Citric Acid Cycle II 
Citric Acid Cycle II
by OSU
Video Lecture 2 of 25
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Date Added: February 15, 2015

Lecture Description

1. The citric acid cycle consists of two main parts - release of CO2 (first part) and conversion to oxaloacetate (second part). You are responsible for the structures of molecules in the citric acid cycle and the names of the enzymes.

2. In the "first" reaction of the citric acid cycle, citrate synthase catalyzes the joining of the acetyl group from acetyl-CoA to oxaloacetate to make citrate. This reaction is VERY energetically favorable, due to breaking of the thioester bond in acetyl-CoA. The energetically favorable reaction helps to "pull" the relatively unfavorable reaction preceding it.

3. Aconitase catalyzes the rearrangement of citrate to isocitrate. For your information - Aconitase is inhibited by fluorocitrate. Fluoroacetate is a poison that can be used by citrate synthase to make fluorocitrate.

4. The first decarboxylation of the citric acid cycle is catalyzed by isocitrate dehydrogenase and the reaction is strongly favored to the right. The products of this reaction are NADH and alpha ketoglutarate.

5. Alpha ketoglutarate is an important intermediate for its involvement in anaplerotic reactions related to transamination (we'll talk about these later). The mechanism of the enzyme acting on alpha ketoglutarate (alpha ketoglutarate dehydrogenase complex) is virtually identical to the mechanism of action of the pyruvate dehydrogenase complex and involves all of the same coenzymes. The products of this reaction are succinyl-CoA and NADH

6. The only substrate level phosphorylation in the citric acid cycle is catalyzed by succinyl-CoA synthetase. The products of this reaction in the citric acid cycle are GTP and succinate. Note that the enzyme is named for the reverse reaction.

7. Succinate dehydrogenase contains a covalently-linked FAD electron carrier. The Delta G zero prime of zero allows the reaction to be readily reversed to produce succinate, when needed. The products of this reaction in the forward direction of the citric acid cycle are FADH2 and fumarate (trans double bond). This reaction is similar to the first oxidation reaction for a fatty acid.

8. Addition of water to fumarate (catalyzed by fumarase) yields L-malate.

9. Oxidation of L-malate by malate dehydrogenase yields NADH and oxaloacetate. This reaction is a rare oxidation reaction that is energetically unfavorable. Conversion of malate to oxaloacetate is the only energy "bump" to be gotten over in the citric acid cycle and that is readily accomplished thanks to the 'pulling' of the citrate synthase reaction, which keeps oxaloacetate concentrations low.

10. The citric acid cycle can be regulated allosterically in several places, but the most important regulation of the cycle is probably the amount of NAD+ and FAD that is available. NAD+ (and FAD) is essential for the cycle to operate and it is essential for the pyruvate dehydrogenase complex reaction to occur. This relates to metabolic control, as we shall see in discussions later of electron transport and oxidative phosphorylation.

11. When all of the NADHs and FADH2s of the citric acid cycle are converted to ATP, the cycle yields 30- 38 ATPs per molecule of glucose (depending on how you count them - we'll talk about this later), compared to 2 for glycolysis (under anaerobic conditions). The citric acid cycle is thus an incredibly efficient producer of energy for the cell.

12. Many factors combine to regulate metabolism through the citric acid cycle. All of these ultimately come down to energy needs. Most are manifested through the availability or lack of NAD+. When NAD+ is lacking (high NADH levels), the cycle will be inhibited. When NAD+ levels are high (low NADH levels), the cycle is favored. Oxygen is a limiting reagent needed to keep the citric acid cycle turning. This is because oxygen is required ultimately for the conversion of NADH back to NAD+. Remember that NAD+ is required for three reactions of the citric acid cycle. If any one of these reactions is stopped, the cycle grinds to a halt. While glycolysis can use fermentation to get around conditions lacking oxygen, the citric acid cycle cannot.

Course Index

Course Description

This course in general biochemistry is intended to integrate information about metabolic pathways with respiration (respiratory control) and initiate the student into a microscopic world where blueprints are made of deoxyribonucleic acids, factories operate using enzymes, and the exchange rate is in ATPs rather than Yens or Euros. Beyond explaining terms, and iterating reactions and metabolic pathways, this course strives to establish that the same principles that govern the behavior of the world around us also govern the transactions inside this microscopic world of the living cell. And by studying and applying these principles, we begin to understand cellular and bodily processes that include sensory mechanisms.

Topics include:
1. Lipids, Membranes and Transport
2. Electron Transport, Oxidative Phosphorylation and Mitochondrial 3. Transport Systems
3. Lipid Metabolism
4. Nucleotide Metabolism
5. DNA Replication
6. Transcription
7. Translation


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