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Aerobic Respiration

So far, we have managed to break down glucose to two molecules of pyruvate, but have gained 2NADH and only 2ATP.  This is a rather pathetic return on an investment that cost approximately 54 ATP when plants synthesized glucose in the Calvin cycle.  We have to be able to extract more energy from glucose than that.  We can, if we use mitochondria and oxygen.  When I teach this class in person I always ask students to tell me why they need oxygen.  They know that oxygen is necessary for life and that without it cells and organisms die.  They are aware that there are complicated organs and a respiratory and circulatory system (heart, lungs, blood vessels, blood) in us to assure a constant oxygen supply to our cells, but no one ever knows exactly what cells do with that oxygen.  If you are as stymied by this question as my other students always have been, have no fear.   The answer is coming soon.

Before we see the function of oxygen in the aerobic process of cellular respiration, we need to follow our pyruvate into the mitochondrion where it will be completely broken down into carbon dioxide.  For simplicity, we will look at only one molecule of pyruvate, but you must remember that for each glucose molecule that enters glycolysis two pyruvate molecules are produced.  Let's examine the process in stages and then we will look at the whole thing together.

The first step in the process is to convert the pyruvate into a form that can enter the citric acid (CA) cycle.  I like to refer to this  as the "bridge stage" between glycolysis and the CA cycle.  Note that pyruvate enters the mitochondrion and one carbon is removed as carbon dioxide.  Some of the energy released by this reaction is used to reduce NAD to NADH.  A molecule of coenzyme A (CoA) attaches to the two carbon molecule that remains and activates it.  The result is acetyl-CoA, an activated form of acetic acid (vinegar).  It is acetyl-CoA that enters the citric acid cycle.  So, of the three carbons that entered the mitochondrion in each pyruvate, only two are left to enter the CA cycle.  The process of breaking down glucose to carbon dioxide has begun in earnest.   Now let's play our little in-out game and summarize what happened. 


Pyruvate CO2 (as waste)
CoA acetyl-CoA

Citric acid (CA) cycle

Now we are ready to enter the CA cycle.  As I have done before, I am going to greatly simplify a process that is in reality quite complex.  What I am going to show you is the bare bones of the cycle and we will concentrate on its purpose.  Remember, we are trying to generate ATP by breaking the bonds in glucose and capturing as much as possible of the energy stored in that molecule.  The CA cycle will produce very little ATP directly, but will generate many molecules of reduced coenzymes NAD and FAD as NADH and FADH2.  These will be of critical importance.

We will continue our story now by starting with the bridge and the entrance of acetyl-CoA into the citric acid cycle.  The first thing that happens is that the 2 carbons from acetyl-CoA combine with a four carbon compound present in the cycle.  Citric acid is formed using the six carbons.

Now let's go all around the cycle until we get back to the four carbon compound with which we started.  (It is named oxaloacetate, by the way, but I won't ask you to memorize that mouthful.)

  1. 2 NAD are reduced to 2 NADH and two carbons are removed and leave as 2 CO2.  Let's do a carbon count now.  There were 6 carbons in glucose.  Glycolysis resulted in two pyruvates, each with 3 carbons.  Each pyruvate entered the mitochondrion and lost 1 carbon in the "bridge" and 2 more in the CA cycle.  The glucose has been completely oxidized to carbon dioxide.
  2. There is a substrate-level phosphorylation of ADP to ATP (phosphorylation without chemiosmosis). 
  3. The cycle continues with reactions that will resynthesize the original 4 carbon oxaloacetate.  FAD is reduced to FADH2.   Another NAD is reduced to NADH.

Now I have combined all this into one animation.  It jumps between sections because each one was created separately and they didn't combine smoothly.  Some day, with more time, I'll try to fix this for you, but for now ignore the jumps and think of all this as happening continuously.  You can replay all of this as often as necessary until it makes sense.   Don't forget that there are 2 pyruvate from each glucose molecule, so the complete oxidation of glucose requires 2 turns of the CA cycle.

Each cycle takes only a fraction of a second (substantially less time than it takes to learn about it).  It is important to realize that there are hundreds of CA cycles operating simultaneously in a single mitochondrion and there can be more than a hundred mitochondria in an active cell.  Since an organism like you contains billions of cells, this process is happening countless times in you while you are sitting and reading this.  If the citric acid cycles in you stopped functioning, you would die!  But why?  We started this process to learn how cells obtain the ATP necessary to do   work. So far each glucose molecule has provided us with 2ATP from glycolysis and 2 more from the CA cycle (1 ATP from each cycle).  This is still a far cry from the approximately 54 ATP it took plants to synthesize glucose.  Before we learn where more ATP comes from, lets look at the ins and outs of the CA cycle.  In the following table the yellow cells represent the "bridge" stage and the blue cells, the actual CA cycle.


1 Pyruvate 1 CO2 (as waste)
CoA acetyl-CoA
1 acetyl-CoA 2 CO2 (as waste)

It's now time for some addition.  If we look at the table, we see that for each pyruvate entering the mitochondrion we obtain 4 NADH, 1 FAD2 , 1 ATP and 3 CO2 (as waste).  The bulk of the ATP obtained   from aerobic respiration comes from the reduced coenzymes, NADH and FADH2.   Continue on to the next page for the rest of the story.

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copyright June B. Steinberg, 2000