energy to form ATP • The change is considered positive because the reaction is gaining energy (consuming it) • NOTE: endergonic reactions can only occur when coupled to exergonic reactions • Using ATP-PCr system as an example • If a PCr molecule is broken down into Pi and Cr we end up with these individual components + energy • This energy from the exergonic reaction of the breakdown of PCr is going to enable the endergonic reaction to proceed (the formation of ATP from ADP, Pi and energy) • Endergonic reactions have to be coupled with exergonic reactions; if they’re going to consume energy, that energy have to come from somewhere Again: • When energy is released ΔG is considered negative and the reaction is exergonic • When energy is added ΔG is considered positive and the reaction is endergonic • Endergonic reactions can only occur when coupled to exergonic reactions Efficiency (Review): • Efficiency is the amount of energy that you’re going to consume to produce relative to the amount of work that you’re able to produce • In other words, the amount of energy required to do a certain amount of work • Greater efficiency means that with the same amount of energy, you can do more work • The efficiency in humans is relatively low • 60-70% of energy used in our bodies is released as heat • The chemical reactions occurring in muscle generate heat that is vital for maintaining body temperature (37°C) • Measuring heat in various phases of muscle contraction indicate the existence of exothermic chemical processes • 37°C is relatively high • This mechanism is like a furnace in the winter; if we wanted to keep our houses that warm, our furnace would have to be running a lot more than if we were to keep it at room temperature • So, to maintain that temperature we require signifi cant amounts of energy; we always have to keep our bodies warm • This differs in reptiles/lizards who don’t produce their own heat; their body temperatures fl uctuate, and this fl uctuation dictates whether they’re going to be active or inactive • From humans’ perspective, we have to generate enough heat to keep our body temperature at 37°C at rest • So, we’re consuming/producing a lot of energy to maintain this body temperature, but we’re not actually doing a lot of work Kcals/L O₂ vs. Kcals/g (Release vs. Storage): • Kcals/L O₂ refers to the amount of energy that’s produced per litre of oxygen consumed • We consume oxygen because it is basically the endpoint of the aerobic metabolic pathway • As we consume oxygen, it’s reflecting the oxygen that we’re producing • What we find is that carbohydrates give more energy per litre of oxygen consumed • 5.05 kcals/L oxygen consumed for CHO vs. 4.69 kcals/L oxygen consumed for fats • So, the substrate is going to affect the respiration rate • If you’re burning fat, you will have to breathe a little more to produce the same amount of work, because it is not quite as effi cient as burning carbohydrates (they have different effi ciencies) • NOTE: there is a difference when talking about the amount of energy stored per gram of carbohydrates vs. actual stored carbohydrates • Glycogen, the storage form of carbohydrate, uses water as a signifi cant portion of the binding between the glucose molecules • If we have 1g of carbohydrates, were really only storing 1.1 kcals/g as glycogen • So, if we think about the amount of energy we store as fat vs. the amount of energy stored in glycogen there is almost a 90% difference F. Free Energy Change (ΔG) Revisited • ΔG is the difference between the fi nal and initial potential energies • In other words, it is the change in energy over a series of reactions • The difference between the energy on the product side and reactant side will produce a large ΔG (product side will be much lower than reactant side as energy is being released) Energy Release: • Chemical reactions move towards equilibrium ; the state in which the concentrations of the reactants and the products have no net change over time • As these reactions move towards equilibrium, they release energy • The diagram to the left talks about how there is a higher potential energy at the start of a metabolic pathway; at the beginning of a series of reactions there is much more potential energy • At the end of a series of reactions (metabolic pathway) there is going to be a much lower potential energy • Example: Aerobic glycolysis • We go from glucose, to pyruvate, etc. as more and more hydrogens are being cleaved off • The potential energy of the different substrates in this pathway are going to be less and less • There is going to be a decreasing about of potential energy as we go through this series of reactions • By the time you get to the end of the pathway, you want the substrate to have as little energy left as possible • Another example of this is in beta (fat) oxidation; as we go through the series of reactions there will be less and less energy associated with the fatty acid molecule • As you lose energy going through this series of reactions, eventually you get to a point where both sides of the equation are equal • At this point there is going to be no movement; no fl ux • The reactions will continue happening, but there will be the same amount of energy (a low amount) on either side of the equation Energy Coupling : • In our body, this is like a series of reactions • Coupling reactions involved retrieving some of the energy generated an using it to do work (rather than losing it all as heat) • An uncoupled reaction (rock example): • As the rock increases in speed and hits the bottom of the hill, the energy it possesses is then going to be released as heat (as the rock ‘explodes’) • A coupled reaction (rock example): • As the rock falls, the water wheel uses it’s weight to spin and create a levy by which the water can be lifted • There is always going to be a signifi cant amount of energy that is going to be lost as heat (however not as much energy will be lost when reactions are coupled) Energy Flux: • All reactions have reactants and products • All reactions will occur over some period of time (some may take longer, but there is always enough energy in the cell to maintain some sort of reaction) • Assume reactants A + B produce products C + D and that in the process, energy may be released • The more reactants you have (A + B) the faster the reaction will occur • ↑ A + B and ↓ C + D (i.e. a large -ΔG) cause the reaction to proceed rapidly to the right • Eventually, you will reach equilibrium; as the quantity of reactants decreases, the rate of the reaction decreases • As C + D builds up, the reaction will proceed more and more slowly; finally, the reactions is in equilibrium (ΔG = 0) • This forms a balance between the two sides of the equation How Can We Control Reaction Rate? • In exercise, we are very interested in controlling metabolic reactions • This means that we can control the rate of energy production • Two prime examples of controlling metabolic reactions are through substrate concentration and enzyme activity • We can control the rate of the reaction by just changing the volume/quantity of the substrate that is available; if we have a high amount of substrate available, the ΔG is going to be a lot higher, and the reaction will move toward completion at a much faster rate • More substrate = faster reaction • Another method by which we can control metabolic reactions (which, from a training perspective is particularly important) is looking at enzyme activity G. Enzymes • Enzymes are protein catalysts which help to regulate the rate of a reaction which would normally occur anyhow • The speed at which this enzyme will enable the reaction to occur is hundreds of times faster than if there were no enzyme • Enzymes are a method of controlling the rate of energy production; if the reaction is proceeding at a faster rate, we will be producing energy at a faster rate Action of Enzymes: • Many people think of the enzyme-substrate relationship as ‘lock and key’, however this is not entirely correct • The active site is continually reshaped by interactions with the substrate as the substrate interacts with the enzyme • The goal of the reaction to the right is to cleave the darker purple molecule into some variation of its components (two parts here) • The enzyme is critical for this reaction to occur (for the splitting of the molecule) • For every cleavage reaction there will be more products that there were reactants (example: started with A and ended with A and B) • In this case, we started with one molecule and ended with two • We end up with a greater number of substrates that could be used further down in the metabolic pathway • An example of this is in beta (fat) oxidation • At the highlighted point in the pathway to the left, NAD+ is going to pick up hydrogens from the substrate • The enzyme will be working in conjunction with the substrate; it will catalyze the cleavage of hydrogens to oxidize the NADH + H • Following this reaction, we’re left with a different substrate (3- ketoacyl coA) • So, the two products are the NADH + H and the resulting substrate How Do Enzymes Work? • Enzymes catalyze reactions by lowering the energy of activation • That is, the energy required to start the reaction is reduced • Note the difference in the energy of activation in the catalyzed reaction vs. the non-catalyzed reaction • With the presence of an enzyme, a reaction will occur much faster than it would on its own • A certain amount of energy is required for the reaction to occur • This certain amount of energy will be in the cell, so the reaction will, over some period of time, occur • The enzyme reduces the amount of energy that is required in order for that reaction to occur (the activation energy) • Left-hand side of the diagram: • Non-catalyzed reaction occurring without an enzyme present • Requires a signifi cant amount of energy input • Right-hand side of the diagram: • Catalyzed reaction occurring in the presence of an enzyme • When there is an enzyme present, that amount of energy that is required for the reaction to occur is going to be much less • An enzymes ‘mode of action’ is to reduce the activation energy required in a reaction Activation Energy (EA) : • Activation energy is depicted along the vertical axis • Without an enzyme Activation energy is large • With an enzyme Activation energy is small • Metabolic pathways can move extremely quickly and generate very large amounts of energy that they wouldn’t be able to do without the addition of an enzyme Temperature: • Another way to increase the reaction rate (on top the addition of an enzyme) is to increase the temperature of the cell itself • The body must maintain a temperature of 37°C at rest • Raising the temperature raises the average energy of A molecules, thereby increasing the reaction rate • If the temperature of the cell drops, the mount of energy that is available is reduced; reactions are going to occur at a slower rate • When the temperature is increased, the opposite happened; the amount of free energy that is available in the cell increases • As opposed to reducing activation energy (like enzymes do), increasing the temperature increases the energy that is readily available in the cell • This increases the reaction rate, since less energy is needed for the reaction to occur (has the same ultimate affect as an enzyme) Complex Control : • Enzymes provide a way to control the rate of reactions in the cell and thereby we can control the rate of energy production • However, the activity of some enzymes are under complex control • Feedback inhibition refers to a situation in which the substances at the end of a long series of reactions inhibits a reaction at the beginning of the series of reactions • A particular product downstream in a metabolic pathway is going to feedback and inhibit the reactions earlier in the pathway • As they inhibit these reactions, there will be a slower fl ux through that particular pathway, and therefore produce less energy and less product as a result • The affinity of the enzyme for the substrate will affect the rate of an enzyme catalyzed reaction • Specific enzymes will have a specifi c high-affinity or high attraction to a particular substrate within a metabolic pathway Example: Regulation of Glycolysis • In glycolysis, there are 10 different reactions that are going to occur • As a substrate goes through a series of reactions, there will be a molecules later on in the pathway that will act to inhibit the reactions above • An accumulation of acetyl coA will trigger the pathway above (breaking down carbohydrates) to stop • In other words, the accumulation of acetyl coA will down regulate the rate of the reactions earlier in the pathway • The same thing happens with ATP levels; as the levels of ATP increase in the cell, this will feedback and down regulate the metabolic pathway Enzymes (Cont’d): • The point in a metabolic pathway where ultimate control (slowest reaction) is exerted is termed rate-limiting, marker or regulatory enzymes • There are going to be specifi c enzymes known as rate-limiting, regulatory or marker enzymes that are going to dictate the fl ux through a particular path • Looking at anaerobic glycolysis for instance, one of the enzymes in this pathway is phosphofructokinase (PFK) • PFK is the slowest working enzyme in this pathway, so it will limit the rate of energy production from that particular pathway • SDH (hydrogenase) is another enzyme of a rate-limiting enzymes that is found in the Kreb cycle • It is the slowest acting enzyme in the Kreb cycle, therefore the fl ux through that particular pathway is going to be decided by its activity • These enzymes decide the ultimate speed of the metabolic pathway in which they work Control (Cont’d) : • Substrate concentration will affect the speed of a reaction • In this case, we have substrate concentration increasing, so therefore the speed of the reaction will also increase (direct relationship) • When you have very low levels of substrate available to the enzyme, any small change is going to see a signifi cant change in the speed of the reaction • If the amount of the enzymes is kept constant and the substrate concentration is then gradually increased, the reaction velocity will increase until it reaches a maximum • After this point, increases in substrate concentration will not increase the velocity (the reaction cannot go any faster) • This is because all of the enzymes is occupied (saturated); there is more substrate that the enzyme can deal with • The Michaelis constant (Km) is defi ned as the substrate concentration at ½ the maximum velocity • Below ½ Vmax, for every unit change in substrate concentration, there will be a greater change in velocity • After that point, for every unit change in substrate concentration, there is less of a change in velocity • ½ Vmax is like the tipping point Cofactors: • A non-protein component of enzymes is called the cofactor • If the cofactor is organic, then it is called a coenzyme • Coenzymes are relatively small molecules compared to the protein part of the enzymes • Many of the coenzymes are derived from vitamins (ex. acetyl coA) • The coenzymes make up a part of the active site, since without the coenzymes, the enzymes will not function • Cofactors are bound to the enzyme itself • If the cofactor is required and is not available, that particular reaction will not occur • They are molecules that are associated with particular enzymes that are required for that specifi c reaction to occur • They enzymes have to be a particular shape so that they can match up with the substrate; sometimes they need the help of an additional molecule to work with the substrate to enable that reaction to occur NAD and FAD: • Coenzymes include NAD and FAD • These molecules act to transfer chemical groups between enzymes; they transport hydrogens from the Kreb cycle to the ETC • Many coenzymes are derived from vitamins • NAD+ (Nicotinamide Adenine Dinucleotide) – Nicotinamide is from the vitamins niacin • The NAD+ coenzyme is involved with many types of oxidation reactions Riboflavin, Niacin and Pantothenic Acid : • These vitamins are found in many foods, and are critical for energy production • Metabolism requires certain vitamins, so nutrition is a very important source for energy production • Niacin is the core molecules of NAD • Without niacin, people aren’t able to transport hydrogens to the electron transport chain • Riboflavin is critical as far as the derivation of the FAD molecule • If you have a reduction in ribofl avin intake you will compromise the amount of FAD available for election transport, which will ultimately affect the energy production/consumption • Pantothenic acid is used as an acetyl group carrier • Without pantothenic acid, acetyl coA is unable to perform • All of these things can affect the rate of energy production during exercise H. Anaerobic Systems • ATP-PCr • ATP is a high-energy compound used to fuel exercise • ATP use can occur very rapidly • You split a phosphate off of ATP and energy is released • Maximal exercise comes purely from the breakdown of ATP (It is too short of a time period in order for aerobic systems to kick in) • Cells contain a storage form of high energy known as phosphocreatine (PCr) or creatine phosphate (CP) Energy Phosphate Potential : • We use this term to quantify the energy levels within the cell • How much energy is available to do exercise at any given moment in time? • As rest, the ratio of these high energy phosphates dictates how much energy is available • If you have more ATP that you do ADP and Pi, your energy phosphate potential is going to be very high • If you’re running as fast as you can for 3-5 seconds, the ATP concentration will decrease, but the concentration of ADP and Pi will increase greatly (because we breakdown ATP when our goals is to produce a high-energy output) • Energy level is going to decrease in this situation • During recovery, there will be an increase in ATP and a decrease in ADP and Pi Power and Duration: Exercise Physiology: Metabolism During Exercise (Lecture 3) Bioenergetics of Soccer : • Only 10% of the game is anaerobic; this indicates that the players are spending most of their time trying to recover • 80% of the game of soccer is low to moderate intensity aerobic exercise • The average heart rates are quite high (somewhere around 170 beats/min) • Even though the high intensity aspect is relatively short, it is still very intense (the athletes spend a lot of the time with very high hearts rates • It is dependent upon the position (i.e. defenders tend not to run as much as midfielders) Review (Last Lecture) GLUCOSE • Chemical reactions move towards equilibrium • As reactions move towards equilibrium they release energy • A metabolic pathway is a series of reactions that provide us with energy • The example of the water wheel is explaining that each reaction produces some amount of energy, and that amount of energy will decrease with every reaction PYRUVATE • From a substrate perspective, we have a glucose molecule • As we go through the metabolic pathways (aerobically), we’re trying to cleave off the hydrogens • There will be much less energy available from that particular substrate at the end of the pathway as we cleave more hydrogens off from that initial molecule (i.e. from glucose to pyruvate) • The number of hydrogens associated with the pyruvate molecule are much less that that associated with the glucose molecule Review: Coupling Reactions • We’re always generating and consuming ATP to maintain our body temperature (37°C) • So, if we’re going to do work, that energy is going to be over and above the energy that we use/consume at rest to maintain our body temperature • Not only are we generating heat, but we’re capturing some of the energy that is being made available through that series of reactions to do work Review: Controlling Reactions • Two prime examples are substrate concentration and enzyme activity or concentration • We need to be able to control energy production very precisely; this will depend on the particular sport that one is involved in • There will be enzymes between each of the products in the reaction above • Enzyme catalyzed reactions are much faster than non-enzyme catalyzed reactions • As far as the actual mechanism involved, there is a particular amount of energy that needs to be reached (activation energy) before the reaction can occur • The enzyme lowers the activation energy required for the cell to reach • The reaction may take hours to occur spontaneously, but in the presence of an enzyme it may occur 100’s or 1000’s of times faster • The inherent activity of the enzyme will dictate if the enzyme will work faster, breaking the substrate down faster, and making energy available sooner • The concentration of substrate can also affect the rate of reaction, and thusly, the energy production: • If you have a greater substrate concentration gradient at the beginning of the pathway, the rate of that reaction will be greater • The concentration of the enzyme can also help in controlling the reaction: • If we have more enzyme, we’ll be able to use more product up at a faster rate and can therefore increase the energy production • Cofactors are molecules that are associated either with the enzyme itself or with the substrate • They’re required because of conformational changes that happen to the substrate in order to produce the product • Sometimes, cofactors need to be added so that the substrate fi ts in with the enzyme • The temperature of the cell also affects the rate of the reaction: • Increasing the temperature in the cell increases the free energy that is available • Raising the temperature raises the average energy of the molecules, thereby increasing the reaction rate • In contrast, the average free energy of the molecules remains the same in un-catalyzed vs. catalyzed reactions (conducted at the same temperature) Review: Rate-Limiting Enzymes • These are also known as marker enzymes or regulatory enzymes • This is the point in a metabolic pathway where ultimate control (the slowest reaction) is exerted • This is because these enzymes work at the slowest rate • The Vmax (maximal velocity) that a regulatory enzyme works at is relatively low • The reaction rate that is inherent to the regulatory enzyme is relatively low • The concentration of these regulatory enzymes tends to be very high • The reaction rate within these regulatory enzymes is going to be affected by the substrate concentration that is used • Low substrate concentration = a low fl ux through the pathway (since the regulatory enzyme has a low rate of reaction) • High substrate concentrations = a high fl ux through the pathway) • So, for regulatory enzymes, Vmax is low but the concentration is high Review: Cofactors • Many organic cofactors (coenzymes) come from vitamins • The three vitamins that we focus on are niacin, ribofl avin and pantothenic acid • If you’re low in niacin or ribofl avin, that will compromise you’re ability to transfer those protons through the pathway (to the electron transport chain) • Pantothenic acid makes up acetyl coA; this is critical because acetyl coA is the entry substance into the Kreb cycle • The non-protein component of an enzymes is called the cofactor • If the cofactor is organic, then it is called a coenzyme • The coenzymes make up a part of the active site, since without the coenzyme the enzyme would not function • NAD+ = Nicotinamide Adenine Dinucleotide • Nicotinamide is from the niacin vitamin Review: Feedback Inhibition • Substrates that are produced at some point within the metabolic pathway will eventually accumulate • This accumulation of products will inhibit some previous reaction in the pathway • This is known as feedback inhibition Example: Regulation of Glycolysis • The accumulation of acetyl coA means that there is a relatively high fl ux through the pathway relative t the amount of energy that is being produced • As a result, the pathway is down-regulated • An increase in the amount of product at the end of the pathway leads to a decrease in the production upstream of that particular point • It is more efficient to breakdown glycogen as fuel, which will reduce the amount of glucose that we’re using • It is good to be able to conserve carbohydrates in that fashion Anaerobic Systems ATP-PCr (Immediate): • ATP is a high-energy phosphate compound within the cell that is used to fuel exercise • ATP use can occur very rapidly • When ATP is broken down (ATP ADP + Pi + energy) energy is made available • In order to re-generate ATP we need to re-phosphorylate ADP • Cells contain a storage form of high energy known as phosphocreatine (PCr) or creatine phosphate (CP) • PCr is broken down into its components (PCr P + Cr) and the phosphate from this breakdown will re-phosphorylate ADP to make ATP • So, ATP is broken down to give ADP and Pi • Then, the P from the breakdown of PCr can be joined with the ADP to give ATP very quickly • This is a recovery process • The rate of energy that you can produce from this pathway is very high, because there is only one reaction involved Power and Duration: • Right at the onset of maximal exercise you will be solely breaking down ATP (no recovery yet) • The exercise lasts just 1-3 seconds in duration • If the exercise were to last longer than just a few seconds, you would start using the phosphate from PCr to maintain ATP levels • The ATP-PCr system works in the first few seconds of maximal exercise • You’d be able to do that between 10 and 20 seconds of maximal exercise • After this point in time, you can’t get anymore energy from your ATP-PCr system, and need to get it from somewhere else (because you’re PCr levels become depleted) Details of Anaerobic Metabolic Pathways • ATP-PCr • We have a pool of ATP and of PCr in the muscle cell • The concentration of PCr is much greater than the concentration of ATP (4-5 times greater) • This system provides energy at a high rate but has a low capacity (i.e. total of 3-15 seconds in an all out sprint) • At the end of 15 seconds, you’re going to have depleted your PCr and will be unable to get energy regenerated from that pathway • During recovery, PCr must be regenerated • A phosphate (from ATP) will be joined with creatine • Ultimately, the ATP that was aerobically produced will be used to re- phosphorylate the creatine and enable you to maintain high-power outputs once again ATP and its Components • The diagram to the right shows the structural make-up of an ATP molecule, including the high-energy phosphate bonds • ATP is made up of an adenosine molecule and 3 inorganic phosphates (Pi) • There is energy associated with the bonds between the phosphates, so when they are broken, energy is released • There will be more energy released when the fi rst phosphate is cleaved, less when the second is cleaved etc. • The breakdown from ATP to ADP gives us the greatest amount of energy • The breakdown from ADP to AMP gives us less energy • This is why it is much more advantageous to have a greater concentration of ATP in the cell rather than ADP or AMP Breakdown of ATP • We need energy to be released; it is crucial for our bodies to do work in order to survive • When a phosphate is cleaved off of an ATP molecule energy is released • This breakdown of ATP occurs during exercise (we use ATP during exercise) • During recovery, this reaction goes in the opposite direction (NOTE: the red arrow); we have a re-generation of ATP during recovery • All the metabolic pathways are trying to re-generate this particular reaction in this direction • The more ADP that can be phosphorylated, the more energy we will have available for exercise • The different energy systems will dictate the rate at which you can release ATP or re-generate ADP Breakdown of PCr and Re-Generation of ATP • The diagram to the right depicts the mechanism for maintaining the levels of ATP from the energy stored in PCr • At this point, we have broken down ATP into ADP and Pi • PCr, in the presence of creatine kinase (enzyme), proceeds to the right, cleaving off Pi and leaving creatine (a little bit of energy is released) • That little bit of energy that it released from the breakdown of PCr allows for the re-phosphorylation the ADP using Pi to make ATP once again • You can produce very large quantities of ATP in a very short period of time, because there is only one reaction involved • The different metabolic pathways are all about the re-generation of ATP – how fast the various pathways can re-generate ATP is important • The ATP-PCr system involves very few reactions, and therefore has a very high rate of ATP re-generation • ATP concentrations do not drop dramatically (there is a little change, but not much) • This is because as soon as ATP is broken down, ADP is going to be phosphorylated by the breakdown of PCr • So, as opposed to seeing ATP concentrations dropping to zero, ATP concentrations are maintained in the cell at relatively high levels • However, PCr concentrations drop very low (almost to zero) • The great changes we see in the levels of PCr enable us to maintain the concentration of ATP – the Pi from the breakdown of PCr is used to re- phosphorylate ADP to make ATP, maintaining its concentration in the cell The Effect of PCr During Exercise • Along the horizontal axis of the graph is the change in PCr concentration during increasing intensities of exercise • Along the vertical axis of the graph is heat and work • As you do work, you are reducing the PCr in the cell and increasing the amount of heat • As the intensity of exercise increases, there will be a decrease in the concentration of PCr • The higher the intensity, the greater the decrease in the concentration of PCr • By looking at the PCr levels in the cell, we’re able to determine the level of intensity of the exercise • NOTE: ↑ exercise intensity = ↓ PCr [] Recovery • The products of the breakdown of ATP are ADP and Pi • During recovery, ADP can not only join with the phosphate from PCr to make ATP, but it can also join with another ADP to form ATP and AMP (monophosphate) • Adenylate kinase and myokinase are just two different names for the same enzyme • NOTE: this is all still part of the ATP-PCr system Figure 2.4 • This diagram shows the changes in muscle ATP and PCr during the fi rst few seconds of maximal muscular effort • By 10-14 seconds (9-11 repetitions) you reach a point where you can no longer move the weight you’re lifting • Initially (the fi rst 6 repetitions) the ATP levels are being maintained • After about 8 repetitions this maintenance becomes a little more diffi cult • At this points, ATP levels are starting to drop • We can maintain our levels of ATP in the early stages of maximal exercise, because we’re using the phosphate from the PCr to re-generate ATP • In a very short period of time, we reach failure (at around 10-11 repetitions) because PCr levels have gone from 100% concentration levels down to almost 0 (in the example of lifting weights) • NOTE: ATP levels do not reach zero (some say they don’t drop below 60%) • PCr levels can drop close to zero during high-intensity exercise, but there will always be a signifi cant amount of ATP in the cell • So then what’s causing failure/fatigue? (There are other mechanisms at work) Regulation of Glycolysis Revisited • We’ve talked about this as far as feedback inhibition; we already know that the pathway can be down-regulated by the products within the pathway • However, the pathway can also be regulated by the accumulation of high- energy phosphate compounds (i.e. ATP and ADP) • As ATP accumulates, it down-regulates the whole pathway • Down-regulation results in a decreased flux through the pathway • As ADP accumulates, it up-regulates the whole pathway • Up-regulation results in an increased flux through the pathway PCr Levels During Maximal Exercise: • This type of exercise occurs over a very short duration • PCr levels drop essentially to zero after about 10 repetitions or so • This is because we are utilizing the breakdown of PCr to maintain the levels of ATP in the cell (i.e. the ATP-PCr system) • Therefore, ATP levels are maintained in this type and duration of exercise • It is important to recognize that we’re talking about maximal exercise when we’re talking about the ATP-PCr system • We use ATP at the beginning, then use PCr to replenish the ATP levels, and eventually reach failure around 11 seconds PCr Levels During Continuous Exercise: • Example: riding on an exercise bike • How do the PCr concentrations change with differing intensities? (i.e. warm- up vs. sprint) • During warm-up, there is very little change in the PCr levels in the cell • During moderate exercise, there is still not much change in the PCr concentrations • However, there is a certain intensity at which you will start producing lactic acid; exercise will become more diffi cult • There will now be a drop in PCr concentrations (once you’ve surpassed the lactate threshold) • There will be a slow reduction in PCr concentrations in the cell • This is because when you’re doing endurance exercise and increase the intensity from moderate to heavy, you can dip into the PCr pool to help give you some of the energy required for that increasing intensity • Most of the work that you do during continuous exercise will come from the energy provided aerobically by the breakdown of fats, however, there is a pool of PCr in the cell that you can dip into to give you a little more energy • The pool of PCr in the cell is contributing a little but more to the energy that is being produced aerobically, therefore the levels of PCr
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