You should have a working knowledge of the following terms:
Introduction and Goals
The first tutorial on energy concluded with us looking at ATP, the molecule that supplies most of the energy for cellular work. Adenosine triphosphate (ATP) is the end product of cellular respiration, which is a catabolic pathway comprised of a series of steps that convert the chemical energy in glucose into the energy contained in ATP. This tutorial will focus on the breakdown of glucose, but keep in mind that molecules can enter the pathway at various points; therefore, glucose is just one of several sugars that can be broken down during cellular respiration. The available energy in glucose (and other sugars) resides within its electrons. These electrons (along with their energy) are removed and passed to intermediate electron carriers in a step-by-step process. These intermediates (e.g., NADH) and the concept of reduction-oxidation reactions (electron transference) will be addressed in this tutorial. By the end of this tutorial you should be familiar with:
- The general form of a redox reaction
- Redox and energy
- The role of NAD+ in conveying electrons
- Alcohol and lactic acid fermentation, and their exploitation
The term "redox" is short for the chemical process known as "reduction-oxidation." It refers to the transfer of electrons that occurs during many chemical reactions. Electron transfer is extremely important to the life of a cell. During cellular respiration, there is a relocation of electrons. This relocation results in the release of energy that is stored in food molecules, and the released energy is used to synthesize ATP. Remember the first law of thermodynamics, which describes the conversion of energy; you can't "make" energy but it can be moved around. Redox is one way that this is accomplished.
During many cellular reactions, energy changes are conveyed by electrons (molecules either gain or lose electrons). A molecule that gains an electron is reduced, meaning that there has been a "reduction" in its positive charge. This gain in electrons is termed reduction. A molecule that loses an electron is oxidized, and this loss of electrons is termed oxidation. You can remember this somewhat confusing terminology with the mnemonic "OiL RiG", where (O)xidized species (L)ose electrons and (R)educed species (G)ain electrons.
The general equation of a redox reaction is:
- Xe- + Y --> X + Ye-
In this equation, molecule "X" is oxidized and loses an electron (and energy), whereas molecule "Y" is reduced and gains an electron (and energy).
Some molecules have a very high affinity for electrons, therefore, they are more likely to oxidize other molecules. The affinity for electrons is termed electronegativity. The more electronegative a molecule is, the more likely it will become reduced by the addition of electrons in a chemical reaction.
Importantly, not only do electrons move from one molecule to another during a redox reaction, so does energy. Restated, a molecule that is oxidized loses energy, whereas the molecule that is reduced gains energy.
Redox and Combustion
Figure 1. Methane combustion. (Click to enlarge)
Methane (CH4; also known as natural gas) combustion releases energy, CO2 , and H2O as final products. This occurs in the presence of oxygen (O2; which is highly electronegative) every time one ignites a gas stove in a house supplied with natural gas. (This example was also used in Tutorial 16; Energy and Chemical Bonds)
The figure above illustrates the conversion of methane gas into CO2, H2O, and energy. Note that accompanying the transference of electrons, energy is released and it can do work (the reaction is exergonic). In the process of redox, methane is converted into carbon dioxide (which contains an oxidized form of carbon) and water (which contains a reduced form of oxygen). The electrons that are associated with oxygen in the water molecule have much less energy than they had when associated with carbon in methane; this energy difference is released as heat.
While heat is useful for cooking, it is not very useful for biological reactions. During redox reactions that occur within your body, a high proportion of the energy that is released is moved into other forms of chemical energy. However, heat is released as a by-product of these reactions because no reaction is 100% efficient.
Redox and Cellular Respiration
Oxygen is highly electronegative; it tends to pull electrons toward itself and away from other molecules. Consequently it takes energy to keep electrons away from oxygen. As the electrons move closer to oxygen, they lose energy and the energy that is released can be used to do work. Cellular respiration is actually a series of reactions in which electrons are sequentially moved from glucose (and its catabolic products) to oxygen, or in some cases, to an alternative terminal electron acceptor. In the process, energy is released. Restated, cellular respiration is a series of redox reactions in which energy is gradually made available to do work. The work done is the synthesis (anabolism) of ATP.
The general equation for cellular respiration is:
- C6 H12O6 + 6 O2 --> 6 CO2 + 6 H2O + energy
Think of this as a redox process. In this case, glucose is oxidized and oxygen is reduced. Remember, oxygen is highly electronegative (electrons are drawn to it). Ultimately, oxygen is reduced to form water and glucose is oxidized to produce carbon dioxide.
Although this redox reaction is written as one equation, it really happens in a series of steps. The reason for this should be evident from the previous two questions. That is, a high amount of energy is released from the oxidation of glucose and unless the body controls this oxidation, much of the energy is wasted as heat. Therefore the cell gradually oxidizes glucose in a series of controlled steps, and electrons (and accompanying energy) are gradually released. Restated, in the oxidation of glucose energy is gradually liberated and becomes available to synthesize ATP.
NAD+ and Electron Transport
The general equation for cellular respiration is quite simple, however, the overall process actually takes place in several stages in different parts of the cell. For example, hydrogen atoms (and accompanying electrons) are not directly transferred from glucose to oxygen. There are several intermediate steps, with intermediate oxidants (electron carriers). The most prevalent electron carrier is nicotinamide adenine dinucleotide. This electron carrier can exist in its reduced form (NADH) or as an oxidized positive ion (NAD+). NAD+ is free to pick up electrons, whereas NADH has two more electrons and an additional proton.
Figure 2. Oxidized and Reduced Forms of Nicotinamide Adenine Dinucleotide. (Click to enlarge)
A molecule of NAD+ or NADH is quite simple, consisting of two nucleotides (adenine, found in RNA and DNA, and nicotinamide) joined together. In the presence of the enzyme dehydrogenase and hydrogen, NAD+ can become reduced to NADH. The structure of the oxidized form is shown on the left side of this figure, and the right side shows that portion of the molecule where reduction occurs.
NAD+ functions as an oxidizing agent (electron acceptor) during cellular respiration, picking up electrons from the catabolic products of glucose (along with hydrogen atoms). Each NAD+ molecule can be reduced with two high-energy electrons and one hydrogen atom. Importantly, once the transfer is complete and the reduced NADH has deposited its electrons, the regenerated NAD+ can pick up more electrons and begin again. In other words, NAD+ acts as an energy shuttle. Think of this process in the following way:
- XH2 + NAD+ --> X + NADH + H+
In this example, "X" is any molecule that gives up an electron and two hydrogens. Note that there is a single proton, H+, which remains unpaired after this transaction. These protons (hydrogen ions) accumulate and are very useful in certain stages of respiration (to be discussed later).
What Do We Know So Far?
We are now prepared to discuss the actual steps of cellular respiration. You should know:
If you are comfortable with all of these concepts, it's time to move on. If not, review those concepts that do not make sense.
The Stages of Cellular Respiration
Respiration can be broken down into three metabolic stages:
2. The Krebs, or Citric Acid cycle
3. Electron transport and oxidative phosphorylation
In the eukaryotic cell, glycolysis (stage 1) occurs in the cytosol (the protein-rich, semi-fluid part of the cell in which the cell's organelles are immersed), whereas the Krebs cycle, electron transport, and oxidative phosphorylation (stages 2 and 3) occur in the mitochondria (discussed in Tutorial 23). While our discussion will focus on cellular respiration in the eukaryotic cell, you should note that this process also takes place in prokaryotes (even though they lack mitochondria).
Sometimes glycolysis is presented as a process separate from cellular respiration, so don't be confused if you hear someone mention "glycolysis and cellular respiration."
Glycolysis: The First Step in Cellular Respiration
Glycolysis involves the initial breakdown of glucose to pyruvate (or pyruvic acid), water, and reduced electron carriers (in this case NADH). Ingested carbohydrates are first broken down by your saliva, and then by enzymes in your stomach. Glucose, from your food, is then taken into your cells, and during glycolysis is split into two 3-carbon molecules of pyruvate. Glucose is not the only sugar used by your body; other sugars are either converted to glucose or introduced at other points in the glycolytic pathway. Likewise, fats and proteins can be used as energy sources. These foods are catabolized and the metabolic breakdown products enter the cellular respiratory pathway at various points. We will begin with glucose because it makes use of all the metabolic steps, and hence illustrates the complete process of cellular respiration.
Glycolysis is initiated by the addition of a phosphate (P), from ATP, to a molecule of glucose; this destabilizes the glucose molecule and the bonds are then easily broken to release energy. So while there is a net gain of ATP in cellular respiration, some ATP is used to start the process.
Figure 3. Generalized Diagram of Glycolysis. (Click to enlarge)
Glycolysis is a ten-step process, but all of the specific intermediate molecules and enzymes involved won't be discussed here. However, you should understand the general way in which ATP is produced during glycolysis. At two steps, a phosphorylated molecule (e.g., the substrate PEP in the figure) transfers a phosphate group to ADP. This substrate-level phosphorylation can only occur in the presence of a specific enzyme (which differs according to the particular substrate that is donating the phosphate).
It takes two molecules of ATP to break down one molecule of glucose to pyruvate. The output is four ATPs and two NADHs. Therefore, there is a net gain of two ATPs and two NADHs from one molecule of glucose from glycolysis alone. Most of the energy remains in the pyruvate molecule.
This figure shows the overall energy "balance sheet" for glycolysis. Note the initial "investment" of energy in the early stages, which requires 2 ATP molecules per molecule of glucose. In the later stages, 4 ATP molecules and 2 NADH molecules are produced, which yields a net production of 2 molecules of pyruvate, 2 molecules of ATP, and 2 molecules of NADH per molecule of glucose.
Figure 4. Glycolysis Energy Assessment. (Click to enlarge)
As mentioned, one of the products of the initial breakdown of glucose is pyruvate. Pyruvate is further modified and enters the next stages of cellular respiration (the Krebs cycle and the electron transport chain). It is at these stages that most of the ATP is produced for cellular work. Probably because of its connection to the production of chemical energy, pyruvate has become a very popular nutritional supplement among dieters and body builders. The merits of pyruvate are greatly disputed. For general interest, you may want to do a Google search for "Pyruvate" for interesting comparisons of popular claims to actual research.
Glycolysis generates ATP without using oxygen as an electron acceptor. Restated, glycolysis can occur whether oxygen is present or not and whether conditions are aerobic or anaerobic. Pyruvate has two general fates: it can be further oxidized (in which case, more energy is obtained) or it can be further reduced (and discarded as waste).
The process by which glucose is partially broken down and NAD+ is regenerated is fermentation. The many types of fermentation differ in the waste products that are formed when pyruvate is broken down. Fermentation can occur in the presence or absence of oxygen. Many bacteria only carry out fermentation in the absence of oxygen, whereas yeast will ferment in the presence or absence of oxygen. Two common types of fermentation are alcohol fermentation and lactic acid fermentation. In alcohol fermentation, pyruvate gives off carbon dioxide and is converted to ethyl alcohol (ethanol) in a two-step process. In lactic acid fermentation, pyruvate is converted to lactate (lactic acid). The figure below depicts both types.
Lactic acid fermentation is used to make cheese and yogurt. Alcohol fermentation is used to make beer and wine.
Figure 5. Two Common Types of Fermentation. (Click to enlarge) Lactic acid fermentation is used to make cheese and yogurt. Alcohol fermentation is used to make beer and wine.
Humans capitalize on both of these fermentation processes. Yeast undergo alcohol fermentation in the production of beer and wine. Certain bacteria and fungi undergo lactic acid fermentation, and are used to make cheese and yogurt (discussed in Tutorial 20). There are many facultative anaerobes that can switch between fermentation and complete cellular respiration, depending on their environment.
We've concluded "part two" of our discussion on energy and cellular respiration, specifically by addressing redox reactions, NAD+ and glycolysis. You should be able to update "What Do We Know So Far?" with the following:
- Where glycolysis occurs in the cell
- The reactants and products involved in glycolysis
- The energy input and output of glycolysis
- What is meant by substrate-level phosphorylation
- How much ATP is produced in the absence of oxygen
If you're comfortable with these concepts, it's time to complete the discussion of cellular respiration in the next tutorial.