Bioenergetics + Metabolism

Some words to know

  • Bioenergetics is the flow of energy a biological system, and describes the conversion of macronutrients (carbs, protein, fat, which all contain chemical energy) into micronutrients (glucose, ATP) that can be used for energy. The energy is harvested from the breakdowns of chemical bonds within the macronutrients.

  • Metabolism is the total sum of all chemical reactions. Catabolism is the breakdown of large molecules into smaller molecules. Anabolism is the opposite of that, building large molecules from smaller ones.

    • Catabolic reactions are typically exergonic reactions, meaning they are energy-releasing. While anabolic reactions, as well as muscle contractions, are generally endergonic reactions which require energy.

  • Energy stored in the chemical bonds of ATP is used to power muscular activity. The ATP stored in skeletal muscle is replenished by 3 basic systems - phosphagen, glycolytic, and oxidative.


ATP - Adenosine Triphosphate

ATP is required for all muscular activity and growth, therefore its important to understand how exercise affects ATP hydrolysis and resynthesis.  The breakdown of 1 ATP molecule to yield energy is called hydrolysis because it requires 1 molecule of water.  The catabolism of ATP is facilitated by the enzyme ATPase.  Notice how the chemical reaction has arrows going in both directions, which means this is the reaction for both the hydrolysis and resynthesis of ATP.

ATP + H2O ← via ATPase → ADP + Pi + H+ + energy

ATP and a water molecule, with the help of ATPase, will become adenosine di-phosphate, inorganic phosphate, hydrogen, and energy.

ATP Replenishment Intro

ATP is replenished in the muscle cells by 3 different processes - the phosphagen system, glycolysis, and the oxidative system.  The phosphagen system and glycolysis do not require oxygen, and are therefore considered anaerobic, and occur in the sarcoplasm of the cell.  While the oxidative system is aerobic and requires oxygen, and occurs in the mitochondria.   Out of the 3 macronutrients, only carbohydrates can be metabolized for energy without oxygen, therefore making it essential for anaerobic metabolism.

The way this section is taught doesn't totally highlight the fact that all 3 energy systems are active at any given time.  The magnitude of each system's contribution to overall work performance depends mostly on the intensity of the activity, and also on the duration of the activity.

Phosphagen System

Creatine Phosphate (CP or PCr) is an energy reserve for rapidly replenishing ATP, and is stored in limited amounts in the muscle cells.  Creatine kinase is the enzyme that catalyzes the reaction.  This process is active at the start of all exercise, during the first 0-6 seconds.  Mostly used for short-term, high intensity activities.  

PCr → via Creatine Kinase → Creatine + Pi + Energy

Energy + Pi + ADP → ATP

Creatine kinase breaks down creatine phosphate, steals the inorganic phosphate, and produces energy.  The energy then adds the phosphate to ADP to synthesize ATP.


Glycolysis is the breakdown of carbs to resynthesize ATP. There are two sources of carbs in the body used for glycolysis: muscle glycogen stores and glucose from the blood. The glycolysis process is driven by many enzymatic reactions, and therefore takes a longer time to resynthesize ATP than the phosphagen system, which only requires one enzyme.  But glycolysis has a much higher capacity to produce ATP because of the abundance of glycogen and glucose.  Both glycolysis and the phosphagen system occur in the sarcoplasm and are considered "anaerobic".  

Pyruvate is the end result of glycolysis, and can be dealt with in two different ways depending on the intensity of the exercise. Although the names suggest the two processes depend on oxygen availability, that's not true because glycolysis itself doesn't depend on it, and its confusing and mean that someone named it such.  Glycolysis itself is anaerobic, not depending on oxygen, but pyruvate is handled differently depending on the availability of oxygen and the energy demands of the exercise.

Anaerobic Glycolysis | Fast Glycolysis: high intensity exercise, high energy demand, insufficient oxygen = pyruvate is converted into lactate

Aerobic Glycolysis | Slow Glycolysis: lower intensity exercise, lower energy demand, sufficient oxygen = pyruvate is shuttled into the mitochondria, converted into Acetyl-CoA and enters the Krebs cycle, also known as the citric acid cycle.

If demand is high and intensity is high, energy must be transferred more quickly, the body will depend on anaerobic glycolysis and convert pyruvate into lactate.  On the other hand, if energy demands and exercise intensity are low enough and enough oxygen is available, the body can shuttle pyruvate to the mitochondria to be oxidized.

Lactate clearance?

Glycolysis Energy Yields

The net reaction for anaerobic glycolysis, when pyruvate is converted into lactate, yields 2 ATP per glucose molecule and a lot of lactate.  The amount of lactate that results makes this process of glycolysis less preferred.

Glucose + 2Pi + 2ADP → 2Lactate + 2ATP + H2O

The net reaction for aerobic glycolysis, when pyruvate is shuttled into the mitochondria, yields 2 ATP per glucose.  It also results in other molecules that can be further manipulated and converted into ATP or used to synthesize energy.

Glucose + 2Pi + 2ADP + 2NAD+ → 2Pyruvate + 2ATP + 2NADH + 2H2O


Oxidative Energy System

The oxidative energy system is the primary source of ATP at rest and during low intensity activities.  At rest prior to exercise, ATP is replenished by this energy system using 70% fats and 30% carbohydrates as fuel, then there is  a shift toward using more carbs and less fat at the onset of exercise.  But after prolonged, sub maximal, steady-state exercise (slow, long distance running, for example), there is a shift away from carbs and back to fats, and to a much lower extent, to protein as well.  When looking at the full picture of metabolic fuel sources, protein does not play a significant role.  Its contribution is only slightly increased during long bouts of exercise, typically longer than 90 minutes.

The first step in oxidation of blood glucose and muscle glycogen is glycolysis. When there’s enough oxygen, pyruvate is moved into the mitochondria instead of being converted into lactate. In the mitochondria, pyruvate is converted into Acetyl-CoA then enters the Krebs Cycle, or Citric Acid Cycle. For each molecule of glucose, the Krebs Cycle produces 2 ATP, 6 NADH, and 2 FADH2.

Pyruvate + O2 → (in mitochondria) → Acetyl-CoA

After the Krebs Cycle, the NADH and FADH2 transport hydrogen atoms to the electron transport chain (ETC). There, the hydrogens are used to rephosphorylate ADP to ATP, meaning it helps to add a phosphate atom to the molecule. The actual process of the ETC, formally referred to as the oxidative phosphorylation, is just a lot of chemistry and not very important, we just care about the end product of this process.

1 NADH = 3 ATP | 1 FADH2 = 2 ATP

Overall, the oxidative energy system (glycolysis → Krebs Cycle → ETC) yields these slightly different results depending on the initial carbohydrate fuel:

1 blood glucose = ~38 ATP | 1 muscle glycogen = ~39 ATP

Beta Oxidation

Repeat after me: fat burns in a carbohydrate flame. This means that carbs are needed to tap into the oxidation of fats. During most exercise, fat remains an untapped source of energy because we have enough stored glucose or glycogen to fuel us through the workout. But during long duration exercise, like a long run or bike ride, you might run out of carbs and have to utilize stored fat. Hence fat burning in the carb flame — only after your body uses a significant amount of stored carbs, or if you have a very low-carb diet, will it transition into using fat.

The fuel for fat oxidation comes from triglycerides stored in fat cells that can only be broken down by the enzyme lipase to produce free fatty acids (FFA). The FFA are released into the bloodstream where they can enter muscle fibers and undergo beta oxidation. Once in the mitochondria, beta oxidation follows the same steps as glucose or glycogen oxidation: FFA is converted into Acetyl-CoA, which enter’s the Kreb’s Cycle to produce ATP, NADH, and FADH2. The NADH and FADH2 are brought into the ETC, where the hydrogens are passed around and eventually yield over 300 ATP molecules!

Protein Oxidation

Protein isn’t a significant source of energy for most activities. Its considered to contribute minimally during short-term activities, but can contribute anywhere from 3% to up to 18% of the energy requirements during prolonged exercise.

Protein is broken down into its building blocks, amino acids, which are converted into glucose via the process gluconeogenesis. From there, it follows the same fate as any other pyruvate molecule.

Energy Production and Capacity

As you’re already aware, the molecular source of energy and the process of production are dependent on the type of activity. Activities that are performed at a high power output, such as resistance training, require its energy supply to be available at a rapid rate and therefore rely almost entirely on the phosphagen system. While activities such as marathon running, that are low intensity and long duration, require a prolonged energy supply and rely mostly on the oxidative energy systems for carbs, fat, and protein.

There is an inverse relationship between a given energy system’s maximum rate of ATP production and its total production capacity. Meaning the faster it produces ATP, the ATP is is capable of producing. The phosphagen system has the highest rate of production, while the beta oxidative system has the highest energy capacity. But at no time during exercise or at rest, does any one system provide the complete supply of energy. The contribution of each energy system depends first on the exercise intensity, and secondly on exercise duration.

↑ rate of production = ↓ capacity

EPOC — Excess Post-Exercise Oxygen Consumption

Oxygen uptake is a measure of a person’s ability to take in oxygen and deliver it to the working tissues via the cardiovascular system, and the ability of those tissues to use the oxygen. During low-intensity exercise with a constant power output, oxygen uptake increases for the first few minutes then plateaus once a steady state is reached. Steady state means that oxygen consumption is meeting the demands. However, during these first few minutes before the plateau, there is an oxygen deficit, meaning oxygen intake doesn’t meet the demands. During this time, the energy must be supplied through anaerobic systems because the aerobic systems are slower to respond.

Once exercise stops, oxygen intake levels remain higher than they were at rest before exercise to make up for the oxygen deficit from the beginning of exercise. This is referred to as oxygen debt, or EPOC. Oxygen is needed to restore the body to its pre-exercise conditions, and so its important to understand what happened during exercise so that its easier to know what needs to happen during recovery.

During high intensity exercises, when the anaerobic energy systems are the primary contributor, the body is in oxygen deficit for the entire duration of exercise. However, the oxygen deficit doesn’t directly translate to the EPOC. EPOC is mostly dependent on the intensity, duration, and mode of exercise, as well as a few other and less important factors.

Metabolic Specificity Training

Metabolic specificity training is pretty much what it sounds like — using specific exercise intensities and rest intervals (work to rest ratios) to tap into specific metabolic energy systems. This is especially useful for training for a certain sport because its more reflective of the actual metabolic demands of the sport and the training will be more productive. There are two different methods — interval and combination training

Interval Training: predetermined intervals of exercise and rest; more work can be accomplished at a higher intensity

Combination training: adding aerobic endurance work to enhance the recovery of anaerobic athletes; may result in lower anaerobic performance, muscle girth, max strength, and speed + power related performance.

Screen Shot 2018-09-26 at 6.52.20 PM.png