6.1 ATP Production – The energy transfer process

CHAPTER 6: Basics of Human Metabolism 6.1 ATP Production – The energy transfer process

As previously mentioned, the primary objective of most metabolic activities is to produce ATP.

ATP consists of an adenosine molecule linked to three phosphate molecules. The bonds between the adenosine and the three phosphates are considered “high energy.” Energy is released when the carbon-hydrogen bonds in carbohydrates, fats, and proteins are broken and when the adenosine-phosphate bonds are broken. Consequently, when ATP is utilized for cellular tasks, one adenosine-phosphate bond is broken, resulting in ADP (adenosine connected to two phosphates) and a free phosphate (P) present in the cell’s cytoplasm.

Although ATP is essential, only a small amount of it is stored in our cells. In fact, it is estimated that our entire body contains only about 80-100 grams of ATP. At the same time, we can store up to 5-6 times more Creatine in the body, mainly in our muscle tissue. This amount is sufficient for just a few seconds of maximal exercise like short-range sprinting or performing two vertical jumps. Moreover, we use such a significant amount of ATP daily – approximately 51,000 g (or 112.5 lb) for a 70kg (150 lb) individual – that the total weight of ATP consumed and regenerated would equal around 75% of our body weight.

As a result, when adenosine-phosphate bonds are broken, they must be rapidly regenerated to provide energy for our daily needs. This is where energy transfer processes come into play. These processes reattach the free AD and P in the cytoplasm, regenerating the broken ATP.

Despite its complexity, the body has two simple objectives: to break the carbon-hydrogen bonds in our carbohydrates, proteins, and fats and to utilize the released energy to regenerate adenosine-phosphate bonds, forming ATP. All life can be distilled down to this straightforward exchange of breaking and repairing chemical bonds. It is that simple (even though life often seems complicated).

There are multiple ways to achieve this process. The primary differences between the various ATP-producing systems are:

the speed at which energy is required;
the rate at which the reactions occur; and
the availability of sufficient oxygen to participate in the reaction.

To better understand how this works, we have outlined the main energy transfer processes or pathways within the body in the next few pages.

Did you know that the human body recycles its own body weight equivalent in ATP each day.

Törnroth-Horsefield, 2008

6.1.1. ATP-PCr System or the Phosphocreatine anaerobic system (anaerobic phosphagen system)

As the body starts utilizing ATP at a faster rate than usual, such as during physical activity or intentional exercise, the ATP/PCr system is typically the first to activate. This system, which functions in our cells’ cytosol, aids in the swift regeneration of ATP from ADP and phosphate (P). Creatine kinase, an enzyme, is used to break the chemical bonds between creatine (Cr) and phosphate (P) molecules already combined in a phosphocreatine molecule (PCr). Breaking these bonds releases Creatine, phosphate molecules, and energy into the cell. This energy and the newly released phosphate molecules help regenerate ATP to meet the increased physiological demand.

However, the newly generated ATP can only support the body for a brief period. Although the body’s PCr supply is about six times greater than its ATP supply, during periods of intense energy demand, such as maximal effort muscle contractions, it can only provide energy for approximately 10 seconds. The ATP-PCr pathway is best represented by activities like sprinting or heavy weightlifting, which requires rapid energy release. After about 10 seconds of all-out sprinting, the body must slow down due to the depletion of both ATP and PCr in the muscles.

Creatine supplementation can enhance muscular performance because it increases the intramuscular creatine pool, making more Creatine (and PCr) available for high-intensity, short-duration muscle contractions. Studies have demonstrated that higher concentrations of intramuscular creatine correlate with improved force during maximal contraction and increased endurance during high-intensity exercise. If you continue running and push yourself, you’ll find that you can keep going, albeit at a slower pace and with a “burning” sensation in your muscles. This is because your body seeks alternative energy sources, activating other metabolic pathways to help replenish both PCr and ATP stores. The pathways discussed below can sustain your activity, but they generate ATP more slowly than the ATP-PCr system. The ATP-PCr energy system is primarily associated with Type II muscle fibers, also known as fast-twitch muscle fibers. These fibers are specifically designed to generate rapid, powerful contractions and are suited for high-intensity, short-duration activities. Fast-twitch muscle fibers are further classified into Type IIa and Type IIx (often referred to as Type IIb). Type IIx, or fast glycolytic fibers, are the fastest contracting and most powerful muscle fibers. They have the highest capacity for anaerobic energy production, making them the primary muscle fibers associated with the ATP-PCr system. These fibers rely heavily on the ATP-PCr system and anaerobic glycolysis to generate energy, resulting in rapid fatigue.

6.1.2. Anaerobic glycolysis - Lactic Acid System

As the energy demands remain high beyond the initial ten seconds and phosphocreatine stores start to deplete, another energy system steps in to support ATP regeneration. Interestingly, the glycolytic system is activated alongside the ATP-PCr system. However, it contributes less to energy transfer within the first ten seconds of exercise since it regenerates ATP at a slower rate. The glycolytic system, which takes place in the cytosol, breaks down stored muscle glycogen, readily available blood glucose, and glycerol from triglycerides to help regenerate ATP. As the name suggests, glycolysis involves the breakdown of glucose. The glycolytic system is more complex than the ATP-PCr system, employing ten enzyme-controlled chemical reactions to regenerate ATP. Specifically, this process generates four ATP molecules (from ADP and P) for every glucose molecule that goes through the system. However, glycolysis requires two ATP molecules, resulting in a net gain of two ATP molecules per glucose molecule. Additionally, glycolysis produces two molecules of pyruvate and two molecules of NADH. When pyruvate is generated, the final step of the glycolytic pathway, a crucial decision point, is reached.

During high-intensity activities, glycolysis runs quickly, producing a large amount of pyruvate. This rapid glycolysis helps regenerate more ATP. It also releases numerous hydrogen ions into the cell as a byproduct, which can cause muscle fatigue. To counteract this, natural hydrogen acceptors NAD+ and pyruvate step in, transforming NAD+ into NADH and pyruvate into the well-known lactic acid. Contrary to popular belief, lactic acid serves as a hydrogen buffer, carrying hydrogen ions out of our cells and allowing us to continue exercising. Through the process from glucose to pyruvate and lactic acid, glycolysis can regenerate ATP and sustain intense physical activities for approximately 80 seconds after the initial ten-second burst provided by the ATP-PCr system. However, around the 80-second mark, hydrogen ion production increases muscle acidity to a level that slows down contraction rates. At this point, additional energy transfer systems must take over, albeit slower, requiring reduced exercise intensity. Examples of exercises or sports that rely on the glycolytic pathway include activities lasting between 30 seconds and two minutes, such as 400-meter sprints, middle-distance swimming, or high-intensity interval training (HIIT) workouts. When the glycolytic pathway operates at a slower pace due to moderate energy demands, pyruvate, and NAD+/NADH follow a different route. As a result, they contribute to the next ATP regenerating process, oxidative phosphorylation.

6.1.3 Aerobic Glycolysis, Krebs Cycle and the Electron Transport Chain - The Oxidative Phosphorylation Pathway

As maximum exercise activity continues beyond approximately 80-90 seconds, the intensity must decrease due to three factors: depletion of PCr, reaching the maximum rate of glycolysis, and elevated muscle acidity. At this point, a slower pace is required. However, if moderate exercise is maintained, oxidative phosphorylation comes to the rescue. As long as oxygen is available, this pathway can continue indefinitely. While the ATP-PCr system provides the initial ten seconds of energy and glycolysis is occurring, oxidative phosphorylation gradually increases to meet the growing energy demands. Although it’s the slowest energy transfer system, it has a remarkable capacity for ATP regeneration. In essence, if the ATP-PCr system is a 100-meter sprinter, the oxidative phosphorylation system is an ultramarathon runner. The oxidative phosphorylation pathway consists of the Krebs cycle and the electron transport chain. When the rate of glycolysis aligns with the rate of Krebs cycle activity, pyruvate is funneled into the Krebs cycle instead of being used to create lactic acid. Pyruvate from carbohydrate breakdown (via glycolysis) is converted into a compound called acetyl-CoA. Fats and proteins can also be broken down into acetyl-CoA through beta-oxidation and other processes, making acetyl-CoA the entry point for the Krebs cycle. The cycle, which occurs in the mitochondria’s inner chamber, regenerates one ATP molecule, creates two carbon dioxide molecules, and releases eight hydrogen ions with each rotation. A significant number of hydrogen ions are generated during the Krebs cycle. However, unlike those produced during glycolysis, these hydrogen ions do not cause immediate fatigue. Instead, they bind to NAD+ and FAD+ molecules within the mitochondria. They are quickly transferred to the next part of the oxidative phosphorylation process: the electron transport chain, where cellular efforts come to fruition. NADH (NAD+ and hydrogen) and FADH2 (FAD+ and two hydrogens) formed during the Krebs cycle transport these hydrogens through the mitochondria and transfer their energized electrons to a series of specialized molecules (cytochromes) in the cristae of the inner mitochondrial membrane.

These hydrogen molecules (specifically, their electrons) move between the cytochromes, and the energy they release is used to pump hydrogen molecules (their protons) from the inner chamber to the outer chamber of the mitochondria. This seemingly wasteful action serves an essential purpose. As protons accumulate in the outer chamber, they forcefully rush back into the inner chamber through a carrier called the ATP synthase complex, like water rushing through a dam. This influx of hydrogen protons produces a substantial energy yield, generating an impressive 32 ATP molecules per glucose molecule.

The three processes just described are the primary energy transfer mechanisms necessary for living, breathing, and moving. The electron transport chain, generating 32 ATP molecules, outshines the two ATP molecules produced by the Anaerobic glycolysis, and those two generated during the Krebs cycle. However, all three systems are crucial, working together to convert one glucose molecule into 36 ATP molecules. Although all three systems are constantly active, the energy demands of maximum exercise push them to operate at their highest speed and efficiency. When this speed or efficiency is compromised (due to nutrient deficiencies, enzyme deficiencies, or mitochondrial inefficiencies), metabolic rate, overall health, and physical performance are affected. Practical examples of exercises or sports that rely on the oxidative phosphorylation pathway include activities that require sustained aerobic efforts, such as long-distance running, cycling, swimming, or cross-country skiing.

Beta oxidation

When energy transfer requires fatty acids, they undergo a process called beta-oxidation. This procedure breaks down fatty acids into acetyl-CoA, a vital molecule in energy transfer. Fatty acids are composed of long carbon-hydrogen chains, and acetyl-CoA consists of only two carbons. Thus, typical fatty acids can generate a significant amount of acetyl-CoA. For instance, a 16-carbon fatty acid would yield eight units of acetyl-CoA. During the detachment of two carbon units from fatty acids, NADH and FADH2 are created, similar to glycolysis. These molecules then convey their hydrogen ions to the electron transport chain, regenerating ATP. Lastly, the acetyl-CoA produced during beta-oxidation is incorporated into the Krebs cycle. The resulting byproducts support ATP regeneration through the electron transport chain. Although beta-oxidation closely resembles the glycolytic process, it regenerates considerably more ATP than glycolysis. In fact, a single 18-carbon fatty acid can generate roughly 146 ATP molecules. Given that triglycerides comprise three fatty acid molecules, the total amounts to 438 ATP molecules per triglyceride. Glycerol also contributes to ATP regeneration, adding 19 more ATP molecules, resulting in the breakdown of each triglyceride producing an impressive 457 ATP molecules. Compared to the 36 ATP molecules generated by one glucose molecule, fat emerges as an ATP powerhouse. However, it is essential to note that fat oxidation can only occur at these rates if oxygen is present, rendering this process aerobic. Oxygen must be available to accept hydrogen ions after they participate in the electron transport chain. Suppose the energy transfer rate surpasses oxygen availability in high-intensity anaerobic work. In that case, beta-oxidation ceases, and the body primarily relies on glucose oxidation through glycolysis, an anaerobic process. Although fat oxidation is efficient, carbohydrate oxidation takes precedence during high-intensity activities for this reason.

Carbohydrate, Fats and Proteins as Fuel Sources

Our bodies mainly rely on carbohydrates (CHO) and fats in the form of free fatty acids (FFA) as primary fuel sources. Although proteins can be utilized for energy, this happens rarely and under specific conditions. Protein breakdown for fuel is unlikely unless the body has exhausted its carbohydrate stores, such as liver and muscle glycogen, and body fat stores are extremely low.

Protein breakdown for energy may occur during extended fasting periods or low carbohydrate intake when carbohydrate stores are depleted. In these cases, the body starts breaking down proteins (muscle tissue) to generate glucose through a process called gluconeogenesis. This phenomenon can also occur during prolonged physical activity when carbohydrate and fat stores are insufficient. If the activity continues, the body may rely on 10-15% of its energy needs from protein stores (primarily muscle tissue). Lastly, protein breakdown for energy may happen during insufficient calorie intake, leading to muscle loss due to a prolonged period of low-calorie dieting. This causes protein breakdown for energy and amino acid transition into glucose to ensure essential body functions.

As personal trainers, avoiding circumstances that lead to protein breakdown should be one of our priorities. Recognizing situations where it may occur and taking appropriate action to counteract protein degradation is essential. Dietary interventions play a crucial role in ensuring optimal health and performance for clients. We encourage all personal trainers to educate themselves in nutrition to provide a higher level of service.

In a resting state, our bodies primarily use fat as the main energy source (approximately 60-70%), with carbohydrates contributing to a lesser extent (approximately 30-40%). The exact ratio depends on various influential factors.

The body’s energy source during exercise depends on factors like intensity, duration, and substrate availability, as suggested by studies (Spriet, 2014). At higher intensity levels, the body primarily uses carbohydrates for energy, derived from muscle glycogen stores, which typically suffice for the first 20-30 minutes of exercise above 80% of maximum effort.

It’s essential to understand that our bodies continuously shift between fuel sources based on intensity levels and duration to meet the ongoing energy demands.

Previous Lesson

Back to Lesson