Harvesting Chemical Energy
- Cellular Respiration -

     Why do we eat? Why do we breathe? Why do cells need energy? How do cells gain access to energy? These are some of the questions which you can ponder as we move through this section of the cellular world. Cells have the machinery to manipulate molecules and the bonds within them. As covalent bonds are rearranged energy is released. This energy is harvested by different means in different cells. The goal is to replenish the ever dwindling supply of ATP which is necessary to perform "work" in the cells. Most cells have a biochemical pathway referred to as cellular respiration.

Metabolic pathways:
     Role of enzymes. Each step in the pathways is catalyzed by a specific enzyme.

Catabolic versus anabolic pathways

• Catabolic reaction harvest energy as well as building blocks by breaking down molecules. Energy is needed for different forms of work, e.g. anabolic reactions, transport processes, movement.
• Anabolic reactions use the energy and the building blocks to make molecules.

Energy carriers: The cell has numerous molecules which are able to “hold” energy. The most common type is adenosine triphosphate (ATP) which is used in most processes which require energy within the cell. Other examples are NADH and FADH2 which carry substantially more energy than ATP. As you know the energy in the latter two molecules is transferred to ATP in the electron transport chain.

Release of energy: Evolution has led to a number of metabolic pathways able to change the structure of molecules. In the process of change the energy trapped in the covalent bonds of the molecule is transferred to various other molecules such as ATP, NADH and FADH2. This is all accomplished with the help of specific enzymes. Recall that enzymes specifically fit their substrate as they connect via the active site.

Cellular Respiration: a process able to extract a large amount of energy from food molecules.  In eukaryotic cells oxygen is a required component. This metabolic process is the main reason that animals have elaborate gas exchange organs such as lungs, gills and other systems. The goal of these systems is, of course, to get access to oxygen and to get rid of carbon dioxide.

    The equation above represents the input and output, i.e. the final outcome of the process.  As you can see the glucose molecule is completely oxidized to carbon dioxide and water. Of course, to accomplish the complete breakdown of glucose it is necessary to use numerous small steps. The glucose molecule contains an enormous amount of energy and it is simply not possible to release all the energy at once. Instead the numerous steps in the metabolic pathways allows the energy to be captured in small increments as they are transferred to ATP, NADH and FADH2.
Cellular respiration is composed of three components:

• i) Glycolysis
• ii) Krebs Cycle (also called the Citric Acid Cycle or the TCA Cycle)
• iii) The Electron Transport Chain (ETC)

The Krebs Cycle:
    These pathways represent changes in organisms over evolutionary time making it possible to extract further energy from the pyruvate molecules.
     In bacteria the Krebs Cycle occurs in the cytoplasm while in eukaryotic cells it occurs in the matrix of the mitochondria. Consequently, the pyruvate molecules (formed in the cytoplasm) need to be transported into the mitochondria.
    The Krebs cycle is preceded by a preparatory step in which pyruvate (a 3 carbon molecule) is converted to Acetyl CoA (a 2 carbon molecule). In the process energy is transferred to NADH. A carbon is released in the form of carbon dioxide (CO2)
    Acetyl CoA enters a cyclic pathway by joining a four carbon molecule. This newly formed molecule (Citric Acid –a six carbon molecule) now moves into a series of metabolic steps catalyzed by different enzymes. As it is rearranged energy as well as carbons (CO2) are released.  Ultimately it will join a new Acetyl CoA once again as the cyclic pathway continues.
    All the carbons in the molecule are ultimately turned into carbon dioxide as the cycle keeps turning. The released energy is captured by ADP (producing ATP) as well as NAD+ (producing NADH) and FADH (producing FADH2). In terms of numbers each glucose molecule forms 6 CO2, 2 ATP, 8 NADH and 2 FADH2 in the process. As you can see glucose is completely oxidized to carbon dioxide! A relatively small amount of ATP has been produced. In contrast a large number of NADH has been formed. Recall that NADH holds more energy than ATP molecules.
     As you are well aware cellular processes depend on the presence of ATP. The dilemma at this point is that so far very little ATP has been produced, The challenge is to convert the energy trapped in the NADH molecules to a usable form, i.e. to somehow transfer the energy to ATP molecules.

The Electron Transport Chain (ETC):
     The ETC also takes place in the mitochondria. A series of proteins are present in the inner mitochondrial membrane (the cristae). The electrons move through these proteins. Recall that membranes also serve as selective barriers in a cell.
     The goal of the process is to transfer the energy contained in NADH to ATP molecules. This is done in two steps:

• i) A proton gradient is built across the membrane. Such a gradient represents potential energy (an analogy could be water on a hillside)
• ii) As the protons move back through the membrane the potential energy is used to make ATP molecules (an analogy could be to allow the water on the hillside to fall and in the process capture the energy via a turbine).

Producing ATP:     As you know (based on your knowledge of diffusion) these molecules strive towards returning across the membrane. Unfortunately (or perhaps fortunately), the membrane does not allow these protons to cross the phospholipid bilayer. The membrane also contains numerous proteins fulfilling different cellular tasks. One of these proteins is ATP Synthase (also called ATPase). The protons can move across the membrane through the ATP synthase. As they do so the potential energy contained in the gradient is transferred to ATP (ATP forms from ADP and P), i.e. the energy from the NADH has now been transferred to ATP. Of course, the energy had its initial origin in the covalent bonds of a glucose molecule as it entered glycolysis.
     The newly formed ATP can now diffuse away from the mitochondria and perform cellular work in other parts of the cell. As it is used up it is split into ADP and P. These molecules now return to the mitochondria to “pick up” energy from the electron transport chain. The supply of ATP is continuously recycled.

1. Why do we breathe?
2. Is our "burning" of glucose an efficient process?
3. Understand how energy contained in chemical bonds can be transferred between molecules.
4. In this section you are introduced to NADH. This molecule has the ability to "carry" a large amount of energy. Remember how we referred to them in class as energy "shuttles".
5. Electron carriers and electron transport chains refer to processes that can transfer electrons. These electrons often end up on oxygen (thereby our great need for a constant supply of oxygen). In the process the energy contained in the electrons is transferred to other molecules (i.e. a different format that can be utilized).
6. How to make ATP? One way is to transfer part of the energy of a broken covalent bond of a "fuel" molecule directly to ADP+P forming ATP. This is called Substrate-level phosphorylation. The second way is to build a proton gradient across a membrane (remember our water on the roof discussion?). As the protons fall back across the membrane through an enzyme (ATPase) the call can make ATP (in our analogy: as the water falls from the roof we can run a turbine).
7. Know the three stages of cellular respiration: Glycolysis, the Krebs cycle and the electron transport chain (ETC from now on). The first two yield a very small amount of ATP while the last one yields a large amount of ATP.
8. Glycolysis: a biochemical pathway shared by  all cells on planet earth. Glucose is transformed to pyruvate in the cytoplasm. In the process a small amount of ATP is formed at the same time as some energy is transferred to NADH. The bulk of the energy available is still contained within the pyruvate molecules.  [Take a look at the whole process in this animation of glycolysis to get a feeling for the dynamic rearrangement of the molecules as glucose is transformed to pyruvate. No need to memorize the details of the pathway in the animation.]
9. As pyruvate enters the mitochondria in eukaryotic cells it is transformed into acetyl CoA. In the process some energy is transferred to NADH and a carbon is broken of the molecule. This is the first example of how CO2 is forming within the cell.
10. The Krebs cycle occurs inside the matrix of the mitochondria. Acetyl CoA is fed into a cyclic pathway. The molecules are rearranged as they cycle around in the pathway. [Look at the pathway in this animated presentation of the Krebs Cycle. Notice the rearrangement of the molecules (no need to memorize those details in our class). I included the link so you can get a feeling for what metabolism is all about (not to freak you out)]. In the process energy is transferred to ATP as well as to NADH (and FADH2 which is a similar molecule as NADH). Carbons are also released as CO2. At this point the glucose molecule has literally been broken down to carbon dioxide. Most of the energy has been released as heat but some energy has been transferred to ATP. The bulk of the energy has been transferred to NADH (remember our $100 analogy?). The goal now is to access this energy.
11. The energy contained in NADH is used to produce ATP. The energy rich electrons from NADH is transferred to a series of proteins in a membrane (the electron transport chain). The electrons move through these proteins. As they move the electrons lose energy and finally ends up on oxygen. The energy is used to move protons across the membrane to build a proton gradient. This is a form of potential energy (remember our "carry water up on the roof" analogy?). These protons strive to return to the other side of the membrane but they cannot pass the selective barrier of the membrane without "help". An enzyme called ATP synthase allows the protons to move through but take advantage of the steady movement of these protons to produce ATP (similar to our water turbine analogy in class). What would happen if oxygen was absent?
12. Different poisons can block the movement of electrons in the transport chain.
13. Study the diagram above as you try to connect the three processes discussed in this chapter into a view of cellular respiration. What is accomplished? What is needed for the process to occur? What is produced?
14. Fermentation: Understand the need for oxygen in cellular respiration. If it is absent the cell needs to replenish the precious NAD+ molecules to allow glycolysis to continue. (Recall our bus company analogy). The energy contained in NADH is "dumped" to produce another molecule so NAD+ can return to glycolysis. Thereby glycolysis can proceed with a low yield of ATP. The "other molecule" is often referred to as a fermentation product. Some examples are ethanol in yeast cells as well as lactic acid in muscle cells (heavy exercise).
15. Understand how the building blocks of all the macromolecules in food feed into different parts of the three pathways discussed. Cellular respiration is kind of a major metabolic "freeway", i.e. other expressways are linked to the main route.
16. In the same manner these molecules can be "pulled out" of the pathway (kind of like exits on the freeway) to provide building blocks for macromolecules in the anabolic pathways of the cell.
17. It is important to understand that the energy released and transferred in cellular respiration has its origin in the process of photosynthesis (and, of course, originally in the sun's energy).

• Biology Book - Harvesting Chemical Energy An excellent overview of cellular respiration and fermentation with lots of graphics. The page may take a while to load unless you have a fast connection, but it is definitely worth the wait.
• Biology Book - ATP and Biological Energy : An excellent overview of molecules that carry energy with lots of graphics.

Page created by: Peter Svensson Updated: February 28,  2007