Different exercise intensities have different energetic demands. Thus, our body smartly counts on different energy systems that supply the working muscles to continue exercising. Each of them has different characteristics and becomes the primary supplier during certain situations.
Adenosine triphosphate (ATP), the well-known molecule, is utilized as the chemical energy source for actin-myosin interactions and most other endergonic, energy-requiring reactions in muscle such as Ca2+ transport from the cytosol to the sarcoplasmic reticulum (SR) and plasma membrane Na+-K+ exchange.
Despite ATP being the immediate source of energy for actin-myosin interactions and related processes of muscle contraction, all body cells function to maintain ATP homeostasis as best as possible in the face of ATP demand. Thus, regardless of the very rapid turnover, there is very little net change in muscle [ATP] during physical exercise.
The estimate of ATP storage capacity is very small (5-6 mMol/kg wet weight, which is less than 1.0 kcal/kg muscle) together with the absence of significative net [ATP] change leaves ATP out as a major muscle energy store form.
Then, cells must rely on other mechanisms to supply ATP to support their physiological functions, which involve the store of energy in more complex molecules.
There are three major energy systems responsible for the resynthesis of ATP:
- The Phosphagen System
- The Glycolytic System
- The Oxidative System
They all help to maintain the ATP homeostasis by resynthesizing ATP. However, they have different characteristics that make them function in different ways. It is important to point out that even though each of the different energy systems predominate over the others during certain situations, they do not work in isolation and the resynthesis of ATP is done by all three systems together contributing in different proportions.
Now, let’s review each of them carefully!
The phosphagen system
The phosphagen system is the simplest of the energy systems and its main substrate of the is the phosphocreatine (PCr), another high-energy phosphate molecule that stores energy. In contrast to ATP content, [PCr] is five to six times greater in human muscle (around 26 mMol/kg wet weight).
This simple pathway involves the transfer of an inorganic phosphate (Pi) from PCr to ADP to form ATP, a reaction that is catalyzed by the enzyme creatine kinase (CK).
Since CK is the rate-limiting enzyme in the pathway (and the only enzyme involved in it), and in concordance with the principle of negative feedback, creatine kinase activity is enhanced when concentrations of ADP increase, and is inhibited when ATP concentration increase.
When intense physical exercise begins, part of the pool of ATP is broken down to ADP and Pi. This enhances CK activity and PCr is catabolized to form new ATP and prevent its depletion. As exercise progresses and the other two energy systems (glycolytic and oxidative systems) become active, thus contributing more and more to the ATP resynthesis, creatine kinase activity is inhibited. It can even catalyze the opposite reaction when energy demands diminish: resynthesis of phosphocreatine by donation of an inorganic phosphate from ATP to creatine.
The phosphagen system occurs in the cytosol of the cell and does not need oxygen to take place. This is why it has been referred to as the anaerobic alactic pathway for a long time (alactic because it does not produce acid lactic as a byproduct, but creatine instead). Even so, this reaction has been observed to occur even in the presence of oxygen. Not only that but its regeneration also depends on the oxidative system, which requires oxygen. For this reason, it makes more sense to refer to it as the phosphagen system.
Because of the simplicity of this energy system made up by only one reaction, it allows the resynthesis of ATP at a very high rate. Thus, it is the most active energy system for power exercises, during which an extremely high rate of ATP turnover is required.
However, the capacity of the phosphagen system to maintain ATP levels does not last long. The combination of ATP and PCr stores can sustain the muscle’s energy needs for only less than 15 seconds during an all-out sprint. Beyond this time, muscles must rely on energy systems for ATP formation: glycolytic and oxidative pathways.
The glycolytic system
The second method of ATP production involves the breakdown of glucose through a sequence of reactions catalyzed by glycolytic enzymes. This energy system is called the glycolytic system since it entails glycolysis.
As stated above, the main substrate of the glycolytic system is glucose. However, this glucose can be taken up by muscles from blood glucose or produced by breaking down muscle glycogen stores through a process called glycogenolysis.
Depending on whether this glucose comes from blood or muscle glycogen stores, the process of glycolysis will yield either 2 or 3 ATP respectively. As shown in the image above, this is because before either glucose or glycogen can be used to generate energy, they must be converted to glucose-6-phosphate (G6P). When glucose is taken up from blood it has to be phosphorylated (which consumes an extra ATP), whereas when it comes from glycogen it already contains the phosphate, which saves the extra ATP used to add the phosphate group.
Apart from the ATPs generated, this system also reduces NAD+ to NADH (an electron- and proton-carrying coenzyme) which are subsequently transferred to the mitochondria for as substrates for mitochondrial respiration.
The glycolytic system requires about 10 reactions to break down glucose or glycogen to pyruvate, which is then converted to lactic acid through lactic fermentation, a reaction catalyzed by lactate dehydrogenase (LDH).
It has long believed that lactic acid is a waste product, but it has now been shown to be a beneficial byproduct of the glycolytic system. Its production in muscle is essential to remove pyruvate to prevent negative feedback, regenerate NAD+ to sustain high rate of ATP regeneration, and contribute to proton buffering among many others. If you wish to learn more about it, I wrote a full review of lactate’s physiological roles that you can have a look at.
Anyway, going back to our matter, the increased complexity of this energy system slows down the rate of ATP production compared to the phosphagen system but it is still a very rapid means of ATP regeneration compared to the oxidation system. Thus, it is the predominant energy system during speed exercises.
Similar to the phosphagen system, the glycolytic system does occur in the cytosol and does not need the presence of oxygen to take place. This is why it has been referred to as the anaerobic lactic pathway. However, I believe that this is not the appropriate term to refer to it since it also occurs when there is plenty of oxygen available and the removal of its byproducts (to prevent negative feedback) depends on the oxidative system, which requires oxygen.
Maximum ATP regeneration capacity through the glycolytic system is achieved when the rate of work requiring an energy load greater than an individual’s maximum oxygen uptake (VO2 max) is performed for as long as possible, which ranges from 30 seconds to 2 minutes.
However, both these two energy systems described so far are not capable of supplying all the energy needs for all-out activity lasting more than 2 minutes or so. Prolonged exercise relies on the third energy system: the oxidative system.
The oxidative system
The oxidative system involves the breakdown of carbohydrates, fat, and amino acids with the aid of oxygen to generate energy, a process called cellular or mitochondrial respiration. Because oxygen is required, this is an aerobic process and it has long been referred to as the aerobic system.
Unlike the two previous energy systems described above, the oxidative system occurs in the mitochondria.
Due to the high complexity of this energy system, it generates ATP at a slower rate compared to the other two systems. However, it has a much larger energy-producing capacity. Altogether, it makes it be the primary method of energy production during endurance activities, where the ATP demands are not that high but they last for a long period of time.
This requires a considerable demand of the cardiovascular and respiratory systems to deliver oxygen to the active muscles. I recommend you take a look at two previous articles about the two main cardiovascular responses during exercise that allow achieving such needs: increased cardiac output and blood flow redistribution.
As mentioned earlier, the substrates for the oxidative system are carbohydrates, fat, and amino acids. However, during normal exercising conditions, oxidation of amino acids accounts for no more than 5-10% of the total energy expended, so its metabolism is often considered negligible.
Oxidation of carbohydrates
The oxidation of carbohydrates involves three processes: the glycolysis, the Krebs cycle, and the electron transport chain (ETC). The two latter processes take place within the mitochondria, which means that the pyruvate obtained from glucose by glycolysis must be transported from the cytosol to there.
Once in the mitochondria, it is converted to acetyl-CoA, a two-carbon metabolite, by losing a carbon molecule, which produces energy in the form of NADH. Acetyl-CoA is the substrate of the Krebs cycle, through which it is completely oxidized to CO2. This yields 1 ATP, 2 NADH, and 2 FADH2 (another electron- and proton-carrying coenzyme) per molecule of acetyl-CoA.
Finally, the electrons carried by the coenzymes reduced during the oxidation of carbohydrates are passed to the complexes that make up the electron transport chain. The pass of the electrons from complex to complex, releases energy that is used to pump protons generated in the whole process from the mitochondrial matrix to the intermembrane space of the mitochondria. This generates an electrochemical gradient that then is used by the ATP synthase to regenerate ATP from ADP and Pi. It is estimated that oxidation of each NADH results in 3 ATPs whereas oxidation of each FADH2 results in a net 2 ATPs.
For the ETC to take place, oxygen must be present since it is the final acceptor of the electron passed from complex to complex. Therefore, ETC consumes oxygen and it will be impaired if oxygen lacks. This, in turn, produces a molecule of water per atom of oxygen that accepts an electron.
Overall, the oxidative system yields 38 or 39 ATPs depending on whether glucose came from blood or from muscle glycogen, respectively. However, since these high-energy molecules must be transported to the cytosol to be of any use and this process costs energy, a net gain of 32-33 ATPs has been estimated.
This whole process requires considerably more reactions than the roughly 10 reactions that the glycolytic system requires, which slows down the rate at which ATP is regenerated. This makes the complete oxidation of carbohydrates be predominant during events lasting longer than 2 minutes. Even so, as we will describe later, the oxygen demand for the oxidation of carbs is not as high as for fat oxidation. For this reason, and since oxygen delivery is limited by the oxygen transport system, carbohydrate is still the preferred fuel during high-intensity exercise.
Muscle and liver glycogen stores can provide only about 2,500 kcal of energy, which means that exercise duration will be limited by the quantity of glycogen stored and the rate at which it is used. It is estimated that carbohydrate stores are depleted in 90 minutes at an intensity of 75% VO2 max. For this reason, another substrate must contribute to muscle’s energy needs. This other substrate is fat!
Oxidation of fat
Unlike muscle and liver glycogen, fat stored inside muscle fibers and in fat cells can supply at least 70,000 to 75,000 kcal, even in a lean adult. This means that it is an almost unlimited fuel source for the organism.
Although many chemical compounds are classified as fat (such as triglycerides, phospholipids, and cholesterol) only triglycerides (TGs) are a major energy source. However, before they can be used for energy, they must be broken down to its basic units: one molecule of glycerol and three of free fatty acids (FFAs). This process is called lipolysis and it is catalyzed by lipases.
FFAs are the actual primary energy source for fat metabolism. Again, to be used for energy production they must be converted to acetyl-CoA in the mitochondria through a process called β-oxidation.
β-oxidation involves a series of steps in which two-carbon acyl units are chopped off of the carbon chain of the FFA coupled to the formation of one molecule of NADH and another one of FADH2. Then, the acyl units are transformed to acetyl-CoA, which subsequently enters the Krebs cycle for the formation of ATP in the same way that the one coming from the oxidation of glucose did. It should be noted that before FFAs enter the mitochondria, they must be activated through the addition of a Coenzyme A, which uses the energy of two ATP molecules.
As you have noticed, acetyl-CoA is the common intermediate through which all substrates enter the Krebs cycle for oxidative metabolism.
From the formation of acetyl-CoA, the oxidation of FFAs follows the same metabolic path than carbohydrates: Krebs cycle and ETC. Also, don’t forget about the requirement of oxygen for the ETC to occur and its subsequent formation of water.
As FFAs contain more carbon molecules than glucose, more acetyl-CoA is formed from an FFA and, consequently, more acetyl-CoA enters the Krebs cycle and more electrons are sent to the ETC. This is why the oxidation of fat generates much more energy than glucose metabolism.
However, fats are heterogeneous, and the amount of ATP produced depends on the specific fat oxidized. For example, the abundant 16-carbon FFA palmitic acid give rise to 106 ATPs (already transported to the cytosol) through complete oxidation, which is way greater than the 32 molecules of ATP from glucose or 33 from glycogen.
As you could have probably figure out by yourself, because an FFA molecule contains more carbon molecules than glucose, its complete combustion requires more oxygen. The energy yield from fat is 5.6 ATP molecules per oxygen molecule used, which is considerably lower compared with carbohydrate’s yield of 6.3 ATP per oxygen molecule. Thus, fat oxidation is predominant during low-to-moderate-intensity exercises, during which more oxygen is available.
Apart from that, the maximum rate of ATP production from lipid oxidation is too low to match the rate of utilization of ATP during high-intensity exercise. This explains the reduction in an athlete’s race pace when carbohydrate stores are depleted (commonly called bonking) and fat becomes the predominant fuel of source. Then, fat provides energy during longer and lower intensity exercise bouts.
Oxidation of protein
Carbohydrate and fat are the preferred fuel substrates. However, the amino acids that compose proteins are also used under some circumstances, especially when fasted. Even so, they do not account for more than 5-10% of the total energy expended and it is hard to assess the rate of protein metabolism. For this reason, estimates of total energy expenditure ignore protein metabolism.
Anyway, when using amino acids as an energy source, some of them can be converted to glucose and some others can be converted into various intermediates of oxidative metabolism to enter the oxidative process.
It is important to point out that whereas some of the released nitrogen is used to form new amino acids, the remaining nitrogen cannot be oxidized by the body and it is converted into urea and then excreted in the urine. This conversion requires the use of ATP, so some energy is spent in this process.
Interaction among energy systems
The three systems do not work independently of one another, and no activity is 100% supported by a single energy system. From the shortest sprints (less than 10 seconds) to endurance events, each of the energy systems is contributing to the total energy needs of the body, although one of them predominates under a certain situation.
As you probably noticed, there is a reciprocal relation among the energy systems with respect to power and capacity. The phosphagen system can provide energy at an incredible fast rate but has a very low capacity for energy production. Thus, it supports exercise that is intense but of very short duration. By contrast, fat oxidation takes longer to gear up and produces energy at a slower rate; even so, the amount of energy it can produce is almost unlimited.
Our body contains different systems of energy production to adjust the rate at which ATP is synthesized so that its consumption is matched to its production. Through the breakdown of phosphocreatine, the phosphagen system manages to compensate for the extremely high ATP demands during all-out sprints lasting less than 15 seconds. The glycolytic system, through the breakdown of glucose to pyruvate and lactate, reaches an ATP production rate that supports high-intensity exercise during less than 2 minutes. Finally, our body can completely oxidize glucose and fatty acids through the oxidative system to supply energy during longer yet less intense events.
Although only the latter energy system requires oxygen, the regeneration of the phosphagen and the glycolytic system also depend on the oxidative system. This is why I believe that the classic terminology of the energy systems on the oxygen requirement (anaerobic alactic, anaerobic lactic, and aerobic system) is out of date and the previously mentioned should replace it.
- Brooks, George A. 2012. “Bioenergetics of Exercising Humans.” Comprehensive Physiology 2 (1): 537–62.
- Baker, Julien S., Marie Clare McCormick, and Robert A. Robergs. 2010. “Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise.” Journal of Nutrition and Metabolism 2010
- Kenny, W. Larry, Jack H. Wilmore, and David L. Costill. 2012. “Fuel for Exercise: Bioenergetics and Muscle Metabolism.” In Physiology of Sport and Exercise2, 5th ed., 54–64. Champaign: Human Kinetics Publishers.