8.5
The Citric Acid Cycle
The citric acid cycle, also known as the Krebs cycle or TCA cycle, consists of several energy-generating reactions that yield one ATP molecule, three…
The citric acid cycle is a closed loop of reactions that occur in the mitochondrial matrix, including redox, dehydration, hydration, and decarboxylation reactions.
It's name is derived from the intermediate compound citric acid as the steps were first described by Hans Krebs, this aerobic pathway is also known as the Krebs cycle, which over a series of eight enzymatic steps, is critical in glucose catabolism.
To begin, acetyl CoA, the resulting compound from pyruvate oxidation donates its acetal group to a four carbon molecule oxaloacetate forming a six carbon intermediate citrate. While it's CoA group is bound to a self hydro group and diffused away to eventually combine with another acetal group. A water molecule is then removed and replaced, transforming citrate into its isomer isocitrate. The molecule is then oxidized, reducing NAD+ to NADH and H+, and a carbon dioxide molecule, forming a five carbon alpha-ketoglutarate.
This product releases another carbon dioxide molecule and two electrons, reducing another NAD+ to NADH and a proton. Leaving the molecule with an unstable bond, where a coenzyme A attaches forming succinyl CoA. In the next step, the coenzyme is replaced by a phosphate group. Then the phosphate is transferred to GDP forming succinate and GTP, which can be used to generate ATP.
During step six, succinate is oxidized with two electrons from hydrogen atoms, transformed to the electron carrier flavin adenine dinucleotide, FAD to produce FADH2 and fumarate. Water is then added to the resulting molecule and after bond rearrangement forms into malate.
Finally this molecule is oxidized, reducing NAD+ to NADH and H+, regenerating the original compound, oxaloacetate. In the end, each cycle produces three NADH and one FADH2. High energy electron carriers that are used in the electron transport chain.
View the full transcript and gain access to JoVE Core videos
Q1: What is the citric acid cycle and where does it occur?
The citric acid cycle is a closed loop of eight enzymatic reactions occurring in the mitochondrial matrix that is critical for glucose catabolism. Also called the Krebs cycle or TCA cycle, it processes acetyl CoA through a series of redox, dehydration, hydration, and decarboxylation reactions. The cycle regenerates oxaloacetate, allowing continuous energy extraction from glucose.
Q2: How does acetyl CoA enter the citric acid cycle?
Acetyl CoA, a two-carbon molecule produced from pyruvate oxidation production of acetyl coa in mitochondria, donates its acetyl group to oxaloacetate, a four-carbon molecule. This combination forms citrate, a six-carbon intermediate that initiates the cycle. The CoA group is released and diffuses away to combine with another acetyl group.
Q3: What are the main products generated by one turn of the citric acid cycle?
Each cycle produces three NADH molecules, one FADH2 molecule, one ATP (or GTP), and releases two carbon dioxide molecules. These electron carriers, NADH and FADH2, are high-energy molecules used in the electron transport chain to generate additional ATP through oxidative phosphorylation.
Q4: Why does the citric acid cycle run twice per glucose molecule?
Pyruvate oxidation produces two acetyl CoA molecules from each glucose molecule. Since the citric acid cycle processes one acetyl CoA per turn, the cycle must run twice to completely oxidize all carbons from a single glucose molecule and extract all available energy.
Q5: What happens during the oxidation steps of the citric acid cycle?
Oxidation steps reduce NAD+ to NADH and FAD to FADH2, capturing high-energy electrons. These reductions occur when isocitrate is oxidized to alpha-ketoglutarate, when alpha-ketoglutarate forms succinyl CoA, when succinate is oxidized to fumarate, and when malate is oxidized back to oxaloacetate.
Q6: How is ATP generated directly in the citric acid cycle?
During step five, a phosphate group replaces the CoA group on succinyl CoA, forming succinate. This phosphate is then transferred to GDP or ADP, producing GTP or ATP through substrate-level phosphorylation. This direct mechanism generates one ATP per cycle turn.
Q7: How do NADH and FADH2 contribute to overall ATP production?
NADH and FADH2 produced in the citric acid cycle provide electrons to the electron transport chain, which uses these electrons to pump protons across the inner mitochondrial membrane. This creates a proton gradient that drives ATP synthesis, generating the majority of ATP from glucose catabolism.