Krebs Cycle Overview
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Questions and Answers

What is the primary role of the citric acid cycle in cellular metabolism?

  • Facilitating energy production and biosynthesis (correct)
  • Breaking down fatty acids for energy
  • Producing glucose from fatty acids
  • Regulating blood sugar levels

Which molecule is formed by the reaction of oxaloacetate and Acetyl-CoA?

  • Isocitrate
  • Succinate
  • Cis-aconitate
  • Citrate (correct)

Where do the enzymatic reactions of the citric acid cycle take place?

  • On the surface of the cell membrane
  • In the cytoplasm of the cell
  • In the nucleus of the cell
  • In the matrix of the mitochondria (correct)

What is released during the formation of citrate from Acetyl-CoA and oxaloacetate?

<p>CoASH (D)</p> Signup and view all the answers

Which enzyme mediates the isomerization of citrate to isocitrate?

<p>Aconitase (B)</p> Signup and view all the answers

What intermediate is formed during the isomerization of citrate to isocitrate?

<p>Cis-aconitate (D)</p> Signup and view all the answers

Which of the following statements is true regarding the citric acid cycle?

<p>Enzymatic reactions are found in all cells using oxygen (C)</p> Signup and view all the answers

Which stage of cellular metabolism immediately follows the citric acid cycle?

<p>Electron transport chain (A)</p> Signup and view all the answers

What is the starting molecule for the Kreb Cycle?

<p>Oxaloacetate (B)</p> Signup and view all the answers

How many reactions are there in the Kreb Cycle?

<p>8 (B)</p> Signup and view all the answers

What happens to the acetyl group during the Kreb Cycle?

<p>It is completely broken apart. (B)</p> Signup and view all the answers

What is the primary function of the Succinyl-CoA synthetase?

<p>To phosphorylate GDP to form GTP (A)</p> Signup and view all the answers

Which atom in oxaloacetate is released as carbon dioxide during the cycle?

<p>Two carbon atoms from the original oxaloacetate (B)</p> Signup and view all the answers

What process regenerates the same metabolite at the end of the Kreb Cycle?

<p>The metabolic cycle (D)</p> Signup and view all the answers

Which cofactor is released during the action of Succinyl-CoA synthetase?

<p>Coenzyme A (A)</p> Signup and view all the answers

What role does the lipoamide cofactor play in the E2 complex?

<p>It releases electrons to restore FADH2. (B)</p> Signup and view all the answers

Which enzyme is primarily involved in the first step of the Kreb Cycle?

<p>Citrate Synthase (D)</p> Signup and view all the answers

In addition to a small molecule starting point, what type of group does the Kreb Cycle incorporate?

<p>Acetyl group (B)</p> Signup and view all the answers

What product is formed when succinate is oxidized by succinate dehydrogenase?

<p>Fumarate (B)</p> Signup and view all the answers

Where is succinate dehydrogenase located?

<p>In the mitochondrial membrane (B)</p> Signup and view all the answers

What is the end product of the Kreb Cycle that can be reused to begin another cycle?

<p>Oxaloacetate (D)</p> Signup and view all the answers

What happens to the hydrogen atoms extracted from succinate during its oxidation?

<p>They are transferred to FAD. (A)</p> Signup and view all the answers

In addition to its role in the citric acid cycle, what is another function of succinate dehydrogenase?

<p>It directly transfers electrons to the electron transport chain. (B)</p> Signup and view all the answers

What is the equivalent energy currency produced by Succinyl-CoA synthetase?

<p>GTP (D)</p> Signup and view all the answers

What is the primary function of the alpha-ketoglutarate dehydrogenase (KGDH) enzyme?

<p>To form CO2 and NADH while producing Succinyl-CoA (D)</p> Signup and view all the answers

Which cofactor is NOT used by the alpha-ketoglutarate dehydrogenase?

<p>Coenzyme A (A)</p> Signup and view all the answers

In the mechanism of KGDH, which component attacks the carbonyl carbon of alpha-ketoglutarate?

<p>TPP (A)</p> Signup and view all the answers

What structural change occurs at the C2 position during the reaction catalyzed by KGDH?

<p>Formation of a ketone functional group (D)</p> Signup and view all the answers

What molecules are produced during the reaction catalyzed by isocitrate dehydrogenase?

<p>α-Ketoglutarate and CO2 (C)</p> Signup and view all the answers

How does KGDH's mechanism compare to that of the pyruvate dehydrogenase (PDH) complex?

<p>Both have similar mechanisms and liberate CO2 (D)</p> Signup and view all the answers

Which cofactor is NOT utilized by isocitrate dehydrogenase during its reaction?

<p>FAD (D)</p> Signup and view all the answers

What role does lipoamide play in the KGDH reaction?

<p>It transfers the remaining succinyl group after CO2 release (C)</p> Signup and view all the answers

What role does NAD+ play in the reaction mechanism of isocitrate dehydrogenase?

<p>It acts as a cofactor that accepts electrons. (A)</p> Signup and view all the answers

What is produced alongside Succinyl-CoA during the KGDH catalytic process?

<p>NADH (A)</p> Signup and view all the answers

What is the primary function of the acidic residue in the active site of isocitrate dehydrogenase?

<p>To deprotonate the alcohol of isocitrate (C)</p> Signup and view all the answers

In the second step of the reaction, which type of activity does isocitrate dehydrogenase primarily perform?

<p>Decarboxylation (D)</p> Signup and view all the answers

Which substrate is directly involved in the mechanism of KGDH?

<p>Alpha-ketoglutarate (D)</p> Signup and view all the answers

What product is formed as an intermediate during the decarboxylation step of the reaction?

<p>Alkene (D)</p> Signup and view all the answers

How does Mg2+ contribute to the function of isocitrate dehydrogenase?

<p>It stabilizes charged intermediates. (D)</p> Signup and view all the answers

Why is isocitrate dehydrogenase named specifically for its oxidation role?

<p>The main reaction is oxidation of isocitrate to produce NADH. (C)</p> Signup and view all the answers

What is the primary function of fumarase in the Kreb cycle?

<p>Convert fumarate to malate (C)</p> Signup and view all the answers

Which product is formed in the final reaction of the citric acid cycle?

<p>Oxaloacetate (A)</p> Signup and view all the answers

How many molecules of NADH & H+ are produced per cycle of the citric acid cycle?

<p>3 (B)</p> Signup and view all the answers

Which of the following is NOT a major regulatory step in the Kreb cycle?

<p>Succinate Dehydrogenase (B)</p> Signup and view all the answers

What type of enzyme is fumarase classified as?

<p>Lyase (B)</p> Signup and view all the answers

In terms of energy yield, how many GTP (ATP equivalents) are produced per glucose molecule in the Kreb cycle?

<p>2 (B)</p> Signup and view all the answers

Which enzyme serves as the 'gatekeeper' for the Kreb cycle?

<p>Pyruvate Dehydrogenase (C)</p> Signup and view all the answers

What happens to all steps during the Kreb cycle where CO2 is released?

<p>They are regulated primarily by energy load (A)</p> Signup and view all the answers

Flashcards

Kreb Cycle

A metabolic cycle that breaks down food molecules into carbon dioxide, regenerating the starting molecule.

Acetyl group

A two-carbon molecule added to oxaloacetate to begin the Krebs Cycle.

Oxaloacetate

A small molecule that acts as a starting point and regenerating product in the Krebs Cycle.

8 metabolic reactions

The number of steps involved in completely oxidizing food molecules in the Kreb Cycle.

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Citrate Synthase

Enzyme responsible for the initial reaction to combine acetyl group with oxaloacetate. Starts the cycle.

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Carbon Dioxide Release

Two carbon atoms from the original acetyl group are released during the Kreb Cycle.

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Oxaloacetate Regeneration

Part of the Kreb Cycle where the starting molecule oxaloacetate is recreated.

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Metabolic Cycle

A cycle where the starting metabolite is regenerated in the process.

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Isocitrate Dehydrogenase

An enzyme in the citric acid cycle that catalyzes both the oxidation and decarboxylation of isocitrate to alpha-ketoglutarate.

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What is the product of isocitrate dehydrogenase action?

The reaction catalyzed by isocitrate dehydrogenase produces alpha-ketoglutarate, CO2, and NADH.

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Cofactors for isocitrate dehydrogenase

Isocitrate dehydrogenase requires NAD+ and Mg2+ as cofactors for its catalytic activity.

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What is the role of NAD+ in isocitrate dehydrogenase?

NAD+ acts as an oxidizing agent, accepting electrons and a proton from isocitrate during the dehydrogenase step.

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What happens in the decarboxylation step of isocitrate dehydrogenase?

The decarboxylation step releases CO2 from isocitrate, forming an alkene intermediate stabilized by Mg2+.

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Importance of Mg2+ in decarboxylation

Mg2+ stabilizes the carbonyl and carboxylic acid groups in isocitrate, facilitating the decarboxylation reaction.

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Why is isocitrate dehydrogenase named after oxidation?

Despite having decarboxylase activity, the enzyme is named for its crucial role in oxidizing isocitrate.

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What happens to the proton released by NAD+?

The proton released when NADH exits the active site is taken up by an acidic residue in the active site of isocitrate dehydrogenase.

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Alpha-Ketoglutarate Dehydrogenase (KGDH)

An enzyme complex that catalyzes the fourth step of the Krebs Cycle, converting alpha-ketoglutarate to succinyl-CoA.

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KGDH Mechanism

KGDH utilizes a similar mechanism to the Pyruvate Dehydrogenase (PDH) complex, involving a series of steps including decarboxylation, oxidation, and transfer of the succinyl group to CoA.

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Succinyl-CoA

A four-carbon molecule produced by the KGDH reaction in the Krebs Cycle, which serves as a key link to other metabolic pathways.

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CoASH

A coenzyme that plays a crucial role in the KGDH reaction, acting as a carrier of the succinyl group.

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TPP (Thiamine Pyrophosphate)

A cofactor used by KGDH, playing a vital role in the decarboxylation of alpha-ketoglutarate.

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Lipoamide

A cofactor used by KGDH and PDH, involved in the transfer of the succinyl group to CoA.

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FAD (Flavin Adenine Dinucleotide)

A cofactor used by KGDH, essential for the oxidation of lipoamide during the reaction.

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Fumarase

An enzyme that catalyzes the reversible hydration of fumarate to malate in the Krebs cycle. It adds water to the double bond of fumarate.

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Malate Dehydrogenase

An enzyme in the Krebs cycle that oxidizes malate to oxaloacetate, generating NADH and H+.

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Energy Yield per Krebs Cycle

One turn of the Krebs cycle produces 3 NADH, 1 FADH2, and 1 GTP (equivalent to ATP).

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Energy Yield per Glucose

Two cycles of the Krebs cycle per glucose molecule produce 6 NADH, 2 FADH2, and 2 GTP.

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Regulation of the Krebs Cycle

The activity of the Krebs cycle is primarily controlled by three key enzymes: pyruvate dehydrogenase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase.

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Pyruvate Dehydrogenase

An enzyme that catalyzes the decarboxylation and oxidation of pyruvate to acetyl-CoA, serving as the 'gatekeeper' of the Krebs cycle.

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Alpha-ketoglutarate Dehydrogenase

An enzyme that catalyzes the decarboxylation and oxidation of alpha-ketoglutarate to succinyl-CoA, generating NADH and H+.

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Succinyl-CoA Synthetase

An enzyme that generates GTP (ATP equivalent) through the phosphorylation of GDP. It also releases Coenzyme A and forms succinate.

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Succinate Dehydrogenase

An enzyme that catalyzes the oxidation of succinate to fumarate. It is embedded in the mitochondrial membrane and directly links the citric acid cycle to the electron transport chain.

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FAD in Succinate Dehydrogenase

Flavin adenine dinucleotide (FAD) is a coenzyme that acts as an electron acceptor in succinate dehydrogenase, accepting hydrogen atoms from succinate.

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Succinate Dehydrogenase and ETC

Succinate dehydrogenase is also Complex II in the electron transport chain, directly transferring the electrons harvested from succinate into the ETC.

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Transferring Electrons from FADH2

In the citric acid cycle, succinate dehydrogenase transfers electrons from FADH2, which is generated from succinate oxidation, to the ETC.

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Complex II

Succinate dehydrogenase is also known as Complex II in the ETC, showcasing its direct involvement in the electron transport chain.

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Citric Acid Cycle

A series of metabolic reactions that occur in the mitochondria, where acetyl-CoA is oxidized to carbon dioxide, producing ATP and reducing equivalents (NADH and FADH2).

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What is the starting molecule of the citric acid cycle?

Oxaloacetate, a four-carbon molecule, combines with acetyl-CoA (two-carbon) to start the cycle.

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What is the role of citrate synthase in the citric acid cycle?

Citrate synthase catalyzes the first reaction of the citric acid cycle, combining oxaloacetate with acetyl-CoA to form citrate.

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What is isocitrate?

An isomer of citrate, produced by the enzyme aconitase. Isocitrate is then oxidized and decarboxylated by isocitrate dehydrogenase, yielding alpha-ketoglutarate.

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What is the role of isocitrate dehydrogenase?

Isocitrate dehydrogenase catalyzes the oxidation and decarboxylation of isocitrate to alpha-ketoglutarate, producing NADH and CO2.

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What is alpha-ketoglutarate dehydrogenase complex?

A multienzyme complex that catalyzes the oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA, generating NADH and CO2. It also utilizes cofactors like thiamine pyrophosphate (TPP), lipoamide, and FAD.

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What is the role of succinyl-CoA synthetase?

Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate, generating GTP (equivalent to ATP) and releasing CoA.

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What is the purpose of the electron transport chain?

The electron transport chain (ETC) is a series of protein complexes embedded in the inner mitochondrial membrane that utilizes the reducing equivalents (NADH and FADH2) produced in the citric acid cycle to generate a proton gradient that drives ATP production.

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Study Notes

The Krebs Cycle

  • The Krebs Cycle, also known as the Citric Acid Cycle or Tricarboxylic Acid Cycle, is a central metabolic pathway.
  • It plays a critical role in energy production and biosynthesis.
  • The cycle completes the breakdown of sugars, started in glycolysis, and fuels ATP production.
  • It also serves as a central hub for biosynthetic reactions, creating intermediates for amino acid and other molecule building.
  • The cycle consists of 8 metabolic reactions, fully oxidizing food molecules to carbon dioxide.

Krebs Cycle Overview

  • The Krebs Cycle's 8 reactions use oxaloacetate as a starting point.
  • An acetyl group is added to oxaloacetate, initiating the cycle.
  • In a series of eight steps, the acetyl group is completely broken down.
  • The oxaloacetate is regenerated, allowing the cycle to repeat.
  • The cycle does not directly remove just two carbon atoms, but involves a careful shuffling of atoms.
  • Two carbons that originally belonged to oxaloacetate are released as carbon dioxide.
  • The original acetate atoms are rearranged to recreate oxaloacetate.

Krebs Cycle Reactions

  • The cycle involves 8 major reactions.
  • It's a metabolic cycle, meaning it regenerates the initial molecule, oxaloacetate.

Reaction 1: Citrate Synthase

  • The first reaction combines oxaloacetate and acetyl-CoA to form citrate.
  • Coenzyme A is released in the process.
  • The carboxylic acid groups in citrate originate from oxaloacetate, while the acetate-derived group and methyl groups are in red.

Reaction 2: Aconitase

  • Aconitase catalyzes the isomerization of citrate to isocitrate.
  • An intermediate named cis-aconitate forms during the reaction.
  • This step is often omitted in diagrams of the cycle.

Reaction 3: Isocitrate Dehydrogenase

  • Isocitrate is oxidized and decarboxylated to α-ketoglutarate.
  • Carbon dioxide is released.
  • NADH is produced.
  • Key cofactor: NAD+.

Reaction 4: α-Ketoglutarate Dehydrogenase

  • A very similar mechanism to the PDH Complex occurs.
  • Carbon dioxide is released and NADH is also formed.
  • This forms succinyl-CoA.

Reaction 5: Succinyl-CoA Synthetase

  • This creates GTP (a molecule equivalent to ATP) through GDP phosphorylation, releasing coenzyme A in the process.
  • This creates succinate.

Reaction 6: Succinate Dehydrogenase

  • This enzyme oxidizes succinate to form fumarate.
  • FAD is involved as an electron carrier, producing FADH2.
  • It is part of the electron transport chain.

Reaction 7: Fumarase

  • This lyase (enzyme) converts fumarate to malate, via the addition of water.

Reaction 8: Malate Dehydrogenase

  • Malate is oxidized to oxaloacetate, generating NADH.
  • Oxaloacetate is regenerated, thus completing the Krebs Cycle.

Energy Yield

  • In one turn of the cycle, 3 NADH/H+, 1 FADH2, and 1 GTP (equivalent to ATP) are produced.
  • For a glucose molecule, which is split into two acetyl-CoA, 6 pairs of NADH and two pairs of FADH2 are generated.
  • For each glucose molecule, two turns of the Krebs Cycle yield 2 GTP (ATP equivalents), 6 NADH/H+ and 2 FADH2.

Regulation of the Krebs Cycle

  • Several major dehydrogenase enzymes regulate this pathway, including pyruvate dehydrogenase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase.
  • They are highly sensitive to the energy levels within the cell.
  • High NADH or ATP, for example, results in inactivation as part of negative feedback.

Beriberi

  • Thiamine deficiency (Vitamin B1) leads to inefficient TPP coenzyme production.
  • This results in impaired function of PDH and α-ketoglutarate dehydrogenase.
  • Symptoms include weight loss, emotional disturbances, sensory/limb weakness, and irregular heartbeat.

Electron Transport Chain

  • The next stage uses the electrons harvested from the Krebs Cycle in the mitochondrial electron transport chain to produce ATP.

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Description

Explore the intricacies of the Krebs Cycle, also known as the Citric Acid Cycle, a vital metabolic pathway in energy production and biosynthesis. This quiz covers the eight metabolic reactions involved in the cycle, how it utilizes oxaloacetate, and its role in ATP production. Test your understanding of its function and significance in cellular respiration.

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