Daily Newsletter
October 3, 2012 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
In your own words describe the citric acid cycle.Link to Forum
"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."
ReplyDeleteSo I just want to ask, is it good to take CoQ10 to lower my cholesterol? My friend also told me that when I take cholesterol lowering drug, I must also take CoQ10, do you know why?
Talking with your physician or pharmacist is your best option. One of my areas is molecular biology, but I don't keep up with all of the journals in medicine. I have read where there is clinical evidence of CoQ10 helping with Huntington's Disease, but most of the commonly reported beneficial effects have not been clinically supported.
ReplyDeleteYour physician and pharmacist probably read more of the medical and pharmacological journals, and may have more current information on research directions with CoQ10.
As for your question of CoQ10 does not lower cholesterol. CoQ10 shares metabolic pathways used in making cholesterol. Some cholesterol lowering medications (statins, like Lipotor) have been shown to lower blood levels of CoQ10. I suspect the reasoning for taking CoQ10 is to supplement a reduction in the amount of CoQ10 your body can produce naturally while taking statins. Your best option though is still to consult with your doctor or pharmacist. Always check to see if there are contraindications with any other drug your taking.