13.1 Overview and Steps of the Citric Acid Cycle
3 min read•august 9, 2024
The citric acid cycle is a crucial metabolic pathway that breaks down , producing energy and important molecules. It involves a series of reactions that release , generate , and create reduced electron carriers like and .
This cycle is a key part of cellular respiration, connecting glycolysis to the . It occurs in the of eukaryotes and the cytoplasm of prokaryotes, playing a vital role in for cells.
Citric Acid Cycle Overview
Acetyl-CoA and Initial Reactions
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- Acetyl-CoA enters the citric acid cycle as a two-carbon molecule
- Acetyl-CoA combines with (four-carbon molecule) to form (six-carbon molecule)
- catalyzes the condensation reaction between acetyl-CoA and oxaloacetate
- This reaction marks the first step of the citric acid cycle
- Citrate synthase releases coenzyme A and produces citrate
Carbon Dioxide Release and Energy Production
- The citric acid cycle releases two molecules of CO2 per acetyl-CoA
- CO2 release occurs during steps
- The cycle produces energy in the form of (guanosine triphosphate)
- GTP can be converted to ATP through
- The cycle also generates reduced electron carriers (NADH and FADH2)
Cycle Completion and Regeneration
- Oxaloacetate regenerates at the end of each cycle
- Regenerated oxaloacetate can combine with another acetyl-CoA molecule
- This regeneration allows the cycle to continue indefinitely
- The cycle occurs in the mitochondrial matrix of eukaryotic cells
- Prokaryotes perform the citric acid cycle in their cytoplasm
Oxidative Decarboxylation Steps
Isocitrate Dehydrogenase Reaction
- catalyzes the oxidative decarboxylation of isocitrate
- This reaction converts isocitrate to α-ketoglutarate
- The process releases one molecule of CO2
- Simultaneously produces one molecule of NADH
- Isocitrate dehydrogenase requires NAD+ as a cofactor
α-Ketoglutarate Dehydrogenase Complex
- α-Ketoglutarate dehydrogenase complex catalyzes the next oxidative decarboxylation
- Converts α-ketoglutarate to
- Releases the second molecule of CO2 in the cycle
- Generates another molecule of NADH
- Requires thiamine pyrophosphate, lipoic acid, and NAD+ as cofactors
NADH Production and Electron Transport Chain
- The citric acid cycle produces a total of three NADH molecules per acetyl-CoA
- NADH serves as a high-energy electron carrier
- Transfers electrons to the electron transport chain
- Electron transport chain uses these electrons for ATP production via
- Each NADH can lead to the production of approximately 2.5 ATP molecules
Regeneration of Oxaloacetate
Succinyl-CoA to Succinate Conversion
- Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to
- This reaction produces GTP through substrate-level phosphorylation
- GTP can be converted to ATP by nucleoside diphosphate kinase
- Succinyl-CoA synthetase requires ADP or GDP as a phosphate acceptor
- This step marks the only substrate-level phosphorylation in the citric acid cycle
Succinate Oxidation and FADH2 Production
- oxidizes succinate to
- This reaction reduces FAD to FADH2
- Succinate dehydrogenase anchored in the inner mitochondrial membrane
- FADH2 transfers electrons directly to the electron transport chain
- Each FADH2 leads to the production of approximately 1.5 ATP molecules
Final Steps and Oxaloacetate Formation
- Fumarase catalyzes the hydration of fumarate to
- oxidizes malate to oxaloacetate
- This final step produces another molecule of NADH
- Regenerated oxaloacetate can combine with a new acetyl-CoA to restart the cycle
- Malate dehydrogenase requires NAD+ as a cofactor
Key Terms to Review (26)
Acetyl-CoA: Acetyl-CoA is a central metabolite in cellular metabolism that consists of an acetyl group (derived from carbohydrates, fats, and proteins) linked to coenzyme A. It serves as a key substrate for the citric acid cycle, enabling the conversion of fuel molecules into energy through oxidative phosphorylation. Additionally, acetyl-CoA plays a critical role in regulating metabolic pathways and acts as a key signaling molecule in energy production.
Alpha-ketoglutarate: Alpha-ketoglutarate is a key intermediate in the citric acid cycle, playing a critical role in cellular respiration and energy production. It is formed from isocitrate through a dehydrogenation reaction, producing NADH and CO2, and can also act as a substrate for various metabolic pathways, including amino acid synthesis and degradation.
Alpha-ketoglutarate dehydrogenase complex: The alpha-ketoglutarate dehydrogenase complex is a multi-enzyme complex that catalyzes the conversion of alpha-ketoglutarate to succinyl-CoA in the citric acid cycle. This reaction is vital as it plays a key role in the energy production pathway, linking carbohydrate metabolism to energy generation while also producing NADH, which is essential for ATP synthesis.
ATP: ATP, or adenosine triphosphate, is the primary energy currency of the cell, providing the energy needed for various biochemical reactions. It plays a critical role in metabolic processes, serving as a link between energy-releasing pathways and energy-consuming activities within the cell.
Biosynthesis of precursors: Biosynthesis of precursors refers to the biochemical processes through which essential building blocks or intermediate compounds are produced, serving as the starting materials for the synthesis of larger biomolecules. This process is crucial for cell metabolism and functions, as it enables the conversion of simpler substrates into complex molecules such as amino acids, nucleotides, and fatty acids, which are essential for cellular structures and functions.
Carbon dioxide: Carbon dioxide (CO₂) is a colorless gas produced during the metabolic processes of living organisms, primarily through cellular respiration. It plays a crucial role in the citric acid cycle, where it is generated as a byproduct and is essential for maintaining the balance of carbon in biological systems.
Citrate: Citrate is a key intermediate in metabolic pathways, particularly in the citric acid cycle, where it is formed by the condensation of acetyl-CoA and oxaloacetate. It plays a significant role in energy production and is involved in regulating various metabolic processes, including gluconeogenesis and fatty acid synthesis.
Citrate synthase: Citrate synthase is a key enzyme in the citric acid cycle that catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate. This reaction represents the first step in the cycle and is crucial for energy production, as it marks the beginning of the process that generates ATP through the oxidation of acetyl-CoA.
Electron transport chain: The electron transport chain is a series of protein complexes located in the inner mitochondrial membrane that facilitate the transfer of electrons from electron donors, such as NADH and FADH2, to electron acceptors, ultimately generating ATP through oxidative phosphorylation. This process plays a critical role in cellular respiration and is essential for converting energy stored in nutrients into a usable form for the cell.
Energy production: Energy production refers to the biochemical processes that generate ATP, the primary energy currency of cells, through various metabolic pathways. These processes are vital for maintaining cellular functions and involve complex reactions such as oxidation-reduction reactions, substrate-level phosphorylation, and chemiosmosis. The efficiency and regulation of these pathways can vary significantly depending on the physiological state of the organism.
Fadh2: FADH2 is a redox-active coenzyme that plays a vital role in cellular respiration, particularly in the citric acid cycle and oxidative phosphorylation. It serves as an electron carrier, transporting electrons to the electron transport chain, where its reduction potential helps drive ATP synthesis through the chemiosmotic mechanism. By accepting electrons from metabolic substrates, FADH2 contributes significantly to the production of energy within the cell.
Feedback inhibition: Feedback inhibition is a regulatory mechanism in which the end product of a metabolic pathway inhibits an earlier step in that pathway, preventing the overproduction of the product. This process helps maintain homeostasis within the cell and ensures that resources are not wasted when sufficient product levels are reached.
Fumarate: Fumarate is a key intermediate in the citric acid cycle, formed from the oxidation of succinate and further converted into malate. It plays a crucial role in cellular respiration, linking the metabolism of carbohydrates, fats, and proteins to energy production. Fumarate's conversion is catalyzed by the enzyme fumarase, highlighting its significance in metabolic pathways and energy yield.
GTP: GTP, or guanosine triphosphate, is a nucleotide similar to ATP that serves as a crucial energy source and signaling molecule within cells. It plays a significant role in various biochemical processes, including protein synthesis, signal transduction, and the functioning of the citric acid cycle. GTP is also involved in the regulation of certain enzymatic reactions and is essential for the conversion of substrates during the cycle.
Isocitrate dehydrogenase: Isocitrate dehydrogenase is an enzyme that plays a critical role in the citric acid cycle (Krebs cycle) by catalyzing the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, producing NADH and releasing carbon dioxide. This reaction is essential for energy production and links carbohydrate metabolism to the Krebs cycle, showcasing its importance in cellular respiration and metabolism regulation.
Malate: Malate is a four-carbon dicarboxylic acid that plays a crucial role in the citric acid cycle, also known as the Krebs cycle. It is formed from fumarate through the action of the enzyme fumarase and is subsequently converted to oxaloacetate by malate dehydrogenase, facilitating energy production in cellular respiration. Malate serves as an important intermediate, helping to shuttle electrons and protons during metabolic processes.
Malate dehydrogenase: Malate dehydrogenase is an enzyme that catalyzes the reversible conversion of malate to oxaloacetate, while reducing NAD+ to NADH in the process. This enzyme plays a crucial role in the citric acid cycle, facilitating energy production by linking the cycle's reactions and contributing to cellular respiration. By participating in the interconversion of key metabolic intermediates, malate dehydrogenase is essential for maintaining the flow of carbon and energy through the cycle.
Mitochondrial matrix: The mitochondrial matrix is the innermost compartment of mitochondria, where crucial metabolic reactions occur. It contains enzymes for the citric acid cycle, DNA, ribosomes, and a variety of metabolites essential for energy production and biosynthesis. This space plays a vital role in cellular respiration and energy production, linking directly to processes that regulate energy metabolism and overall cellular function.
NADH: NADH, or Nicotinamide Adenine Dinucleotide (Reduced form), is a crucial coenzyme found in all living cells that plays a key role in cellular respiration and energy production. It acts as an electron carrier, facilitating the transfer of electrons in metabolic processes, particularly during glycolysis and the citric acid cycle, ultimately contributing to ATP synthesis via oxidative phosphorylation.
Oxaloacetate: Oxaloacetate is a four-carbon dicarboxylic acid that plays a critical role in metabolism, primarily as an intermediate in the citric acid cycle. It serves as a key starting point for gluconeogenesis, contributing to glucose synthesis when carbohydrates are scarce, and it is essential for replenishing citric acid cycle intermediates through anaplerotic reactions. Oxaloacetate's regulation and availability influence various metabolic pathways and energy production.
Oxidative decarboxylation: Oxidative decarboxylation is a biochemical reaction where a carboxyl group is removed from a molecule, releasing carbon dioxide (CO₂) and transferring electrons to electron carriers. This process is crucial in energy production as it links glycolysis and the citric acid cycle, facilitating the conversion of pyruvate into acetyl-CoA, a key substrate for energy generation.
Oxidative phosphorylation: Oxidative phosphorylation is the process by which ATP is produced in cells through the electron transport chain and the chemiosmotic coupling of protons across a membrane. This process is crucial for cellular energy production, linking the breakdown of nutrients to ATP synthesis, and is tightly regulated to meet cellular energy demands.
Substrate-level phosphorylation: Substrate-level phosphorylation is a metabolic process in which a phosphate group is directly transferred to ADP from a phosphorylated intermediate, resulting in the formation of ATP. This process occurs independently of the electron transport chain and is essential for energy production during glycolysis and the citric acid cycle.
Succinate: Succinate is a four-carbon dicarboxylic acid that plays a crucial role in the citric acid cycle as an intermediate metabolite. It is formed during the conversion of succinyl-CoA to succinate, coupled with the production of GTP or ATP. This compound is not only vital for energy production but also serves as a precursor for the synthesis of various biomolecules, linking metabolic pathways such as the Krebs cycle and the electron transport chain.
Succinate dehydrogenase: Succinate dehydrogenase is an enzyme that plays a crucial role in both the citric acid cycle and the electron transport chain, catalyzing the oxidation of succinate to fumarate while reducing ubiquinone to ubiquinol. This dual function makes it unique as it bridges metabolic pathways by being part of both the Krebs cycle and oxidative phosphorylation.
Succinyl-CoA: Succinyl-CoA is a key intermediate in the citric acid cycle, formed from the oxidation of isocitrate and playing an important role in energy production. It serves as a substrate for succinate synthesis and is also crucial for the biosynthesis of heme, which is essential for oxygen transport in the blood. Its involvement in these metabolic pathways connects it to both energy metabolism and amino acid synthesis.