Bioenergetics: ATP, ADP, AMP

Adenosine is made up of adenine and ribose and is attached to 3 phosphates. ATP by itself doesn't give us energy. The two bonds between the three phosphates store and release energy by being broken.

The body contains all the raw materials needed to produce ATP. Food contains proteins, fats, and carbohydrates that can be broken down into ATP through a series of steps beyond digestion and absorption. The ATP, in turn, is broken down into smaller components to release energy and heat, then recycled back to the original ATP structure, much like a puzzle that can be pieced together, taken apart, and then put together again.

This process follows the first law of thermodynamics, also known as the law of conservation of energy, which states that energy can be changes from one form to another but cannot be created nor destroyed. Metabolism runs on anabolic (building process) and catabolic (breakdown process) reactions that form the cornerstone of human physiology.

ATP to ADP Plus Energy

The first step is to break adenosine triphosphate down into its simpler counterpart, adenosine diphosphate (ADP). That break requires an enzyme (a protein that catalyzes chemical reactions), which causes a chemical reaction to occur. In this case, the enzyme is ATPase (an enzyme that catalyzes the breakdown of ATP to ADP), which breaks the bond between the second and third triphosphates to release the stored energy. The phosphate-removal process, called dephosphorylation (the process of removing a phosphate), requires water (H2O). This is one of the reasons why water makes up 2/3 of the body weight. Importantly, the breakdown of ATP to ADP releases one acidic proton (H+).

ADP to AMP

In the compound ADP there are still two remaining phosphate ions, and the bond between them still contains stored energy. In extreme circumstances, this bond can be used to generate needed cellular energy as well.

Consider an all-out sprint lasting 10 to 15 seconds. At that intensity and duration, the body has energy needs that exceed what the ATP-ADP cycle can provide. ADP accumulates in the muscle as it cannot rephosphorylate back into ATP fast enough. To meet immediate ATP demands, the enzyme adenylate kinase (an enzyme that catalyzes the reaction between ATP and AMP to form two ADP and vice versa) takes two ADP molecules and converts them into one ATP through rephosphorylation and one adenosine monophosphate (AMP) through dephosphorylation. This reaction can occur in both directions. ADP + ADP <> ATP + AMP

However, when the cellular demand for energy remains high, ADP is unable to rephosphorylate back into ATP because it is not energetically favorable—meaning the cell cannot support the reaction efficiently at that moment. Instead, the ADP is dephosphorylated to AMP, a phosphate ion, and cellular energy. This reaction can occur in both directions.

ADP <> AMP + Pi + energy

AMP is not an ideal molecule to have in the cells. In extreme circumstances and with the addition of other enzymes, it can break down even further and create ammonia, which is toxic to the muscles and blood. The lone phosphate can also pose a problem since an accumulation of phosphates can cause muscle fatigue and limit physical performance.

AMP accumulation, and a rising ratio of AMP to ATP within the cell, may overall be undesirable, but, as previously mentioned, studies have shown that the oxidative stress can work to reprogram the cell and ultimately improve muscular endurance and the response to free protons and phosphate ions.

The Energy Systems

The body has three different energy systems: short-term, intermediate-term, and long-term. The systems overlap in virtually everything a person does, but it is important to understand each system individually to fully understand when they are the most active.

Imagine being asked to run at maximum effort for 6 minutes. Muscles have only enough stored ATP to last a couple of seconds. To manufacture more ATP as quickly as possible, muscles turn to phosphocreatine (PC) (a molecule found in muscle and brain tissue that donates its phosphate to ADP to form ATP). This process provides an instant source of energy—up to 30 seconds-worth, however, this source is quickly depleted. The muscle’s stored ATP plus its phosphocreatine are collectively known as the phosphagen system (The combination of a muscle’s stored ATP plus its phosphocreatine).

As muscles continue using phosphocreatine, glycolysis (The process of splitting a glucose molecule into a pair of pyruvate molecules), in which ATP is made from glucose (The smallest molecule a carbohydrate can be broken down into and used as an energy source), emerges as the primary energy source. This occurs about seven seconds into the run. During glycolysis, a series of chemical reactions allow the body to break the glucose molecule into two pyruvate molecules (a three-carbon structure formed by splitting a glucose molecule), producing a small amount of ATP for a short amount of time - around two minutes. It should be stated that the process of glycolysis produces protons (H+). Once cellular acidity rises, muscle power declines. Research has shown that the end product of glycolysis is always lactic acid.

The phosphagen system and glycolysis are anaerobic processes (a process that can occur without the help of oxygen), meaning that neither requires the presence of oxygen. These two energy systems cover the first two minutes of this 6-minute run. Now, if the goal is to run as fast as possible for the entire 6 minutes, another pathway to generate ATP is needed.

The body begins with the pyruvate made through anaerobic glycolysis (the process of splitting a glucose molecule into a pair of pyruvate molecules to produce two ATP when oxygen is low). With the addition of oxygen, it undergoes a complex series of steps to break down the pyruvate until it ends up in the mitochondria of the cell - where ATP is generated. This aerobic metabolism can now manufacture ATP until the end of the 6-minute run. In fact, as those minutes pass, the boy begins using stored fat in addition to glucose to generate ATP. How much stored fat used during these six minutes depends on an individual’s training status. If the run lasts longer than six minutes, stored fat will continue to be used for energy.

The overview of the three energy systems suggests a relatively clear transition from one system to the next, but the transitions are not so definitive. For example, with the 6-minute run, the phosphagen system initiates the activity, the anaerobic glycolysis boosts energy production, then the aerobic energy system would start providing ATP after just 10 to 20 seconds, reaching full power in about 60 seconds in highly trained athletes (evidence has shown that nonathletes may require 3 to 4 minutes to reach the same level).

It’s also important to note that most sports, and many fitness activities, are intermittent, not continuous. In a typical gym workout, for example, the phosphagen system can easily recover during sufficient rest periods. Routines like HIIT training, where rest intervals can be shortened, will see a different distribution of energy-system contributions based on the body’s ability to recover as the rounds compound.

It’s important to note that the goal of endurance training is to develop the body’s ability to use stored fat as the primary fuel source. Fat provides a virtually limitless supply of energy. Even an extremely lean athlete has enough stored bodyfat around the organs to fuel several days’ worth of movement. Burning a higher percentage of stored fat does not result in cellular acid buildup, as is the case when glucose is the primary fuel.

Energy Sources During Exercise

There are four primary sources of energy during exercise: glucose, fatty acids, lactate, and ketones (a by-product of fatty-acid metabolism that can be used for energy). Whether from dietary sources, supplements, or naturally occurring in the body, ketones play one key role in cellular metabolism - they produce ATP. The energy system primarily in use will determine which fuel source is the most efficient for energy production.

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