Krebs cycle
59 flashcards covering Krebs cycle for the MCAT Biology & Biochemistry section.
The Krebs cycle, also known as the citric acid cycle, is a key metabolic process in cells that generates energy from nutrients. It occurs in the mitochondria and involves a series of enzyme-driven reactions that start with acetyl-CoA, breaking it down to produce high-energy molecules like ATP, NADH, and FADH2. This cycle plays a crucial role in cellular respiration, linking the breakdown of carbohydrates, fats, and proteins to the production of usable energy, making it essential for understanding how cells sustain life.
On the MCAT, the Krebs cycle often appears in biology and biochemistry questions, typically as multiple-choice items testing your knowledge of its steps, intermediates, and connections to other pathways like glycolysis or the electron transport chain. Common traps include confusing the cycle's inputs and outputs, such as mistaking oxaloacetate for a product, or overlooking its regulation by energy levels. Focus on mastering the eight main steps, key enzymes like isocitrate dehydrogenase, and the net yield of molecules to handle these questions effectively.
A helpful tip: Draw the cycle from memory to reinforce the sequence.
Terms (59)
- 01
Krebs cycle
A metabolic pathway in the mitochondria that oxidizes acetyl-CoA to produce energy carriers like NADH and FADH2, generating ATP through substrate-level phosphorylation and linking to the electron transport chain.
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Citric acid cycle
The same process as the Krebs cycle, named for the initial formation of citrate from acetyl-CoA and oxaloacetate, and it completes the breakdown of nutrients for energy production.
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Acetyl-CoA entry
The two-carbon acetyl group from acetyl-CoA combines with four-carbon oxaloacetate to form six-carbon citrate, marking the start of the Krebs cycle.
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Citrate
The first intermediate in the Krebs cycle, formed by the condensation of acetyl-CoA and oxaloacetate, and it undergoes isomerization to continue the cycle.
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Citrate synthase
The enzyme that catalyzes the first step of the Krebs cycle, joining acetyl-CoA and oxaloacetate to produce citrate while releasing coenzyme A.
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Aconitase
The enzyme that converts citrate to isocitrate by removing and adding water, facilitating the isomerization in the Krebs cycle.
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Isocitrate
A six-carbon intermediate in the Krebs cycle that is dehydrogenated and decarboxylated to produce NADH and CO2.
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Isocitrate dehydrogenase
The enzyme that oxidizes isocitrate to alpha-ketoglutarate, producing NADH and releasing CO2, and it is a key regulatory point in the cycle.
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Alpha-ketoglutarate
A five-carbon intermediate in the Krebs cycle that is further oxidized and decarboxylated to form succinyl-CoA, yielding NADH and CO2.
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Alpha-ketoglutarate dehydrogenase complex
The multi-enzyme complex that converts alpha-ketoglutarate to succinyl-CoA, producing NADH and CO2, similar to the pyruvate dehydrogenase complex.
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Succinyl-CoA
A four-carbon intermediate in the Krebs cycle that is converted to succinate, with the reaction coupled to substrate-level phosphorylation to produce GTP or ATP.
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Succinyl-CoA synthetase
The enzyme that hydrolyzes succinyl-CoA to succinate, generating GTP (or ATP in some tissues) through substrate-level phosphorylation.
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Succinate
A four-carbon intermediate in the Krebs cycle that is oxidized to fumarate, producing FADH2 via succinate dehydrogenase.
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Succinate dehydrogenase
The enzyme that oxidizes succinate to fumarate in the Krebs cycle, also part of the electron transport chain as Complex II.
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Fumarate
A four-carbon intermediate in the Krebs cycle that is hydrated to form malate, an essential step in the pathway's progression.
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Fumarase
The enzyme that adds water to fumarate to produce malate, a hydration reaction in the Krebs cycle.
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Malate
A four-carbon intermediate in the Krebs cycle that is oxidized to oxaloacetate, regenerating the cycle and producing NADH.
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Malate dehydrogenase
The enzyme that oxidizes malate to oxaloacetate in the final step of the Krebs cycle, producing NADH.
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Oxaloacetate
The four-carbon compound that accepts acetyl-CoA to start the Krebs cycle and is regenerated at the end, allowing the cycle to continue.
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NADH production in Krebs cycle
The Krebs cycle produces three molecules of NADH per turn from the dehydrogenation steps, which are used to generate ATP in the electron transport chain.
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FADH2 production in Krebs cycle
One molecule of FADH2 is produced per turn of the Krebs cycle during the oxidation of succinate, contributing to ATP synthesis via the electron transport chain.
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GTP production in Krebs cycle
Substrate-level phosphorylation by succinyl-CoA synthetase yields one GTP per turn, which can be converted to ATP for cellular energy needs.
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Overall equation of Krebs cycle
The net reaction per acetyl-CoA is: acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O → 2 CO2 + 3 NADH + FADH2 + GTP + 2 H+ + CoA.
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Energy yield per acetyl-CoA
One turn of the Krebs cycle from one acetyl-CoA yields 3 NADH, 1 FADH2, and 1 GTP, which typically equate to about 12 ATP molecules through oxidative phosphorylation.
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Amphibolic nature of Krebs cycle
The Krebs cycle serves both catabolic and anabolic roles, breaking down acetyl-CoA for energy while providing intermediates for biosynthesis, such as amino acids.
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Regulation by ATP
High ATP levels inhibit enzymes like citrate synthase and isocitrate dehydrogenase, slowing the Krebs cycle when energy is abundant.
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Regulation by NADH
Accumulation of NADH inhibits isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase, preventing overproduction of reducing equivalents.
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Anaplerotic reactions
Reactions that replenish Krebs cycle intermediates, such as the conversion of pyruvate to oxaloacetate, to maintain cycle flux during biosynthesis.
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Link to glycolysis
The Krebs cycle receives pyruvate from glycolysis via conversion to acetyl-CoA, integrating carbohydrate metabolism with mitochondrial energy production.
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Link to electron transport chain
NADH and FADH2 from the Krebs cycle donate electrons to the electron transport chain, driving ATP synthesis through oxidative phosphorylation.
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Carbon atoms in Krebs cycle
Acetyl-CoA contributes two carbons that are eventually released as CO2 in the steps involving isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase.
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Inhibitors of citrate synthase
High levels of NADH and succinyl-CoA can inhibit citrate synthase, regulating the entry of acetyl-CoA into the Krebs cycle.
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Dehydrogenation reactions
Several steps in the Krebs cycle involve the removal of hydrogen atoms, producing NADH or FADH2, which are crucial for energy transfer.
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Decarboxylation reactions
Two decarboxylation steps in the Krebs cycle release CO2 from isocitrate and alpha-ketoglutarate, reducing the carbon chain length.
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Substrate-level phosphorylation
The only ATP or GTP production method in the Krebs cycle occurs at succinyl-CoA synthetase, directly transferring a phosphate group.
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Mitochondrial location
The Krebs cycle occurs in the mitochondrial matrix, allowing proximity to the electron transport chain for efficient energy harnessing.
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Role in fatty acid oxidation
Acetyl-CoA from beta-oxidation of fatty acids enters the Krebs cycle, linking lipid metabolism to ATP production.
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Common trap: Confusing with glycolysis
Unlike glycolysis, which occurs in the cytoplasm and produces net ATP without oxygen dependence, the Krebs cycle requires oxygen and produces electron carriers.
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Strategy for memorizing steps
Break the Krebs cycle into phases: condensation, isomerization, oxidative decarboxylation, and regeneration, to recall the sequence of intermediates and reactions.
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Net products per glucose
Two turns of the Krebs cycle per glucose molecule yield 6 NADH, 2 FADH2, and 2 GTP, contributing to the majority of ATP in cellular respiration.
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pH sensitivity in Krebs cycle
Many enzymes in the cycle, like isocitrate dehydrogenase, are sensitive to pH changes, which can affect their activity and overall metabolic rate.
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Role of coenzymes
NAD+ and FAD act as coenzymes in the Krebs cycle, accepting electrons to become NADH and FADH2 for subsequent energy production.
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Irreversible steps
The reactions catalyzed by citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase are typically irreversible, serving as control points.
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Bypass reactions
In some conditions, like in plants, alternative pathways such as the glyoxylate cycle bypass certain Krebs steps to conserve carbon for biosynthesis.
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Quantifying ATP from NADH
Each NADH from the Krebs cycle typically yields 2.5 ATP in the electron transport chain, though this can vary based on shuttle systems.
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Quantifying ATP from FADH2
Each FADH2 from the Krebs cycle yields about 1.5 ATP, as it enters the electron transport chain at a lower energy level than NADH.
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Feedback inhibition
Products like ATP and NADH provide feedback inhibition to early enzymes in the Krebs cycle to match energy production with cellular demand.
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Interconnection with amino acids
Several Krebs intermediates, such as alpha-ketoglutarate and oxaloacetate, can be transaminated to form amino acids like glutamate and aspartate.
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Example of one turn
In one turn, acetyl-CoA enters and is fully oxidized, producing 2 CO2, 3 NADH, 1 FADH2, and 1 GTP, as seen in a typical metabolic pathway diagram.
For a molecule derived from glucose, this turn accounts for the oxidation of two carbons.
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High-energy intermediates
Compounds like succinyl-CoA store energy in their thioester bonds, which is harnessed to produce GTP during the cycle.
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Oxidative steps
The majority of the Krebs cycle involves oxidation reactions that generate reducing power for ATP synthesis.
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Hydration and dehydration
Steps like the conversion of fumarate to malate involve hydration, while earlier steps may include dehydration, balancing water usage in the cycle.
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Allosteric regulation
Enzymes in the Krebs cycle, such as isocitrate dehydrogenase, are allosterically regulated by molecules like ATP to fine-tune metabolic flux.
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Mitochondrial diseases impact
Defects in Krebs cycle enzymes can lead to energy deficits, as seen in diseases like fumarase deficiency, affecting cellular function.
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Comparison to beta-oxidation
While beta-oxidation produces acetyl-CoA from fats, the Krebs cycle oxidizes it further, highlighting their sequential roles in energy metabolism.
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pKa relevance
The pKa of intermediates like alpha-ketoglutarate influences their ionization state, affecting enzyme binding in the Krebs cycle.
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Thermodynamic favorability
The Krebs cycle reactions are exergonic overall, driven by the removal of CO2 and the reduction of NAD+ and FAD.
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Stoichiometry per cycle
Each turn processes one acetyl-CoA, consuming oxygen indirectly and producing reducing equivalents for the cell.
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Evolutionary significance
The Krebs cycle is an ancient pathway that evolved to efficiently extract energy from organic molecules in aerobic organisms.