Daily Newsletter

October 2, 2013 Citric Acid Cycle

In organisms that experience cellular respiration (more about this tomorrow), pyruvate will be further reduced (extracting electrons and hydrogen). In eukaryotic cells, the pyruvate will be passed to the mitochondria. So, the following reactions will take place in the mitochondria. Where will they take place in prokaryotes?

At the end of glycolysis, we had two pyruvates. We are going to look at what happens if glucose is completely catabolized for energy. Remember though that cells have to determine moment by moment whether they need energy or resources.

The pyruvates produced by glycolysis will enter the mitochondria. They will be acted upon by the Pyruvate Dehydrogenase Complex.

The name implies that there is a great deal going on, and that there is more than one enzyme involved. The reaction, as shown on the right, involves some dramatic changes to the substrate. Notice that 2 CO₂ (carbon dioxide) will be released. Thus this is a decarboxylation reaction (de- = to remove, carboxylation = addition of carboxyl group, ∴ a decarboxylation is the removal of a carboxyl group). Further, you will notice that NAD⁺is reduced to NADH + H⁺. Any time you see this reaction, you know that the substrate was oxidized. So a redox reaction has occurred. CRITCAL NOTE: Any time you see an electron carrier reduced, you know that the substrate has been oxidized.

One other reaction has taken place. A structure known as Coenzyme A has been added.
Coenzyme A (CoA) is synthesized from vitamin B₅ (Pantothenate), and is one of the common coenzymes found in cells. CoA acts as a carrier molecule. In the case of Acetyl CoA, the acetyl group is incredibly important. Acetylation (the addition of acetyl group to a molecule) is a common biochemical reaction, and like any critical function must be regulation. That is where the CoA comes into play. It helps to insure that the acetyle group is added to the correct compound. NOTE: the acetyl group has one unpaired electron, so it is reactive. Enzymes used in acetylation are built so that their active site recognizes and requires CoA. For our purposes today, the CoA will help direct the acetyl group to the Citric Acid Cycle.

The Citric Acid Cycle is a biochemical pathway in which the the initial substrate is regenerated by the last step. The purpose of the citric acid cycle is to extract reducing potential (electrons & hydrogens). This will complete what is called the complete oxidation and decarboxylation of glucose. This reaction has a few alternative names: Tricarboxylic Acid Cycle (TCA), Kreb's Cycle, and Szent-Györgyi–Krebs cycle. The most common alternative use will be Kreb's Cycle or the abbreviation TCA (which is used extensively). Below is a diagram of the TCA cycle.

In the first reaction, Oxaloacetate is combined with Acetyl-CoA by the enzyme Citrate Synthase. Oxaloacetate is a highly reduced four carbon carboxylic acid. The addition of the Acetyl-CoA makes creates a 6-carbon citrate (citric acid) molecule. From here, chemical reactions take place that will further reduce and decarboxylate the molecule, resulting ultimately in a new molecule of Oxaloacetate. So, we have a cycle.

In studying glycolysis, you saw why certain reactions took place. Today we have already looked at decarboxylation and the significance of seeing an electron carrier reduced. Today, I want you to look at this reaction and start figuring out what is happening. There are a few hints I'll leave you with:

The enzyme Aconitase and the intermediate cis-Aconitate are recent additions to the cycle. They represent an intermediate that forms in the conversion of Citrate to Isocitrate.
Dehydrogenase means removal of hydrogen. Removal of hydrogen also implies removal of electrons.
In the conversion of Succinyl-CoA to Succinate, you have a substrate level phosphorylation (this time of GDP). It looks strange, but it involves the operation of the enzyme.
In the oxidation of Succinate to Fumarate, you see the reduction of Q to QH₂. Q represents Quinone (we will see this tomorrow). In many text books, it is represented as the electron carrier FAD. Regardless of the representation, this is a weaker redox reaction than we normally see. Less energy is being harvested in this step than in the steps where NAD⁺ is reduced. For now remember that it is a weaker energy harvesting.
In the conversion of Fumarate to Malate, water is added. Why? When you want to clean a sponge, don't you add water and wring out the sponge? While not the same thing here, the mental image of wringing to molecule to get out all available energy is good. The addition of water means we are also adding hydrogens and electrons. This is not a reduction, but the reaction will allow us to do one last energy harvesting.

Daily Challenge

Read the following article from Molecular Cell (Note: This is an introduction to an issue where there are articles on the evolution of central metabolism. The author is providing initial remarks to set the stage. This is not a research article.)

David A. Fell, Evolution of Central Carbon Metabolism,

Molecular Cell, Volume 39, Issue 5, 10 September 2010, Pages 663-664, ISSN 1097-2765,

http://dx.doi.org/10.1016/j.molcel.2010.08.034.(http://www.sciencedirect.com/science/article/pii/S1097276510006702)

There will be words that you do not know; mark them to look up after you finish the article the first time (it is brief). You will need to review the article a few times. Consider what is being said in this article regarding the evolution of central metabolism.

For your post, consider the following questions:
Why is glucose the most widely utilized sugar? (We will see that the Calvin cycle in plants produces glucose).
Why not some other carbohydrate?
Could one of the intermediates, say Glyceraldehyde 3-P or Pyruvate been an initial carbon source?

Write up a discussion of the evolution of central metabolism. (You are only dealing with carbon acquisition. We will discuss energy next week).