Oxidative Phosphorylation Overview

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Questions and Answers

Where does the citric acid cycle primarily take place?

  • In the nucleus
  • In the mitochondria (correct)
  • In the cytoplasm
  • In the endoplasmic reticulum

Which of the following is NOT a type of electron carrier found in the electron-transport chain complexes?

  • Flavin mononucleotide (FMN)
  • Iron-sulfur clusters
  • Nicotinamide adenine dinucleotide (NAD) (correct)
  • Cytochromes

What is the primary function of coenzyme Q (ubiquinone) in the electron transport chain?

  • To transport protons across the membrane
  • To accept electrons and transfer them between complexes (correct)
  • To synthesize ATP directly
  • To provide hydrogen for the citric acid cycle

Which deficiency is associated with a lack of hydride ion transfer?

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

What is the impact when ubiquinone accepts two electrons?

<p>It becomes ubiquinol and picks up two protons (D)</p> Signup and view all the answers

What is the main purpose of oxidative phosphorylation in cellular respiration?

<p>Synthesis of ATP (B)</p> Signup and view all the answers

What is the significance of the proton gradient in oxidative phosphorylation?

<p>It drives the phosphorylation of ADP (C)</p> Signup and view all the answers

What role does the inner membrane of mitochondria play?

<p>It is where the electron transport chain complexes are located (D)</p> Signup and view all the answers

Which of the following statements about the outer membrane of mitochondria is true?

<p>It allows the passage of metabolites (A)</p> Signup and view all the answers

What did Peter Mitchell contribute to the understanding of oxidative phosphorylation?

<p>He proposed the chemiosmotic theory (C)</p> Signup and view all the answers

How is energy released by electron transport utilized in oxidative phosphorylation?

<p>To establish a proton gradient (B)</p> Signup and view all the answers

What would happen if the membranes involved in chemiosmotic energy coupling were not present?

<p>ATP synthesis would cease (C)</p> Signup and view all the answers

Which compartment of the mitochondrion has a higher concentration of protons?

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

What is the primary function of Cytochromes in the electron transport chain?

<p>To act as one-electron carriers based on the Fe3+/Fe2+ redox system (B)</p> Signup and view all the answers

Which of the following statements about iron-sulfur proteins is true?

<p>They are based on the Fe3+/Fe2+ redox system and can be coordinated by cysteines. (A)</p> Signup and view all the answers

What role does the chemiosmotic model play in ATP synthesis?

<p>It creates a proton-motive force through electron transport. (A)</p> Signup and view all the answers

Which enzyme complex identified in the mitochondrial respiratory chain has the highest mass?

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

How does the number of subunits in the human cytochrome c compare to that of other complexes?

<p>It consists of only 1 subunit. (C)</p> Signup and view all the answers

What is the primary prosthetic group found in Succinate dehydrogenase?

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

Which components are part of the prosthetic groups in Ubiquinone: cytochrome c oxidoreductase?

<p>Hemes and Fe-S (A)</p> Signup and view all the answers

What distinct feature is observed in the structure of iron-sulfur clusters?

<p>They consist of an equal number of iron and sulfur atoms. (D)</p> Signup and view all the answers

What effect does the addition of cyanide (CN-) have on cellular respiration?

<p>It blocks electron transfer and inhibits respiration and ATP synthesis. (A)</p> Signup and view all the answers

How do venturicidin and oligomycin affect ATP synthesis?

<p>They block both ATP synthesis and respiration. (A)</p> Signup and view all the answers

What is the primary function of uncouplers like dinitrophenol (DNP)?

<p>To allow respiration to occur without ATP synthesis. (A)</p> Signup and view all the answers

What role does valinomycin play in mitochondrial function?

<p>It acts as an uncoupler by disrupting ion gradients. (B)</p> Signup and view all the answers

What physiological role does thermogenin play in brown adipose tissue?

<p>It generates heat through proton flow. (A)</p> Signup and view all the answers

What is the result of using the malate-aspartate shuttle in the liver, kidneys, and heart?

<p>It transports reducing equivalents from cytosol to mitochondrial matrix. (A)</p> Signup and view all the answers

How does the glycerol-3-phosphate shuttle differ from the malate-aspartate shuttle?

<p>It is primarily used in skeletal muscle and the brain. (A)</p> Signup and view all the answers

What is a consequence of the proton gradient established across the mitochondrial membrane?

<p>It is crucial for driving ATP synthesis. (B)</p> Signup and view all the answers

What triggers the activation of caspases during apoptosis?

<p>Release of cytochrome c in the cytosol (C)</p> Signup and view all the answers

What is the inheritance pattern of mitochondrial DNA?

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

Which of the following is primarily synthesized in the cytosol and then imported into the mitochondria?

<p>Mitochondrial enzymes (C)</p> Signup and view all the answers

What condition is characterized by defects in oxidative phosphorylation leading to low ATP levels?

<p>Mitochondrial diabetes (C)</p> Signup and view all the answers

What is the primary measure of the energy status of a cell during oxidative phosphorylation?

<p>The concentration of ADP (B)</p> Signup and view all the answers

How is the proton motive force created in mitochondria?

<p>By the transfer of electrons through the electron transport chain (D)</p> Signup and view all the answers

Which is one of the key roles of ribosomes found in mitochondria?

<p>Synthesis of mitochondrial proteins (D)</p> Signup and view all the answers

Which compound is produced during the conversion of pyruvate to acetyl-CoA?

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

What is the primary function of ATP in the cell?

<p>To act as an energy currency (C)</p> Signup and view all the answers

What is the total ATP yield when using the Malate Shuttle?

<p>38 ATP (B)</p> Signup and view all the answers

Which process is directly linked to the failure of mitochondria in insulin release?

<p>Low ATP levels due to oxidative phosphorylation defects (B)</p> Signup and view all the answers

How is the rate of ATP synthesis primarily regulated during oxidative phosphorylation?

<p>By the availability of NADH and ADP/Pi (A)</p> Signup and view all the answers

Which of the following correctly describes the effect of high ATP concentrations on oxidative phosphorylation?

<p>Inhibits oxidative phosphorylation (D)</p> Signup and view all the answers

What is the role of the Mass-Action Ratio in ATP synthesis?

<p>To stabilize ATP production relative to energy needs (C)</p> Signup and view all the answers

Which intermediate is derived from citrate during the Krebs cycle?

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

What is the outcome of the reaction catalyzed by FAD in the Krebs cycle?

<p>Production of FADH2 (C)</p> Signup and view all the answers

Flashcards

Matrix location in cellular respiration

The matrix is the location within mitochondria where the citric acid cycle and parts of lipid and amino acid metabolism take place.

Electron carriers in ETC

Electron-transport chain complexes contain different molecules that carry electrons, including flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), cytochromes, and iron-sulfur clusters.

Coenzyme Q's role

Coenzyme Q, also known as ubiquinone, is a lipid-soluble electron carrier that transports electrons from complexes I and II to complex III.

Electron transfer order

Electron transfer in the electron transport chain is governed by reduction potentials; molecules with a higher tendency to accept electrons are reduced first.

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Coenzyme function

Coenzymes are molecules associated with dehydrogenases and transfer hydride ions (H-) or hydrogen atoms (H) in redox reactions.

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Oxidative Phosphorylation

The process where energy from NADH and FADH2 is used to produce ATP.

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Chemiosmotic Theory

Energy released from electron transport is used to pump protons against their gradient, creating a stored energy source to fuel ATP synthesis.

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ATP Synthesis

The process of creating ATP from ADP and inorganic phosphate (Pi).

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Mitochondrial Membranes

The inner and outer membranes of mitochondria are critical for creating and maintaining a proton gradient needed for ATP production.

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Electron Transport Chain Complexes

Protein complexes embedded in the inner mitochondrial membrane that facilitate the transfer of electrons and the pumping of protons.

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Reduced Cofactors

Electron carriers like NADH and FADH2, which are formed during the breakdown of fuels.

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Mitochondrial Compartments

The mitochondria has four sections (outer membrane, intermembrane space, inner membrane, and matrix) each with a specific function.

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Proton Gradient

A difference in proton concentration across a membrane. This gradient stores energy that drives ATP synthesis.

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Cytochromes

One-electron carriers that use the Fe3+/Fe2+ redox system, with heme derivatives.

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Iron-Sulfur Proteins

One-electron carriers using the Fe3+/Fe2+ redox system, coordinated by cysteines in proteins or in iron-sulfur clusters.

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Chemiosmotic Model

Electron transport in complexes creates a proton gradient (proton-motive force) used to drive ATP synthesis.

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Proton-motive force

A concentration gradient of protons generated by electron transport in complexes, used to drive ATP production.

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NADH dehydrogenase

Enzyme complex I in the mitochondrial respiratory chain, involved in electron transfer.

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Succinate dehydrogenase

Enzyme complex II in the mitochondrial respiratory chain, transferring electrons from succinate.

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Cytochrome c oxidoreductase

Enzyme complex III participating in the electron transfer chain between Fe-S and cytochrome c.

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Cytochrome oxidase

Enzyme complex IV, final electron acceptor in the electron transfer chain.

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Cyanide & Respiration

Cyanide blocks electron transfer in Complex IV (cytochrome oxidase), halting both respiration and ATP synthesis.

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Succinate & ATP Synthesis

Mitochondria supplied with succinate respire and synthesize ATP only when ADP and Pi are present. Inhibiting ATP synthase blocks both processes.

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Dinitrophenol: ATP Uncoupler

DNP acts as an uncoupler, allowing respiration to continue without ATP synthesis. It disrupts the proton gradient.

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Ionophores: Gradient Disruption

Ionophores, like valinomycin, disrupt ion gradients across membranes, uncoupling electron transport and ATP synthesis.

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Artificial Gradient & ATP Synthesis

Adding K+ artificially creates an electrochemical gradient that can drive ATP synthesis even without a substrate, proving the crucial role of proton gradients.

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Thermogenin: Heat Production

Thermogenin, found in brown fat, is an uncoupling protein that allows H+ flow, generating heat. Important for babies and hibernating animals.

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Malate-Aspartate Shuttle

This shuttle transports reducing equivalents (NADH) from the cytosol into the mitochondrial matrix, mainly in liver, kidneys, and heart.

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Glycerol-3-Phosphate Shuttle

This alternative shuttle moves reducing equivalents from cytosol to the mitochondrial matrix, prevalent in skeletal muscle and brain.

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What is the role of ADP in Oxidative Phosphorylation?

ADP, along with inorganic phosphate (Pi), serves as the primary acceptor of energy released from the electron transport chain in Oxidative Phosphorylation. The concentration of ADP reflects the cell's energy needs, regulating the rate of ATP production.

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What is the Mass-Action Ratio?

The Mass-Action Ratio ([ATP]/[ADP][Pi]) indicates the cell's energy state. A high ratio indicates high energy reserves, while a low ratio signals the need for ATP production.

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How does high ATP regulate Oxidative Phosphorylation?

High ATP levels act as an inhibitor at multiple points in the Oxidative Phosphorylation process, slowing down ATP production when energy demand is low. This ensures efficient energy utilization.

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What happens when Oxidative Phosphorylation is inhibited?

Inhibition of Oxidative Phosphorylation results in an accumulation of NADH, as the electron transport chain is stalled. This signifies a decrease in the overall energy production of the cell.

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How is Oxidative Phosphorylation regulated?

The rate of Oxidative Phosphorylation is primarily regulated by the availability of substrates, particularly NADH and ADP, which act as signals for energy demand.

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What is the relationship between Oxidative Phosphorylation and ATP synthesis?

Oxidative Phosphorylation is the process that fuels ATP synthesis. The energy released during electron transport is captured by the proton gradient, which then drives ATP synthesis.

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What is the significance of the proton gradient in Oxidative Phosphorylation?

The proton gradient, established across the mitochondrial membrane during electron transport, represents a stored energy source. This energy is released when protons flow back through ATP synthase, driving ATP production.

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How does the electron transport chain contribute to ATP production?

The electron transport chain, by moving electrons across the inner mitochondrial membrane, pumps protons against their concentration gradient. This proton gradient is used by ATP synthase to synthesize ATP.

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Feedback Inhibition in Glycolysis

A regulatory mechanism where high levels of ATP and citrate (a citric acid cycle intermediate) inhibit the enzyme phosphofructokinase-1 (PFK-1), the rate-limiting step in glycolysis.

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Mitochondria's Role in Apoptosis

Mitochondria play a critical role in programmed cell death by releasing cytochrome c into the cytosol, triggering the activation of caspases, a family of proteases that dismantle cellular components.

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Mitochondrial DNA inheritance

Mitochondrial DNA (mtDNA) is inherited maternally, meaning it is passed down from mother to offspring.

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Mitochondrial Gene Expression

Mitochondria possess their own ribosomes for protein synthesis within the organelle, but most mitochondrial proteins are encoded by nuclear DNA, synthesized in the cytosol, and then imported into the mitochondria.

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Mitochondrial Diabetes

Defects in oxidative phosphorylation within mitochondria can lead to a rare form of diabetes because low ATP levels in the cell prevent insulin release.

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Chemiosmotic Theory & Mitochondria

This theory explains how energy from electron transport is used to create a proton gradient across the inner mitochondrial membrane, which is then used to drive ATP synthesis.

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Electron Carriers in Oxidative Phosphorylation

Oxidative phosphorylation uses electron carriers like NADH and FADH2, which transfer electrons through a series of protein complexes embedded in the inner mitochondrial membrane.

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ATP Production and Uncoupling

Electron flow and ATP production are tightly coupled, but uncouplers can disrupt this coupling, dissipating the proton gradient and reducing ATP synthesis.

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Study Notes

Oxidative Phosphorylation Overview

  • Oxidative phosphorylation harnesses energy from NADH and FADH₂ to produce ATP.
  • Carbohydrates, lipids, and amino acids are the primary reduced fuels for the cell.
  • Electrons from reduced fuels are transferred to NADH or FADH₂ cofactors.

Chemiosmotic Theory

  • Energy needed to phosphorylate ADP comes from protons flowing down an electrochemical gradient.
  • ΔG is directly related to ΔE = Eo (e⁻ acceptor) – Eo (e⁻ donor).
  • ΔG = - ηIΔE, where T = 298°K = 25°C, R = 8.315 J/mol·K, η = # electrons transferred per molecule, J = 96.48 kJ/V·mol (Faraday).

Chemiosmotic Energy Coupling

  • Proton gradient needed for ATP synthesis is established across membranes impermeable to ions.
  • These include the plasma membrane in bacteria, inner membrane in mitochondria, and thylakoid membrane in chloroplasts.
  • Membranes must contain proteins to couple electron flow (downhill) with proton flow (uphill) across the membrane.
  • A protein couples the downhill flow of protons to the phosphorylation of ADP.

Structure of Mitochondrion

  • Double membrane creates four distinct compartments:
    • Outer membrane: relatively porous, permeable to small molecules.
    • Intermembrane space (IMS): Similar environment to cytosol, with higher proton concentration (lower pH).
    • Inner membrane: Impermeable, with proton gradient across it. Contains complexes of electron transport chain and cristae to increase surface area.
    • Matrix: Contains citric acid cycle enzymes, fatty acid oxidation enzymes, amino acid oxidation enzymes, DNA, ribosomes, etc. Lower proton concentration (higher pH).

Electron Transport Chain Complexes

  • Each complex contains multiple redox centers, including flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD), cytochromes (a, b, or c), and iron-sulfur clusters.
  • Electron transfer order depends on reduction potential.

Coenzymes as Electron Carriers

  • Coenzymes associated with dehydrogenases transfer hydride ions (H⁻, one proton plus two electrons).
  • NAD+/NADH, FMN/FMNH₂, FAD/FADH₂ are important coenzymes.

Coenzyme Q (Ubiquinone)

  • Lipid-soluble quinone isoprenoid compound, readily accepting electrons from different redox-active compounds.
  • Accepts two electrons, picks up two protons to become ubiquinol.
  • Freely diffuses, carrying electrons with protons across the membrane.
  • Mobile electron carrier, transporting electrons from Complexes I and II to Complex III.

Cytochromes

  • Composed of Fe³⁺/Fe²⁺ redox system and heme derivatives (a, b, or c). Ring additions/substitutions affect redox properties.
  • One-electron carriers.

Iron-Sulfur Proteins

  • One-electron carriers based on Fe³⁺/Fe²⁺ redox system.
  • Iron ions coordinated by cysteine in proteins or as iron-sulfur clusters.
  • Iron-sulfur clusters have equal numbers of iron and sulfur atoms.

Chemiosmotic Model for ATP Synthesis

  • Electron transport through complexes I-IV creates a proton-motive force (proton gradient).
  • Energy of proton-motive force drives ATP synthesis.

Mitochondrial ATP Synthase Complex

  • Composed of two functional units, Fo and F₁.
    • Fo is the integral membrane complex that transports protons dissipating the proton gradient.
    • F₁ is the soluble complex in matrix catalyzing ATP hydrolysis and creation.
  • Dimers exist in different conformations (open, loose, tight).

Synthesis of ATP in ATP Synthase

  • Translocation of three protons fuels synthesis of one ATP.

Inhibitors

  • Cyanide (CN⁻), carbon monoxide, antimycin A, myxothiazol, rotenone, amytal, piericidin A, DCMU, oligomycin, venturicidin, DCCD, FCCP, DNP, valinomycin, and atractyloside interfere with the process.

Transport of Different Species in/Out of Matrix

  • Proton translocation facilitates cotransport of substrates into and products out of the mitochondria.

Malate-Aspartate Shuttle

  • This shuttle transports reducing equivalents (NADH) from cytosol into the mitochondrial matrix.

Glycerol-3-Phosphate Shuttle

  • An alternative mechanism for shuttling reducing equivalents (NADH) from cytosol to the mitochondrial matrix. This process results in the formation of FADH₂, rather than NADH, resulting in a lower energy yield (1 ATP less per NADH)

Regulation of Oxidative Phosphorylation

  • Primarily regulated by substrate availability (NADH and ADP/Pi).
  • Rate of O₂ consumption regulated by the amount of ADP/Pi.
  • High ATP levels cause feedback inhibition Cascade up to PFK-1.

Mitochondria and Apoptosis

  • Loss of mitochondrial membrane integrity releases cytochrome c, initiating apoptosis (programmed cell death).

Mitochondrial Genetics

  • Mitochondrial DNA is circular and encodes rRNA, tRNA, and enzymes of central metabolism.
  • Mitochondria have their own ribosomes for protein synthesis.
  • Mitochondrial DNA is maternally inherited.

Mitochondrial Mutations and Diabetes

  • Defects in oxidative phosphorylation result in low ATP, inhibiting correct insulin release from pancreatic β cells.

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