Cellular Respiration Tutorial
First, a disclaimer:  the cycles drawn below are quite simplified from the actual processes.  Many details have been left out.  Consult your book for a more detailed account of each step.  Use this tutorial as a starting point for understanding the pathways.

Let's list out what you DO need to know for cellular respiration:

    1.  The names of the intermediates in glycolysis and the Krebs cycle.  You DO NOT need to know ANY structures.
    2.  The steps which use ATP and NAD+.
    3.  The steps which produce ATP and NADH (and FADH2).
    4.  You should be able to (roughly) keep track of carbons throughout the reactions.  Just have a basic idea of what is
            going on.
    5.  Understand WHERE each of the steps occurs (cellular localization).
    6.  Understand the difference between substrate-level phosphorylation and oxidative phosphorylation.
    7.  Understand how much energy you get by just going through glycolysis, and how much more you get if you go through
            the Krebs cycle and the electron transport chain.
    8.  Understand the differences between fermentation and cellular respiration -- when each occurs and what energy results.
    9.  Understand the electron transport chain.  You should understand the steps in terms of potential energy and redox
            reactions.  Know how much ATP you can generate from NADH and from FADH2.
    10.  Know how the cell couples the H+ gradient with ATP synthesis using the electron transport chain and the ATP
            synthase.  Understand the terms chemiosmosis and proton-motive force.

1. Background:

We harvest energy from organic compounds by, ultimately, taking advantage of energy that is released in redox reactions.  Let's review redox reactions briefly:

Redox reactions are oxidation-reduction reactions.  Let's define these words:
        oxidation = the loss of electrons
        reduction = the gain of electrons
        you can remember this by the mnemonic:  OIL RIG (oxidation is losing, reduction is gaining)

        For example,     Na  +  Cl Na+  +  Cl-
        In this example, Na gives up its one valence electron to the highly electronegative chlorine, and as a result, has a
        positive charge.  Therefore, Na is oxidized to Na+.  Conversely, Cl gains an electron from Na.  Hence, Cl gets
       reduced to Cl-.

A couple more terms:
       oxidizing agent = the electron acceptor (i.e. the agent that oxidizes another substance)
       reducing agent = the electron donor (i.e. the agent that reduces another substance)
        In the above example, Cl is the oxidizing agent (since it accepts electrons), while Na is the reducing agent (since it
        donates electrons).

However, not ALL redox reactions involve the complete transfer of electrons.  Sometimes, electrons are just shifted within a covalent bond.

Let's think about energy as it relates to electrons.  We know that atoms that are very electronegative (like oxygen) pull strongly on electrons.  It is hard to pull an electron away from an atom of oxygen.  In the same way, it requires an investment of energy to KEEP an electron away from an electronegative atom.  Since it requires an input of energy to pull electrons away from an electronegative atom, we can see that energy will be released if we let electrons get closer to an electronegative atom.

Now let's apply this idea to covalent bonds.  Say we have a compound that has many C--H bonds.  We know that electrons are shared equally between C and H (these atoms do not have an electronegativity difference, the C--H bonds are nonpolar).  Say we transfer the H atoms from the C--H bond to oxygen, thereby forming O--H bonds.  We know that electrons are NOT shared equally between O and H (these atoms DO have an electronegativity difference, the O--H bonds are polar).  We know that since O is more electronegative than H, it pulls on the electrons that are shared between the two atoms more strongly than H does.  So the electrons move away from H (relative to their location in the C--H bond).

This is still a redox reaction!  Even though electrons don't get transferred COMPLETELY to O, there is still a PARTIAL transfer of electrons from H to O.  So in this example, O gets reduced when the H--O bonds form, and the C--H bonds are oxidized (if one thing gets reduced, the other must get oxidized).  In this type of redox reaction, energy is released because electrons are moving TOWARDS an electronegative atom (O), which is a more stable, more favorable orientation (think of how unstable systems move towards stability spontaneously, resulting in a -DG, the release of energy!).

This type of redox reaction forms the basis for how the cell derives energy from organic compounds in cellular respiration.

In respiration, the energy of redox reactions that occur during glycolysis and the Krebs cycle is captured by the electron shuttles NAD+ and FAD.  These molecules trap energy (and electrons) when they become reduced to NADH and FADH2.  The key in these transfers is that electrons lose very little of their potential energy when they are transferred from glucose (or other food molecules) to NAD+.   This is important because NADH simply shuttles the electrons (and their associated energy) from the Krebs cycle to the electron transport chain, where they are ultimately allowed to lose their potential energy through a series of steps, which results in the gradual release of energy and the eventual synthesis of ATP.  We'll cover all of this when we study the electron transport chain.
 

Let's go through respiration:  Please note that any time you see the red stars (***), I have provided an easy to memorize, easy to understand tip!  Here is the summary reaction for the breakdown of glucose:

                            C6H12O6 + 6 O26 CO2 + 6 H2O + energy (38 ATP = max. yield per glucose)
 

2.  Glycolysis:
 
 

Okay, let's break this down so that it's more manageable.  There are 9 steps (9 green arrows).  These can be divided into the "Energy-Investment Phase" and the "Energy-Payoff Phase" (note the dotted line in the diagram above, with the red arrow indicating energy investment and the green arrow indicating energy payoff).  In the energy-investment phase, we USE a total of TWO molecules of ATP to drive reactions forward.

*** How can we remember which reactions USE ATP???  Note that the products of both reactions (glucose 6-phosphate and fructose 1,6-bisphosphate) both have one MORE phosphate group attached to them than the reactants (glucose and fructose 6-phosphate, respectively).  We know that ATP transfers phosphate groups to molecules, so this makes sense.***

Now the top part of the pathway doesn't look quite as complicated.  Note that the rule we just learned for when ATPs get USED can also be applied to when they are GENERATED in the "Energy-Payoff Phase" of glycolysis:

*** How can we remember which reactions GENERATE ATP???  Note that the products of both reactions (3-phosphoglycerate and pyruvate) both have one LESS phosphate group attached to them than the reactants (1,3-bisphosphoglycerate and phosphoenolpyruvate, respectively).  We know that the regeneration of ATP from ADP requires the addition of phosphate groups to ADP, so this makes sense.*** We call this process of ATP generation by the direct transfer of a phosphate group of a glycolytic intermediate to ADP substrate level phosphorylation.

We can also keep track of the carbons easily (they are indicated in the figure above):  Glucose is a 6-carbon compound.  It gets broken down to two 3-carbon compounds (dihydroxyacetone phosphate and glyceraldehyde phosphate).  Only glyceraldehyde phosphate can continue down the path, so the dihydroxyacetone phosphate gets converted to glyceraldehyde phosphate.  So, for every one glucose molecule, we get TWO glyceraldehyde phosphate molecules.  Now, add the carbons to make sure if this is correct:  glucose (6 C) = 2 x glyceraldehyde phosphate (3 C).

There are no additional losses of carbon during glycolysis.  We end up with the 3 C pivotal molecule, pyruvate.

Let's do a check of how much we've spent and what we've gained:
           1 molecule of glucose + 2 ATP + 2 NAD + 2 ADP yielded 2 molecules of pyruvate + 4 ATP + 2 NADH + 2 H+
      NET: 1 molecule of glucose + 2 NAD+ + 2 ADP yielded 2 molecules of pyruvate + 2 ATP + 2 NADH + 2 H+

This ENTIRE process of glycolysis is carried out in the CYTOPLASM.   Then, pyruvate gets transported into the mitochondrion and immediately, CO2 is stripped from the molecule!  This means that our 3 C pyruvate loses 1 C, and we're left with a 2 C molecule, which is called acetyl CoA.  As we are generating acetyl CoA, we also reduce NAD+ to NADH + H+.

So, in the conversion of pyruvate to acetyl CoA:
                pyruvate:  1.  loses a molecule of carbon dioxide
                                2.  reduces NAD+ to NADH + H+
                                3.  gains a coenzyme A (CoA) group which makes it unstable and reactive
        1 molecule of pyruvate + 1 NAD+ + CoA yielded 1 molecule of acetyl CoA  + 1 CO2 + 1 NADH + 1 H+
        Remember that for every molecule of glucose, there are TWO pyruvates produced, so this yield should be doubled
        when taking the entire glycolytic pathway into account.

Acetyl CoA enters the Krebs cycle.  Let's study this in detail:

3.  Krebs cycle: 
Okay, let's break this down so that it's more manageable.

First, notice why this is a "cycle".   We start with oxaloacetate (OAA) and add the incoming acetyl CoA (derived from the pyruvate endproduct of glycolysis) to form citrate.  We proceed through 7 steps, and eventually regenerate OAA.  This OAA once again joins with acetyl CoA, and we begin the process once again.  Hence, we have a cycle.  You may also have heard the Krebs cycle called the Citric Acid Cycle -- now the reason should be obvious!  By the way, Hans Krebs was the German-British scientist who, in the 1930's, contributed significantly to the understanding of this cycle.

Remember that the cycle turns TWICE for each glucose molecule that enters glycolysis.   This is because each molecule of glucose (6 carbon) is split into two molecules of pyruvate (3 carbon).  Each molecule of pyruvate, in turn, is converted to acetyl CoA, which enters the Krebs cycle.

We can also keep track of the carbons easily (they are indicated in the figure above):  Acetyl CoA is a 2 carbon compound (remember that it is generated when 1 carbon dioxide molecule is removed from pyruvate).  It enters the Krebs cycle by combining with oxaloacetate (4 carbon) to form citrate (6 carbon).  Now, we know that we have to get back to OAA in order for the cycle to repeat itself.  So, we must have to LOSE 2 carbons along the way as we convert citrate (6 carbon) back to OAA (4 carbon).  Notice that we lose those 2 carbons in the form of two molecules of carbon dioxide that are given off when isocitrate is converted to a-ketoglutarate, and when a-ketoglutarate is converted to succinyl CoA.  You know that when we EXHALE, we breathe out carbon dioxide.  This is where it comes from!!!!

The Krebs cycle occurs entirely in the matrix of the mitochondrion (inside the inner membrane).

Let's do a check of how much we've spent and what we've gained:
         1 molecule of acetyl CoA + 3 NAD + 1 FAD + 1 ADP yielded 2 CO2 + 1 ATP + 1 FADH2+ 3 NADH + 3 H+

You'll notice that we have now only got ATP, FADH2, and NADH as products (CO2 is exhaled).  The organic glucose was broken down to 2 molecules of pyruvate in glycolysis.  Pyruvate was converted to acetyl CoA (with the net loss of ONE carbon in the form of carbon dioxide per pyruvate, a total of TWO carbon dioxides per glucose molecule), and acetyl CoA entered the Krebs cycle.  During the Krebs cycle, we lost 2 carbons in the form of carbon dioxide, which is equivalent to the loss of the original acetyl CoA that we invested (so for each molecule of glucose, the cycle turns twice and we lose a total of 4 carbons).  This means that we have lost, by the end of glycolysis and the Krebs cycle, a total of 6 carbons -- the amount we put in when we started with glucose.  So, now we're ready to harvest the energy stored in FADH2 and NADH!
 

4.  Electron Transport Chain:

The electron transport chain is located in the inner membrane of the mitochondrion.  There are thousands of copies of the electron transport chain per mitochondrion.  The key is that one side of the chain faces the matrix and the other side faces the intermembrane space.

Remember that we have generated some molecules of ATP already (through a process called substrate-level phosphorylation, whereby phosphate groups are transferred directly from some intermediate in glycolysis or the Krebs cycle to ADP to form ATP!).  We have also generated NADH and FADH2.  Now, we need to harvest the energy that is stored in the electrons of NADH and FADH2, the reduced forms of NAD+ and FAD.  We do this through a series of redox reactions that are carried out along the electron transport chain.  Remember our discussion at the beginning of this tutorial:  as electrons move from a less electronegative atom towards a more electronegative atom (favorable) energy is released.

Most of the components along the electron transport chain are proteins.  These proteins have nonprotein groups attached to them (called prosthetic groups) that can be reduced as electrons are passed to them, and can be oxidized as electrons are removed from them.  The electrons "fall" down the electron transport chain because it is energetically favorable for them to do so!  Why is it favorable for the electrons to fall down the chain?  Well, from our previous discussion, you might infer that each successive component of the electron transport chain is slightly MORE electronegative than the component before it.  And we know that electrons like to be close to electronegative atoms!  So, electrons move down the transport chain because they are successively moving closer and closer to more and more electronegative atoms.  The final carrier in the electron transport chain is oxygen.  This makes sense since oxygen is an EXTREMELY electronegative atom.

Electrons start out bound to NADH.  Remember that NADH retains the potential energy that electrons had when they were in food.  When NADH encounters the first component of the electron transport chain (FMN), it gives its electrons to FMN.  In other words, NADH is an electron donor (it gets oxidized back to NAD+) and FMN accepts electrons (it gets reduced).  The electrons are then passed from FMN to an iron-sulfur containing protein (i.e. FMN gets oxidized and the Fe-S protein gets reduced).  And so on... all the way down the electron transport chain until the final carrier (cytochrome a3) becomes re-oxidized after it passes a pair of electrons to oxygen (which gets reduced!).  FADH2 acts like NADH, except that its electrons have less energy associated with them than the electrons of NADH.  Therefore, FADH2 dumps its electrons further down the electron transport chain (they don't have as far to fall to reach the bottom).

So now all of the electrons have passed successively lost energy as they have fallen down the electron transport chain, but how does this yield energy???  The answer is chemiosmosis.

What is chemiosmosis and how does it work?
You already know that electrons "fall" down the electron transport chain because it is energetically favorable.  As it turns out, when electrons are passed to some members of the electron transport chain, those specific members of the electron transport chain not only pass the electron on to the next component in the chain, but they also pick up a H+ from the solution of the mitochondrial matrix and pump it into the intermembrane space!  In this way, as electrons fall down the electron transport chain, protons get pumped from the matrix to the intermembrane space, thereby establishing a concentration GRADIENT.
We know that substances like to move from where they're more concentrated to where they're less concentrated (they move down their concentration gradients).  So the H+ that build up in the intermembrane space during the transport of electrons down the electron transport chain want to come back into the matrix to re-establish equilibrium.  However, we also know that lipid bilayers are not permeable to ions!  It takes energy to continue to push H+ into the intermembrane space because this movement represents a movement AGAINST the concentration gradient.  The energy to pump the H+ from the matrix to the intermembrane space comes from the passage of electrons down the electron transport chain.
IN OTHER WORDS, the cell couples the exergonic "fall" of electrons down the electron transport chain with the ENDERGONIC pumping of H+ from the matrix to the intermembrane space against their concentration gradient!
Once the cell has established a H+ concentration gradient (called a proton-motive force), it allows the H+ to flow back into the mitochondrial matrix through specialized proteins called ATP synthases.  The flow of H+ back into the mitochondrial matrix (DOWN their concentration gradient) is EXERGONIC.  The ATP synthase captures the energy being released from this flow of H+ and couples it with the synthesis of ATP!.  This process of coupling the redox reactions of electron transport to ATP synthesis via the establishment of a H+ gradient is called chemiosmosis.

Let's see what all of this LOOKS like:

5.  Summary of Energy Release:

                glycolysis (net):    2 ATP + 2 NADH
               conversion of pyruvate to acetyl CoA: 1 NADH for each pyruvate = 2 NADH
               Krebs cycle:  1 ATP + 1 FADH2+ 3 NADH times two = 2 ATP 2 FADH2+ 6 NADH

                TOTAL = 4 ATP (by substrate level phosphorylation) 2 FADH2+ 10 NADH

               1 NADH has enough energy stored to make 3 ATP by oxidative phosphorylation
                1 FADH2 has enough energy stored to make 2 ATP by oxidative phosphorylation

               So, the total amount of ATP possible = 38 ATP