Citric Acid Cycle
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Citric Acid Cycle

The reactions shown in the previous sections bring the fats through the steps of glycerol and fatty acids, through pyruvic acid and ultimately to acetyl CoA. At this point the acetyl CoA is combined with another compound to make citric acid. Citric acid goes through a number of steps (shown as the circle in the center of this diagram) and then recombines with acetyl CoA to make more citric acid which goes through the same cycle of steps again. This cycle is called the citric acid cycle. Carbon dioxide is formed at two of the steps in this process and hydrogen atoms are removed from the molecules along with their electrons at four of them.

66rxn04.JPG (4780 bytes)

 

As we examine the steps that are involved in the citric acid cycle, I would again like you to exercise your powers of observation and reasoning. I would like you to take a look at the citric acid cycle as it is presented in your textbook and also two other sources if you have some available to you. Those sources can be other chemistry or biology textbooks or whatever other sources you can find. We have a number of textbooks in the lab for you to use. If you have the time and inclination, do an internet search and see what you can find. After you've looked at the citric acid cycle, which is also known as the TCA cycle and the Krebs cycle, as it is represented in different sources, select the one that presents you with the clearest presentation of what happens at each step. Then copy down that particular version of the citric acid cycle and make notes about what happens at each step. For example, note that "there is a hydrolysis reaction" or that "hydrogen atoms and their electrons are being removed so it is an oxidation reaction".

Some additional instructions for doing that and also some space to copy down the version that you like best, are in Exercise 13 in your workbook. Take some time now to work on that. When you've done that, continue with the lesson and we'll resume our study of the citric acid cycle.

Overall Cycle

Okay, let's take a look at this and see how much of it you were able to figure out. This is the version of the citric acid cycle that I will use. A copy of it is in Example 14 in your workbook. Let's focus in on the citric acid as the starting point.

Citric acid cycle - structural formulas of all components, with citric acid labeled. [cacall1.jpg]

Getting Started

This compound is citric acid. It is quite common for textbooks to work with the ionic form of this compound, so the version that you have in front of you may very well refer to citrate rather than citric acid, and if that's the case, three hydrogens would have been removed and it would be an ionic compound.

Structure of citric acid. [cac00.jpg]

It's also quite common for textbooks to take these first two steps and treat them as one. They go from citric acid (or citrate) to isocitric acid (or isocitrate) and call it an isomerization reaction. But I'll break it down into two smaller steps.

Equation for steps 1 and 2 in the citric acid cycle. [cac0102a.jpg]

Step 1

Going from citric acid to the next compound, you should notice that we have the same network of carbon atoms. The change that occurs is that a double bond appears and an -OH and an -H disappear. So this first step is essentially a dehydration reaction.

Equation for the reaction in step 1 of the citric acid cycle. [cac01a.jpg]

Step 2

In the next step, the double bond disappears and an -OH and an -H reappear. So this step is an addition reaction. The water molecule has been added back in. But note that the -OH is in a different position than it was in citric acid. This compound is and isomer of citric acid (and thus it is named isocitric acid).

Equation for the reaction in step 2 of the citric acid cycle. [cac02a.jpg]

Again, if the version that you were working with showed the reaction going directly from the first compound to the third, you would classify that as an isomerization reaction. One in which the hydrogen and the hydroxyl groups change place.

cac0102a.jpg (6303 bytes)

Step 3

As we go to the next step in this process, the change is that two hydrogen atoms and their electrons removed. So this, of course, is an oxidation reaction.

Equation for the reaction in step 3 of the citric acid cycle. [cac03a.jpg]

Step 4

In the next step a carbon atom and two oxygen atoms disappear. A carbon dioxide molecule has been removed and this is called a decarboxylation reaction.

Equation for the reaction in step 4 of the citric acid cycle. [cac04a.jpg]

Step 5

The next step is a bit of a challenge. One carbon atom, two oxygen atoms and one hydrogen ato have been removed. That amounts to removing a CO2 molecule and one hydrogen with its electron. We have also added the coenzyme A. Now remember that the coenzyme A starts out with a hydrogen (as CoASH). That hydrogen is removed when coenzyme A attaches to this molecule. So we've actually released two hydrogen atoms with their electrons.

Equation for the reaction in step 5 of the citric acid cycle. [cac05a.jpg]

Step 6

In the next step we've removed the coenzyme A and we've put in an -OH. When the coenzyme A is set free it requires a hydrogen atom to go with it. So this is a hydrolysis reaction in which the -OH goes to the carbon and the -H goes to the coenzyme A.

Equation for the reaction in step 6 of the citric acid cycle. [cac06a.jpg]

Step 7

In this next a double bond appears in the middle of the molecule as a result of the removal of two hydrogen atoms along with their electrons. This is another oxidation reaction.

Equation for the reaction in step 7 of the citric acid cycle. [cac07a.jpg]

Step 8

In this step the double bond disappears and an H- and -OH have appeared, so this reaction is an addition of water.

Equation for the reaction in step 8 of the citric acid cycle. [cac08a.jpg]

Step 9

The next step involves removing two hydrogens and their electrons, so we have another oxidation reaction.

Equation for the reaction in step 9 of the citric acid cycle. [cac09a.jpg]

Step 10

Now we get to the step that involves regenerating the citric acid from this compound, which is called oxaloacetic acid. This step is somewhat involved, so I will describe it twice. First will be a deduction of what appears to happen based on the formulas of the chemicals involved. This is what I expect you may have been able to deduce. Following that will be a more complete description of how the reaction is accomplished.

In order to change the first molecule into the second, a number of things have to happen. First of all, we start with four carbon atoms and end with six. So we must somehow have to add two carbon atoms, along with other atoms. It would seem that could be accomplished by an addition reaction across the circled C=O double bond using an acetic acid molecule (in red). In these diagrams the orientation of one -COOH group (circled in green) has been changed, as has the orientation of the C=O group (circled in red) that becomes a C-OH group.

Equation for the reaction in step 10 of the citric acid cycle. [cac10a.jpg]

However, an acetic acid molecule, as such, is not involved in this reaction. Instead, those new atoms will come from the acetyl CoA that is generated from the breakdown of fat molecules. The diagram below gives a more complete description of what happens.

It will be easier to see how the new atoms fit in if we reorient the oxaloacetic acid molecule, moving the oxygen in the carbonyl group (C=O) from the right side of the molecule to the left and moving the lower -COOH up and to the right. Now the acetyl CoA can add across the C=O double bond (circled in red) and attach at the bottom of the molecule. The oxygen gains a hydrogen and the carbon gains the rest of the acetyl CoA.

Equation for the reaction in step 10 of the citric acid cycle with extra annotation. [cac10xa.jpg]

Then the coenzyme A is released by a hydrolysis reaction in which a water molecule provides an -OH to make the citric acid complete. It also provides the -H needed to complete the coenzyme A.

Note that what is shown as one step in the overall diagram really invoves several things happening in quick succession.

Overall

As you take a look at this overall process, keep in mind what you are and what you are not responsible for remembering about the citric acid cycle.

Equations for the reactions in the citric acid cycle. [cacall2.jpg]

You are not going to be held responsible for knowing what all the steps are in the citric acid cycle. Even so, you do need to know several things.

This process does involve many steps.
By looking at each step, you should be able to figure out what kind of reaction each one is.
You should know how the citric acid cycle fits into the overall scheme of things, specifically the overall process of oxidizing fats to form carbon dioxide and water.
You need to know that the fats are broken down into the glycerol and fatty acids.
Those are changed in turn to acetyl CoA which feeds into the citric acid cycle creating a citric acid molecule.
That citric acid molecule undergoes quite a number of changes and those changes involve giving off carbon dioxide at two points and giving off pairs of hydrogen atoms with electrons at four points.

All of this fits in with that earlier idea that when a fat molecule is oxidized to become carbon dioxide and water, there are a multitude of steps in the process. Each step is relatively simple but there are quite a number of them that have to occur in order to oxidize a fat molecule.

So far you have seen how carbon dioxide is formed, but you have not yet seen how the hydrogen is joined with oxygen to become water. That involves the electron transport system, which is the next section of this lesson.

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E-mail instructor: Sue Eggling

Clackamas Community College
2001, 2003 Clackamas Community College, Hal Bender