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Chapter 6: Cellular Respiration - Krebs Cycle, Electron Transport, and Chemiosmosis.

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The Chemical Basis of Cell Respiration

Web Lecture

Cellular Respiration II

In the previous lecture, we saw that the end of the glycolysis process, a single glucose has become two pyruvate molecules, with a net gain of two ATP molecules in the cell's energy store.

To better visualize what is happening, take a look at →John Kyrk's Glycolysis simulation.
  1. Examine the way that glucose can morph into fructose and back.
  2. Note the instructions for interacting with and controlling the rate of changes. Then click on the "continue" arrow on the left side of the screen.
  3. Step through the animation of changes until you reach the end and have pyruvate.
  4. Note the changing names of the enzymes at each step in the bottom left of the page. Why is a different enzyme required?
  5. Under what conditions will pyruvate enter a process to produce lactic acid?
  6. Click on the "up" arrow to see how lactic acid forms. How many steps are involved?
  7. click on the right arrow next to "ethanol" to see how ethanol forms from pyruvate. What happens?
  8. Leave the window'll need to go on to the Krebs cycle shortly.

The energy to create the ATP comes from breaking the bonds in the original glucose molecule, and is stored in the phosphate bond. The NAD+ ion also gains energy (in the form of two electrons) along with the H+ which transforms it into NADH. Although many of the reactions in the respiration process involve ATP←→ADP conversions, the real energy gain comes from the high-energy electrons transferred from the glucose to the NAD+.

Acetyl CoA production: From pyruvate to Acetyl CoA

The next three phases of the respiration activity occur in a mitochondrion, one of those kidney-bean shaped organelles filled with folded membranes. In the first of these phases, the pyruvate from the glycolysis phase is converted to a new compound, acetyl coenzyme A. The oxidative decarboxylation which accomplishes this just means that the pyruvate loses a carboxyl group (COOH). The H is picked up by an NAD+ molecule, and CO2 is formed from the rest of the carboxyl group. The remainder from the pyruvate combines with coenzyme A to form acetyl coenzyme A. The process produces another NADH molecule to the product pool.

This is a rather interesting development! We break down the pyruvate into smaller and smaller bits, until we are left with 2-carbon fragments. The coenzyme is a taxi-cab. It will carry the acetyl group, all that remains of the pyruvate complex, to an oxaloacetate compound. Once it has discharged its "passenger", the coA molecule will find another pyruvate to break up.

Citric Acid Cycle: From Acetyl CoA to lots of NADH

Click on the option to continue with the Krebs cycle (if you have closed the window, here is →John Kyrk's Kreb's Cycle simulation).
  1. Step through the animation of changes: where do molecules or atoms come into the cycle? Where are they give off?
  2. Watch the energy meter.

We've now entered the sequence of reaction steps called the Krebs cycle. Now you need to keep track of the carbons. The first molecule formed, citrate, has 6 carbons; in subsequent stages of the cycle it loses carbon atoms to carbon dioxide, and hydrogens to NAD+ and FAD. It also loses water to the mitochondria interior, and phosphate to a carrier molecule GDP, which in turn loses it almost immediate to an ADP, forming ATP. The final product, oxaloacetate, has only 4 carbons. This process produces a lot of NADH: 6 molecules from 2 pyruvate molecules, as well as two FADH2 molecules, each of which is capable of absorbing electrons but at a lower energy level than NADH.

As with the glycolysis phase, each step of this cycle has its own enzyme. All the steps are either rearrangment steps, or steps to split off some small group of atoms. Ultimately, we wind up with exactly the same oxaloacetate molecule that we started with! But in the meantime, we've released not only some simple molecules of water and CO2, we've also produces two different "energy carrying" molecules, the NADH and FADH2 groups. These have some high-energy electrons in their bonds, and will be happy to get rid of the disruptive particles by dumping them into a nearby membrane.

Electrical Transport and Chemiosmosis: From NADH to energy stored in ATP

So far, most of the processes have involved phosphate transfers, or the absorption of H+ and 2 electrons by NADH or FADH, and the loss of water and carbon dioxide. The final stage of cellular respiration is very different, and produces the most energy.

Go back to the basic picture of an atom, from chapter 2. Each atom has some number of electrons in different orbits, and to stay in a given orbit requires a certain specific amount of energy. The electron must either gain energy or give up energy to change orbits.

In the electron transport model, electrons move from a higher energy orbit on one molecule to a lower energy orbit on the next. The energy given up in this transfer is used to add a phosphate ion to ADP, making it ATP. NADH loses electrons from a very high energy level, so these electrons go through a three-step cascade process, losing enough energy at each step to make an ATP molecule. FADH2 loses electrons from a lower level, so its cascade process produces only 2 ATP.

The actual molecules which receive the electrons are complexes embedded in the internal membrane of the mitochondrion. As the electrons cascade, protons (H+) are released to the space between the matrix or interior membrane and the outer membrane of the mitochondrion. The charged protons are allowed back into the matrix (where diffusion would like to push them) only through another protein complex which stores the energy released by the proton "falling down the concentration gradient" in another ATP.

Now look at →John Kyrk's Kreb's Mitochondrion chemiosmosis simulation).
  1. Step through the animation.
  2. Note the structure of the mitochondrion, especially the lipid bilayer membrane.
  3. What are some of the differences between the three electron carriers?
  4. What happens when the electrons pass from NADH to the flavin carrier?
  5. What is ubiquinone? What does it do?
  6. What is cytochrome C? What does it do?
  7. What happens to the "spent" electrons?
  8. The simulation will run for several cycles, accumulating H+ and electrons, release the electrons to oxygen.
  9. What is ATP synthase? What does it do?

The overall gain in energy is 36-38 ATP from one glucose molecule. Since each ATP phosphate bond releases 7.3 kilocalories per mole, the total energy released and captured in this process is about 263 kcal/mole. This is just under 40% of the energy represented by all the chemical bonds in the original glucose molecule, so the entire process is pretty efficient.

Cellular respiration does not have to start with glucose. Proteins break down into acids which can be further catalyzed to provide pyruvate, acetal CoA, or the 5-carbon compound of the citric acid cycle. Fatty acids break down into the glycerols which make up the PGAL precursors of pyruvate, or into acetyl CoA. Each of these products then enters the aerobic respiration process at the point where it is needed as a reactant.

Anaerobic energy production

If there isn't enough ADP to absorb the phosphates produced in cellular respiration, glucose breakdown stops, electron flow stops, and the citric acid cycle collapses. The cell has to find other ways to produce energy. This it does through anaerobic reactions, so-called because they do not burn oxygen. Instead, some cells (like those in yeasts) break down pyruvate to form ethyl alcohol, while others (in fungi and bacteria) modify the pyruvate with hydrogen ions to make lactate (sours milk). Neither of these is as efficient a way to store energy for the cell; energy remains trapped in the products and can be released by other means, such as burning the alcohol.


So far, we've discussed only catabolic processes, which break complex molecules into their component groups. The cell also performs anabolic processes, through which it syntheses the proteins, nucleic acids, lipids, and polysaccharides it cannot obtain from its environment. As with the catabolic processes, each step is catalyzed by a specific enzyme. The rate at which the catabolic processes and anabolic processes occur can be separately controlled.