Exploring the sources of power at the molecular level.
Exercise professionals devote fervent attention to learning the intricate mechanisms of muscle actions and understanding how the contractile proteins (such as myosin and actin) create force to do an array of exercises. But the source of that force—the biochemistry of energy—often remains a mystery. This column will discuss recent explanations that help demystify the processes happening at the molecular level, where cells channel energy from food into the work accomplished by exercise.
All life forms need energy to grow, move and maintain themselves. Thousands of energy-requiring processes occur continuously in cells to meet life’s demands. Energy can take on many forms in biological systems, but the energy currency that is most useful is known as adenosine triphosphate (ATP) (see Figure 1).
Cells cannot create ATP from scratch. The first law of thermodynamics dictates that total energy in the universe remains constant. Therefore, from the dietary foods eaten and digested, potential energy resides within cells in the chemical bonds of organic (that is, carbon-containing) compounds such as glucose (a simple sugar or a monosaccharide), glycogen (a complex sugar or a polysaccharide composed of hundreds or thousands of glucose molecules stored in the muscles, liver and brain) and fatty acids (saturated or unsaturated acids produced during the breakdown of triglycerides).
When these compounds enter energy pathways, some of the atomic bonds break or become rearranged, and energy is released and captured in the formation of ATP. ATP molecules are then used for cell functions such as supplying the energy for muscle contraction, building other complex molecules (in conjunction with enzymes), generating electrochemical messages in nerves, transporting substances across cell membranes and powering every activity in the cells. The energy for all these processes is liberated from ATP by removing the terminal inorganic phosphate (Pi) group from the molecule, leaving adenosine diphosphate (ADP) plus one proton (H+). This ADP is readily recycled in the mitochondria (power source organelles in cells) and also in the cytoplasm, where it is recharged again to ATP.
When the terminal Pi is broken from the ATP, a high level of energy is released (which is why ATP is called a high-energy molecule) that very closely meets the needs of a specific biological reaction. The outermost Pi groups on the ATP are held together with unstable bonds, meaning the energy is readily released when the Pi separates from the ATP (a process called hydrolysis because water is the splitting molecule that removes the Pi). During this molecular commotion, a little heat energy is lost to the cell surroundings, which the cell does not recapture. ATP is not much of a storage fuel. Rather, it is produced in one set of reactions and almost immediately consumed in another set of reactions, a process called coupling.
The major distinction to make when differentiating types of energy-yielding pathways is whether or not they require oxygen for ATP synthesis. Some metabolic pathways require oxygen and are said to be aerobic; they will not proceed unless oxygen is present in sufficient concentrations. Other processes do not require oxygen to proceed to completion and are said to be anaerobic. The important message is that oxygen can play a major role in some pathways and have little influence on others. It is ideal to have this diversification in cells so they can adapt to cellular energy needs (at least temporarily) in the absence of oxygen. The major energy-yielding pathways and oxygen requirements are summarized in Table 1.
Glycolysis, the breakdown of glucose by enzymes, is one of the most studied metabolic pathways in exercise science. Glycolysis is a series of 10 sequential reactions that allow the conversion of glucose to pyruvate. If the reactions begin with glycogen, the storage form of glucose, there are 11 sequential reactions (called glycogenolysis). Glycolysis can occur in most cells, and it does not require oxygen. It is the preferred energy-yielding process for most cells and is used when blood glucose levels are normal.
Glucose in the blood can be transported into cells with specialized glucose transporter carriers (i.e., GLUT proteins).Once in a muscle cell, the glucose is trapped within that cell by the attachment of a Pi group on glucose’s sixth carbon. It is interesting to note that glucose trapped in upper-body muscles cannot be removed to help meet energy needs in the lower body (and vice versa). So, if a client’s glycogen energy becomes depleted in one area of the body during a challenging workout, glycogen stores in other areas may still be plentiful—but they cannot be obtained. Interestingly, intense training bouts (such as sprints) lasting longer than 10 seconds will result in greater glycogen storage and thus improve exercise performance (Kraemer, Fleck & Deschenes 2012).
Glycolysis is a story of struggle, although healthy cells can perform it with ease. The first five steps in glycolysis are designed to weaken the atomic bonds, making the carbohydrate compound less stable and more willing to liberate its energy. Think of glycolysis as going uphill on a bicycle. Getting up the hill is somewhat challenging, but once on top it’s easy pedaling on the way back down. Glycolysis reactions function in the same way: the second five are the energy-yielding phase.
With sufficient oxygen present, the carbohydrate breakdown (called carbohydrate oxidation) will continue until completion. The initial step of aerobic metabolism begins with the conversion of pyruvate into acetyl coenzyme A or acetyl-CoA in the mitochondria. Acetyl-CoA then combines with oxaloacetate to form citrate. Citrate is the first metabolite of several reactions called the citric acid cycle or Krebs cycle. During the citric acid cycle, citrate undergoes several reactions that generate CO2 (metabolic waste expired during an exhalation), some hydrogen carriers known as NADH and FADH2 (which transport energy to synthesize ATP in the next metabolic pathway) and a little ATP (with the help of a GTP molecule) (see Figure 2).
The NADH and FADH2 hydrogen carrier compounds proceed to the electron transport chain (ETC), where a sequence of cytochromes (iron-containing proteins) harvest the chemoelectric energy through specialized reactions (during which protons are pumped into the intermembrane space of the mitochondrion). During this process, oxygen is the driving force that causes electrons to be shuffled through the cytochromes. Eventually, the electrons combine with oxygen to form metabolic water. The protons (H+) that were pumped into the intermembrane space are then pumped into the mitochondrial matrix by an enzyme called ATP synthase, which liberates energy to synthesize ATP (Figure 3).
Like aerobic carbohydrate breakdown, fat degradation (or fat oxidation) requires oxygen. Because fats are long carbon chains, fats begin their disassembly with a metabolic process called beta-oxidation. Beta-oxidation is analogous to a lumberjack chopping down some long “carbon” logs into more manageable acetyl-CoA, NADH and FADH2 compounds. These compounds go directly into the mitochondrion to yield ATP (via the same metabolic processes explained above).
Several diverse energy systems work in unison within the body to meet ATP needs, as shown in Figure 4. Depending on exercise intensity and oxygen availability, one system may be used more than others. However, let the final message of this column be a tribute to both the genius and the exceedingly complex nature of the “essence of energy for exercise.”