10.2 Citric acid cycle and oxidative phosphorylation
2 min read•july 22, 2024
The citric acid cycle and are key processes in cellular energy production. These pathways break down nutrients, generating electron carriers that power synthesis through a complex chain of reactions.
Understanding these processes is crucial for grasping how cells convert food into usable energy. From the initial breakdown of glucose to the final production of ATP, these pathways showcase the intricate mechanisms cells use to efficiently harvest energy from nutrients.
Citric Acid Cycle
Steps of citric acid cycle
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- combines with oxaloacetate forming catalyzed by citrate synthase
- Aconitase converts citrate to isocitrate through cis-aconitate intermediate
- Isocitrate dehydrogenase oxidatively decarboxylates isocitrate to α-ketoglutarate generating first (nicotinamide adenine dinucleotide) of cycle
- α-Ketoglutarate dehydrogenase complex oxidatively decarboxylates α-ketoglutarate to producing second NADH
- Succinyl-CoA synthetase converts succinyl-CoA to succinate generating GTP (guanosine triphosphate) or ATP (adenosine triphosphate)
- oxidizes succinate to fumarate reducing FAD (flavin adenine dinucleotide) to
- hydrates fumarate to malate
- oxidizes malate to oxaloacetate generating third NADH completing cycle
Reducing equivalents in citric acid cycle
- Citric acid cycle generates three NADH and one FADH2 per acetyl-CoA
- Isocitrate dehydrogenase, α-ketoglutarate dehydrogenase complex, and malate dehydrogenase produce NADH
- Succinate dehydrogenase produces FADH2
- NADH and FADH2 reducing equivalents donate electrons to driving oxidative phosphorylation
- Electron transport generates proton gradient used for ATP synthesis
Oxidative Phosphorylation
Structure of electron transport chain
- Electron transport chain has four protein complexes (I, II, III, IV) and two mobile electron carriers (, )
- (NADH dehydrogenase) transfers electrons from NADH to ubiquinone
- (succinate dehydrogenase) transfers electrons from FADH2 to ubiquinone
- (cytochrome bc1 complex) transfers electrons from ubiquinone to cytochrome c
- () transfers electrons from cytochrome c reducing oxygen to water
- Electron transport pumps protons from to intermembrane space
- Creates proton gradient with higher proton concentration in intermembrane space
Chemiosmosis and ATP synthesis
- uses proton gradient generated by electron transport chain to drive ATP synthesis
- ATP synthase enzyme complex utilizes proton gradient to generate ATP
- Protons flow down concentration gradient from intermembrane space to matrix through ATP synthase
- Proton flow rotates F0 subunit of ATP synthase driving conformational changes in F1 subunit
- Conformational changes catalyze ATP synthesis from ADP (adenosine diphosphate) and Pi (inorganic phosphate)
ATP yield from glucose oxidation
- Glycolysis: 2 ATP directly, 2 NADH (5 ATP via shuttle), total 7 ATP
- Pyruvate dehydrogenase complex: 2 NADH (5 ATP)
- Citric acid cycle per glucose: 2 ATP (or GTP), 6 NADH (15 ATP), 2 FADH2 (3 ATP), total 20 ATP
- Oxidative phosphorylation: 10 NADH (2 glycolysis, 2 pyruvate dehydrogenase, 6 citric acid cycle) and 2 FADH2 yield 28 ATP
- Complete glucose oxidation yields approximately 30-32 ATP total depending on shuttle efficiency and ATP synthase
Key Terms to Review (30)
Acetyl-CoA: Acetyl-CoA is a central metabolite in cellular metabolism, serving as a key substrate for energy production and biosynthesis. It is formed from the breakdown of carbohydrates, fats, and proteins, linking glycolysis and the citric acid cycle, and plays a critical role in converting energy from food into usable forms for the cell.
Allosteric regulation: Allosteric regulation is a mechanism by which the function of an enzyme is modulated by the binding of an effector molecule at a site other than the active site. This type of regulation allows enzymes to respond to changes in cellular conditions, fine-tuning metabolic pathways and ensuring efficient energy production and resource allocation.
Alpha-ketoglutarate: Alpha-ketoglutarate is a key intermediate in the citric acid cycle (Krebs cycle), formed from isocitrate through the action of the enzyme isocitrate dehydrogenase. It plays a crucial role in cellular respiration as it helps in energy production and serves as a precursor for amino acid synthesis. Additionally, alpha-ketoglutarate is involved in various metabolic pathways, linking carbohydrate, fat, and protein metabolism.
ATP: Adenosine triphosphate (ATP) is a nucleotide that serves as the primary energy currency of the cell, enabling various biochemical reactions. It is essential for energy transfer within cells, acting as a mediator for energy storage and utilization during metabolic processes. ATP plays a vital role in cellular respiration, photosynthesis, and other energy-related pathways, making it a central molecule in both plant and animal life.
ATP Synthase Function: ATP synthase is a crucial enzyme that synthesizes adenosine triphosphate (ATP) by utilizing a proton gradient across a membrane. This process occurs primarily during oxidative phosphorylation, where ATP synthase harnesses the energy from protons flowing back into the mitochondrial matrix to convert adenosine diphosphate (ADP) and inorganic phosphate into ATP, the main energy currency of the cell. Its operation is tightly linked to both the citric acid cycle and the electron transport chain, making it essential for cellular respiration and energy production.
Chemiosmosis: Chemiosmosis is the process by which ATP (adenosine triphosphate) is produced in cells by the movement of protons (H+) across a membrane, generating a proton gradient that drives ATP synthesis. This mechanism is crucial for energy production during cellular respiration and photosynthesis, linking the flow of electrons to the synthesis of ATP through ATP synthase.
Citrate: Citrate is a key intermediate in the citric acid cycle, also known as the Krebs cycle, which is essential for energy production in cellular respiration. Formed when acetyl-CoA combines with oxaloacetate, citrate plays a crucial role in metabolic pathways by linking carbohydrate, fat, and protein metabolism. Its conversion back to oxaloacetate helps in generating ATP through oxidative phosphorylation.
CO2: CO2, or carbon dioxide, is a colorless, odorless gas that is a crucial byproduct of cellular respiration and plays a significant role in the metabolic processes of living organisms. In the context of energy production, it is generated during the citric acid cycle and oxidative phosphorylation, where organic molecules are broken down to produce ATP while releasing CO2 as a waste product, which must be expelled from the cell to maintain cellular homeostasis.
Complex I: Complex I, also known as NADH:ubiquinone oxidoreductase, is the first enzyme complex in the electron transport chain, playing a crucial role in cellular respiration by transferring electrons from NADH to ubiquinone (coenzyme Q). This process is vital for generating a proton gradient across the inner mitochondrial membrane, which is essential for ATP production during oxidative phosphorylation.
Complex II: Complex II, also known as succinate dehydrogenase, is an essential enzyme complex in the mitochondrial electron transport chain that facilitates the transfer of electrons from succinate to ubiquinone (coenzyme Q). It plays a dual role in both the citric acid cycle, where it converts succinate to fumarate, and in oxidative phosphorylation, where it contributes to ATP production by facilitating electron transfer and proton pumping across the inner mitochondrial membrane.
Complex III: Complex III, also known as cytochrome bc1 complex, is a crucial component of the electron transport chain located in the inner mitochondrial membrane. It plays a key role in the process of oxidative phosphorylation by facilitating the transfer of electrons from coenzyme Q (ubiquinone) to cytochrome c while simultaneously pumping protons into the intermembrane space. This proton gradient generated by Complex III is essential for ATP synthesis, connecting its function to cellular respiration and energy production.
Complex IV: Complex IV, also known as cytochrome c oxidase, is the final enzyme in the electron transport chain of oxidative phosphorylation, where it catalyzes the transfer of electrons from cytochrome c to molecular oxygen, reducing it to water. This process is crucial for aerobic respiration as it plays a key role in establishing the proton gradient across the inner mitochondrial membrane, which ultimately drives ATP synthesis.
Cytochrome c: Cytochrome c is a small heme protein found in the mitochondria of eukaryotic cells, playing a crucial role in the electron transport chain and cellular respiration. It functions as an electron carrier, shuttling electrons between complex III and complex IV, and is essential for ATP production during oxidative phosphorylation. Additionally, cytochrome c has important implications in programmed cell death, linking energy metabolism to apoptosis.
Cytochrome c oxidase: Cytochrome c oxidase is an essential enzyme in the electron transport chain, primarily responsible for the final step of cellular respiration where it catalyzes the transfer of electrons from cytochrome c to molecular oxygen. This process is crucial for ATP production as it helps maintain the proton gradient across the inner mitochondrial membrane, which drives ATP synthase. Its role connects the citric acid cycle and oxidative phosphorylation by coupling the oxidation of substrates to the reduction of oxygen, facilitating aerobic metabolism.
Electron transport chain: The electron transport chain (ETC) is a series of protein complexes and other molecules located in the inner mitochondrial membrane that transfer electrons from electron donors to electron acceptors via redox reactions. This process plays a crucial role in cellular respiration and photosynthesis, as it helps produce ATP, the energy currency of the cell, by creating a proton gradient that drives ATP synthesis.
FADH2: FADH2 is a reduced form of flavin adenine dinucleotide, an important electron carrier in cellular respiration. It plays a crucial role in energy production by transporting electrons to the electron transport chain, contributing to the generation of ATP during oxidative phosphorylation.
Feedback Inhibition: Feedback inhibition is a regulatory mechanism in cellular processes where the end product of a metabolic pathway inhibits an enzyme involved in its own synthesis. This process helps maintain homeostasis by preventing the overproduction of substances, allowing cells to efficiently manage their resources and respond to changes in their environment.
Fumarase: Fumarase, also known as fumarate hydratase, is an enzyme that catalyzes the reversible conversion of fumarate to malate in the citric acid cycle. This reaction is crucial for cellular respiration, linking carbohydrate metabolism to the generation of ATP and reducing equivalents that are essential for oxidative phosphorylation. Fumarase plays a key role in maintaining the flow of metabolites through the citric acid cycle, ensuring energy production in aerobic organisms.
Inner mitochondrial membrane: The inner mitochondrial membrane is a highly folded membrane that encloses the mitochondrial matrix and is essential for the process of oxidative phosphorylation. It contains numerous proteins and complexes involved in the electron transport chain and ATP synthesis, making it critical for energy production in eukaryotic cells. The unique structure of this membrane, with its extensive surface area due to cristae, enables efficient ATP generation through chemiosmosis.
Krebs Cycle: The Krebs Cycle, also known as the Citric Acid Cycle, is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. This cycle takes place in the mitochondria and is a crucial component of cellular respiration, connecting to oxidative phosphorylation where the energy produced is ultimately used to create ATP.
Malate dehydrogenase: Malate dehydrogenase is an enzyme that catalyzes the conversion of malate to oxaloacetate, a key step in the citric acid cycle. This reaction is crucial because it helps regenerate oxaloacetate, allowing the cycle to continue and ultimately contributing to the production of energy in the form of ATP. It also plays a role in the interconnected metabolic pathways of cellular respiration and energy production.
Mitochondrial matrix: The mitochondrial matrix is the innermost compartment of a mitochondrion, surrounded by the inner mitochondrial membrane. It plays a critical role in cellular respiration and energy production, housing key enzymes, mitochondrial DNA, and ribosomes necessary for various metabolic processes. This environment is essential for the citric acid cycle and oxidative phosphorylation, where energy-rich molecules are produced from the breakdown of carbohydrates and fats.
NADH: NADH, or nicotinamide adenine dinucleotide (in its reduced form), is a crucial coenzyme that plays a significant role in cellular respiration and metabolism. It serves as an electron carrier, transporting electrons from one reaction to another, particularly in processes like glycolysis, the citric acid cycle, and oxidative phosphorylation. By accepting and donating electrons, NADH is key in generating ATP, the energy currency of the cell.
Oxidative phosphorylation: Oxidative phosphorylation is the metabolic process in which cells use energy derived from the electron transport chain to produce adenosine triphosphate (ATP) through the transfer of electrons. This process occurs in the inner mitochondrial membrane and is crucial for aerobic respiration, as it efficiently generates ATP by coupling electron transport to ATP synthesis, ultimately using oxygen as the final electron acceptor.
Oxidative phosphorylation mechanism: The oxidative phosphorylation mechanism is a critical biochemical process that generates ATP, the energy currency of the cell, through the transfer of electrons along the electron transport chain and the coupling of proton gradients across the inner mitochondrial membrane. This process occurs in two main stages: the electron transport chain, where electrons derived from NADH and FADH₂ are transferred to oxygen, and chemiosmosis, where ATP synthase utilizes the resulting proton gradient to synthesize ATP. This mechanism is intricately linked with the citric acid cycle, which provides the reduced cofactors that fuel electron transport.
Substrate-level phosphorylation: Substrate-level phosphorylation is a metabolic process in which a phosphate group is directly transferred from a substrate molecule to ADP, forming ATP without the involvement of an electron transport chain. This process occurs in several key pathways of cellular respiration, where energy-rich molecules are broken down, leading to the generation of ATP through direct enzymatic action.
Succinate dehydrogenase: Succinate dehydrogenase is an enzyme that plays a critical role in the citric acid cycle by catalyzing the oxidation of succinate to fumarate while reducing ubiquinone to ubiquinol. This enzyme is unique as it is the only one that participates in both the citric acid cycle and the electron transport chain, linking these two essential metabolic pathways. Its function is crucial for energy production in aerobic respiration.
Succinyl-CoA: Succinyl-CoA is a key intermediate in the citric acid cycle (Krebs cycle) that plays an essential role in cellular respiration. It is formed from the condensation of acetate with oxaloacetate and is crucial for the production of ATP through substrate-level phosphorylation, as well as for the synthesis of heme groups in hemoglobin and myoglobin. This compound highlights the interconnectedness of metabolic pathways, demonstrating how energy production is linked with biosynthetic processes.
Tricarboxylic acid cycle: The tricarboxylic acid cycle, also known as the citric acid cycle or Krebs cycle, is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. This cycle plays a crucial role in cellular respiration, connecting metabolic pathways and providing electrons for oxidative phosphorylation, where ATP is produced.
Ubiquinone: Ubiquinone, also known as coenzyme Q10, is a vital electron carrier in the electron transport chain, playing a crucial role in cellular respiration. It facilitates the transfer of electrons from complexes I and II to complex III, which is essential for ATP production. Ubiquinone also acts as an antioxidant, helping to protect cells from oxidative damage, making it significant in both energy metabolism and cellular health.