Cellular Respiration Quiz
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Questions and Answers

Which disorder is characterized by progressive neurodegeneration and lactic acidosis episodes?

  • Parkinson's
  • MELAS (correct)
  • Leber hereditary optic neuropathy
  • Cardiomyopathies

    • What is the main cause of Leber hereditary optic neuropathy (LHON)?

  • Mitochondrial inheritance (correct)
  • Nutritional deficiencies
  • Environmental factors
  • Viral infections

    • What primarily leads to sudden blindness in patients with LHON?

  • Glaucoma
  • Cataracts
  • Age-related macular degeneration
  • Retinal detachment (correct)

    • How does ATP synthesis occur within the electron transport chain?

    <p>By generating a proton gradient</p> Signup and view all the answers

    Which component is NOT part of the electron transport chain that may be mutated in LHON?

    <p>ATP synthase</p> Signup and view all the answers

    Which of the following is an exogenous uncoupler?

    <p>Pentachlorophenol</p> Signup and view all the answers

    What is a potential consequence of aspirin overdose?

    <p>Fever</p> Signup and view all the answers

    Which vitamin deficiency is linked to severe lethargy in mitochondrial function?

    <p>Vitamin B2</p> Signup and view all the answers

    Which complex does Rotenone inhibit?

    <p>Complex I</p> Signup and view all the answers

    Which of the following conditions is related to excess free fatty acids?

    <p>Hyperthyroidism</p> Signup and view all the answers

    What does oligomycin inhibit in mitochondrial function?

    <p>ATP synthase</p> Signup and view all the answers

    Mitochondrial diseases typically affect which of the following tissues the most?

    <p>Nervous tissue</p> Signup and view all the answers

    Which of the following can inhibit ATP synthesis and lead to cell death?

    <p>Inhibition of any complex of the ETC</p> Signup and view all the answers

    What is the primary function of the electron transport chain (ETC)?

    <p>To convert energy from electrons into ATP</p> Signup and view all the answers

    Where is the electron transport chain located within the mitochondrion?

    <p>In the inner mitochondrial membrane</p> Signup and view all the answers

    What role do NADH and FADH2 play in ATP synthesis?

    <p>They donate electrons to the electron transport chain.</p> Signup and view all the answers

    What happens to the energy not converted into ATP in the ETC?

    <p>It is utilized to transport Ca2+ and generate heat.</p> Signup and view all the answers

    Which coenzyme is produced during the conversion of 2H+ and 2e- by NAD+?

    <p>NADH</p> Signup and view all the answers

    What is the role of oxygen in the electron transport chain?

    <p>It functions as an avid electron acceptor.</p> Signup and view all the answers

    What is formed as protons are pumped across the inner mitochondrial membrane?

    <p>A proton gradient</p> Signup and view all the answers

    How many protons are required to generate one molecule of ATP according to the content?

    <p>4</p> Signup and view all the answers

    What is the function of ATP synthase?

    <p>To synthesize ATP from the energy of H+ movement.</p> Signup and view all the answers

    Which statement is true regarding the proton motive force?

    <p>It refers to the potential energy stored in a proton gradient.</p> Signup and view all the answers

    In the chemiosmotic hypothesis, what is the first step of ATP generation?

    <p>Protons are pumped from the mitochondrial matrix to the intermembranous space.</p> Signup and view all the answers

    What complex is specifically referred to as the F0 unit of ATP synthase?

    <p>The unit that forms the proton channel.</p> Signup and view all the answers

    Which of the following describes NADH's role in the electron transport chain?

    <p>It donates electrons to the electron transport chain.</p> Signup and view all the answers

    What is transported in exchange for ATP?

    <p>ADP</p> Signup and view all the answers

    Which shuttle transfers electrons from cytosolic NADH to mitochondrial FAD?

    <p>Glycerol 3-phosphate shuttle</p> Signup and view all the answers

    What is the role of the Electron Transport Chain (ETC) in cellular respiration?

    <p>Combine electrons and hydrogens to form water</p> Signup and view all the answers

    Which component of the ETC is a mobile carrier within the lipid bilayer?

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

    Which component is NOT a large protein complex within the ETC?

    <p>Coenzyme Q</p> Signup and view all the answers

    Which electrons are specifically transported into the mitochondrion?

    <p>Electrons from cytosolic NADH</p> Signup and view all the answers

    What do the respiratory chain components of the ETC do?

    <p>Accept and donate electrons to mobile carriers</p> Signup and view all the answers

    What is one of the key functions of substrates shuttles?

    <p>Permit passage of specific molecules from cytosol to mitochondrial matrix</p> Signup and view all the answers

    What is a notable feature of MELAS syndrome?

    <p>Characterized by episodes of lactic acidosis</p> Signup and view all the answers

    Leber hereditary optic neuropathy (LHON) predominantly affects which demographic?

    <p>Males in their 20s and 30s</p> Signup and view all the answers

    Which electron transport chain component is most commonly mutated in LHON?

    <p>NADH-Q reductase</p> Signup and view all the answers

    What consequence does impaired electron flow through the respiratory chain lead to in LHON?

    <p>Visual field defects</p> Signup and view all the answers

    In MELAS syndrome, what type of genetic material is found in cells?

    <p>Both mutant and wild-type mtDNA</p> Signup and view all the answers

    What is a consequence of high concentrations of bilirubin in infants?

    <p>Severe brain damage</p> Signup and view all the answers

    Which of the following substances acts as an exogenous uncoupler?

    <p>2,4 dinitrophenol</p> Signup and view all the answers

    What effect does oligomycin have on mitochondrial function?

    <p>Closes the H+ channel of ATP synthase</p> Signup and view all the answers

    Which vitamin deficiency is most closely associated with complications affecting the cardiovascular and nervous systems?

    <p>Vitamin B3</p> Signup and view all the answers

    What provides stimulation for thyroid hormones to activate mitochondrial respiration?

    <p>Sympathetic stimulation</p> Signup and view all the answers

    What is the primary function of NADH and FADH2 in the electron transport chain?

    <p>To provide electrons for ATP synthesis</p> Signup and view all the answers

    Which statement is true regarding the inhibition of Complex I in the electron transport chain?

    <p>It is inhibited by rotenone.</p> Signup and view all the answers

    In mitochondrial diseases, which tissues are most likely to be affected?

    <p>Nervous tissue and skeletal muscle</p> Signup and view all the answers

    Which of the following best describes the energy that is not converted into ATP during the electron transport chain process?

    <p>Wasted energy lost as heat and for calcium transport</p> Signup and view all the answers

    What role does ATP synthase play in the mitochondrion?

    <p>It catalyzes the synthesis of ATP from ADP and inorganic phosphate</p> Signup and view all the answers

    What is the primary role of excess free fatty acids in the context of uncoupling?

    <p>To activate mitochondrial respiration</p> Signup and view all the answers

    Where is the electron transport chain specifically located within the mitochondrion?

    <p>On the inner mitochondrial membrane</p> Signup and view all the answers

    What is required for electrons from NADH and FADH2 to reach the electron transport chain for ATP synthesis?

    <p>Transport proteins in the outer mitochondrial membrane</p> Signup and view all the answers

    What is the maximum number of ATP produced from one glucose molecule during aerobic respiration?

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

    What role do uncoupling proteins have in the mitochondria?

    <p>Create a proton leak</p> Signup and view all the answers

    What is the primary function of F0 rotation in ATP synthase?

    <p>Binding of ADP and Pi</p> Signup and view all the answers

    Which electron transport complex do electrons from FADH2 enter at?

    <p>Complex II</p> Signup and view all the answers

    What is one of the key products generated during glycolysis?

    <p>2 ATP</p> Signup and view all the answers

    What is thermogenin (UCP1) responsible for in brown adipose tissue?

    <p>Heat production</p> Signup and view all the answers

    Which shuttle system transfers electrons from cytosolic NADH to mitochondrial FAD?

    <p>Glycerol-Phosphate Shuttle</p> Signup and view all the answers

    How many ATP are generated per NADH during oxidative phosphorylation?

    <p>3 ATP</p> Signup and view all the answers

    What is transported in exchange for ATP during cellular respiration?

    <p>ADP</p> Signup and view all the answers

    Which shuttle transfers electrons from cytosolic NADH to mitochondrial NAD+?

    <p>Malate-aspartate shuttle</p> Signup and view all the answers

    What do the mobile carriers in the electron transport chain primarily do?

    <p>Donate and accept electrons</p> Signup and view all the answers

    Which component combines with electrons and hydrogens to form water in the electron transport chain?

    <p>Oxygen</p> Signup and view all the answers

    Which statement correctly describes the function of substrate shuttles?

    <p>They permit the passage of specific molecules from cytosol to mitochondrial matrix.</p> Signup and view all the answers

    What role does FAD play in the glycerol 3-phosphate shuttle?

    <p>It accepts electrons from cytosolic NADH.</p> Signup and view all the answers

    Which of the following molecules is NOT freely diffusible within the inner mitochondrial membrane?

    <p>NADH</p> Signup and view all the answers

    What happens to the electrons that are transported into the mitochondrion from cytosolic NADH?

    <p>They are transferred back to mitochondrial NAD+ or FAD.</p> Signup and view all the answers

    What is the final electron acceptor in the electron transport chain?

    <p>O2</p> Signup and view all the answers

    Which coenzymes are directly involved in donating electrons to the electron transport chain?

    <p>NADH and FADH2</p> Signup and view all the answers

    Which process best describes the mechanism through which ATP synthesis is coupled to the proton gradient?

    <p>Chemiosmosis</p> Signup and view all the answers

    What is one potential consequence of uncoupling in mitochondria?

    <p>Enhanced proton leakage and heat generation</p> Signup and view all the answers

    In the context of electron transport chain diseases, what is a common outcome of iron and vitamin deficiencies?

    <p>Defects in electron transport</p> Signup and view all the answers

    Which of the following are classified as endogenous uncouplers?

    <p>Bilirubin at high concentrations</p> Signup and view all the answers

    Which mechanism does excessive bilirubin cause damage in infants?

    <p>Causes kernicterus</p> Signup and view all the answers

    Which of the following is a consequence of complex IV inhibition?

    <p>Cell death due to energy depletion</p> Signup and view all the answers

    Which factor primarily influences the activation of mitochondrial respiration via thyroid hormones?

    <p>Sympathetic nervous stimulation</p> Signup and view all the answers

    What effect does a deficiency in vitamins B2 or B3 have on mitochondrial function?

    <p>Causes severe lethargy and complications</p> Signup and view all the answers

    What type of mutations lead to 'Oxphos' diseases?

    <p>Mutations in proteins of the various complexes</p> Signup and view all the answers

    Which of the following best describes the role of excess free fatty acids in mitochondrial function?

    <p>They act as endogenous uncouplers.</p> Signup and view all the answers

    What is the primary action of oligomycin in mitochondrial function?

    <p>Blocks the H+ channel of ATP synthase</p> Signup and view all the answers

    What is the maximum ATP yield from one molecule of glucose when using the malate-aspartate shuttle system?

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

    Which process is facilitated by uncoupling proteins in brown adipose tissue?

    <p>Proton leak generation</p> Signup and view all the answers

    What is the primary purpose of the energy released from electrons as they pass down the electron transport chain?

    <p>To pump protons across the inner mitochondrial membrane</p> Signup and view all the answers

    What is the primary reason humans have little brown fat compared to neonates?

    <p>Developmental changes</p> Signup and view all the answers

    Which electron carrier generates more ATP molecules per molecule due to its entry point in the electron transport chain?

    <p>NADH</p> Signup and view all the answers

    Which statement about the inner mitochondrial membrane is accurate?

    <p>It contains ATP synthase and is impermeable to protons</p> Signup and view all the answers

    What is the outcome when the inner mitochondrial membrane becomes more permeable due to certain compounds?

    <p>Decreased proton gradient</p> Signup and view all the answers

    What is the result of inadequate transport of NADH and FADH2 to the electron transport chain?

    <p>Reduced ATP synthesis and potential cellular energy crisis</p> Signup and view all the answers

    What function do coenzymes NAD+ and FAD serve in cellular respiration?

    <p>They accept electrons and protons during the breakdown of substrates</p> Signup and view all the answers

    Which of the following accurately describes the total ATP yield during the complete oxidation of glucose including oxidative phosphorylation steps?

    <p>Total yield is dependent on the electron transport chain efficiency.</p> Signup and view all the answers

    What significant role does thermogenin (UCP1) play in energy metabolism?

    <p>Generating heat through non-shivering thermogenesis</p> Signup and view all the answers

    Which of the following statements explains how the electron transport chain contributes to thermogenesis?

    <p>Some energy from the electron transport process is lost as heat rather than being converted to ATP</p> Signup and view all the answers

    What is the immediate effect of the electron transport chain's function on cellular metabolism?

    <p>Increased proton gradient leading to ATP synthesis</p> Signup and view all the answers

    What happens to the electrons from cytosolic NADH when they're transported into the mitochondrion?

    <p>They are transferred to an intermediate, which then transfers them to mitochondrial NAD+ or FAD.</p> Signup and view all the answers

    Which shuttle transfers electrons from cytosolic NADH to mitochondrial NAD+?

    <p>Malate-aspartate shuttle</p> Signup and view all the answers

    What is the primary role of substrate shuttles in cellular metabolism?

    <p>To permit the passage of specific molecules between cytosol and mitochondria.</p> Signup and view all the answers

    Which component of the electron transport chain is a freely diffusible carrier within the lipid bilayer?

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

    What is the relationship between the complexes I-IV and the electron transport chain?

    <p>They accept and donate electrons to mobile carriers.</p> Signup and view all the answers

    How is the energy from electron transfer in the electron transport chain ultimately utilized?

    <p>To pump protons across the inner mitochondrial membrane, creating a proton gradient.</p> Signup and view all the answers

    Which of the following correctly describes the function of the mobile carriers in the electron transport chain?

    <p>They receive electrons and transport them between protein complexes.</p> Signup and view all the answers

    What type of molecules lack a transport protein across the inner mitochondrial membrane?

    <p>NADH</p> Signup and view all the answers

    Study Notes

    Exogenous Uncouplers

    • 2,4-dinitrophenol and pentachlorophenol are examples of exogenous uncouplers.
    • Pentachlorophenol is a pesticide.
    • Aspirin overdose can lead to fever due to uncoupling.

    Endogenous Uncouplers

    • Bilirubin, at high concentrations, can cause severe brain damage in infants (kernicterus).
    • Excess free fatty acids, at high concentrations, can act as endogenous uncouplers.
    • Thyroid hormones (T3) can uncouple oxidative phosphorylation through various mechanisms, including:
      • Sympathetic stimulation
      • Increasing acylcarnitine production, which activates mitochondrial respiration.
      • Direct stimulation of uncoupling protein 1 (UCP1) transcription.

    Inhibition of ETC

    • Inhibition of any complex in the electron transport chain (ETC) inhibits ATP synthesis and can lead to cell death.
    • Doxorubicin inhibits the ETC at CoQ.
    • Rotenone, a poison, inhibits Complex I.
    • Cyanide and carbon monoxide inhibit Complex IV by competing with oxygen for binding.
    • Oligomycin inhibits ATP synthase by binding to the Fo domain, closing the proton channel.

    Deficiencies Affecting ETC

    • Iron deficiency inhibits any of the iron-containing complexes in the ETC.
    • Deficiencies in vitamin B2 (riboflavin) or B3 (niacin) can lead to severe lethargy and complications affecting various systems.
    • Niacin is a precursor for NAD, a coenzyme for Complex I.
    • Riboflavin is a precursor for FAD and FMN, and its deficiency inhibits Complex I.

    Mitochondrial Diseases

    • Mutations in genes encoding proteins of the ETC complexes can lead to "Oxphos" diseases.
    • These mutations can occur in either nuclear or mitochondrial DNA.
    • Tissues with high energy demand, such as nervous tissue, kidney, heart, and skeletal muscle, are often affected.
    • Examples of common disorders include:
      • Parkinson's disease
      • Cardiomyopathies
      • MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
    • MELAS is characterized by progressive neurodegeneration, repeated episodes of lactic acidosis and myopathy, and variable expression due to the presence of both mutant and wild-type mitochondrial DNA.

    Leber Hereditary Optic Neuropathy (LHON)

    • LHON is a mitochondrial disease caused by mutations in genes encoding subunits of NADH-Q reductase (Complex I), cytochrome c reductase (Complex III), or cytochrome oxidase (Complex IV).
    • It is inherited through the maternal line.
    • Males are affected four times more frequently than females.
    • LHON leads to sudden onset of blindness in young adults, typically in their 20s or 30s.
    • Bilateral central vision loss is caused by retinal detachment.

    Oxidative Phosphorylation

    • Electrons from NADH and FADH2 are transferred to the ETC.
    • Oxygen acts as the final electron acceptor.
    • As electrons move down through the ETC complexes, energy is released.
    • This energy is used to pump protons across the inner mitochondrial membrane, establishing a proton gradient.
    • Protons flow back into the mitochondrial matrix through ATP synthase, generating ATP.

    Chemiosmotic Hypothesis

    • This hypothesis describes how ATP generation is coupled to electron transport in the ETC.
    • It involves two steps:
      • Proton pumping from the mitochondrial matrix to the intermembrane space, creating a proton gradient.
      • Utilizing the proton gradient to drive ATP synthesis.

    Proton Motive Force

    • The proton gradient created by proton pumping across the inner mitochondrial membrane is known as the proton motive force.

    ATP Synthase

    • ATP synthase is a complex enzyme that facilitates the movement of protons back into the mitochondrial matrix.
    • It consists of two components:
      • Fo unit: An integral membrane protein containing the proton channel.
      • F1 unit: The ATP synthase enzyme.
    • Proton passage through the Fo unit causes rotation, driving ATP synthesis by the F1 unit.

    Energy Production and Utilization

    • Electrons passing down the ETC release energy used for ATP synthesis (oxidative phosphorylation).
    • Excess energy beyond that used for ATP production is utilized for functions like calcium transport and heat generation.

    Coenzymes

    • NAD+ and FAD are important coenzymes that carry electrons in the ETC.
    • NAD+ is reduced to NADH, and FAD is reduced to FADH2.
    • These reduced forms contain a lot of energy.

    Mitochondria

    • Mitochondria are organelles responsible for ATP production through oxidative phosphorylation.
    • They have two membranes:
      • The outer membrane is porous to small molecules.
      • The inner membrane is impermeable to most ions, small molecules, and large molecules.
    • The ETC is located in the inner mitochondrial membrane.
    • Glycolysis takes place in the cytoplasm, producing NADH.
    • NADH and FADH2 produced in glycolysis and the citric acid cycle must reach the ETC for ATP synthesis.

    Membrane Transport Systems

    • The inner mitochondrial membrane contains specific transport systems for various molecules, including ADP and Pi, which are required for ATP synthesis.
    • ADP is transported into the mitochondria in exchange for ATP.

    Substrate Shuttles

    • Substrate shuttles are transport proteins that mediate the passage of molecules from the cytosol to the mitochondrial matrix.
    • The inner mitochondrial membrane lacks an NADH transport protein, so substrate shuttles facilitate electron transport from cytosolic NADH to the ETC.
    • Two main shuttle systems exist:
      • Glycerol 3-phosphate shuttle: Transfers electrons from cytosolic NADH to mitochondrial FAD.
      • Malate-aspartate shuttle: Transfers electrons from cytosolic NADH to mitochondrial NAD+.

    Electron Transport Chain (ETC)

    • The ETC comprises protein complexes (I-IV) and mobile electron carriers (cytochrome c and CoQ).
    • Each ETC complex accepts and donates electrons to mobile carriers.
    • Electrons ultimately combine with oxygen and hydrogen to form water.
    • Mobile carriers include NADH (mitochondrial matrix), CoQ (ubiquinone), cytochrome c (peripheral membrane protein), and molecular oxygen.

    ETC Components

    • Most members of the ETC are large protein complexes, coupled to metal ions (e.g., iron).
    • Coenzyme Q is not a protein complex but rather a mobile electron carrier.

    Uncouplers

    • Exogenous uncouplers:
      • Increase the permeability of the inner mitochondrial membrane
      • Examples: 2,4 dinitrophenol, pentachlorophenol, aspirin overdose
    • Endogenous uncouplers:
      • Examples: bilirubin, excess free fatty acids, thyroid hormones (T3)
    • Uncoupling oxidative phosphorylation:
      • Energy is released as heat instead of being used for ATP synthesis
      • Leads to non-shivering thermogenesis in brown adipose tissue
      • Thermogenin (UCP1) is responsible for this heat production
      • Humans have little brown fat after infancy

    Electron Transport Chain (ETC)

    • Location: Inner mitochondrial membrane
    • Function:
      • Generates a proton gradient across the inner mitochondrial membrane
      • This gradient is used by ATP synthase to produce ATP
    • Components:
      • Protein complexes I-IV
      • Mobile carriers: Coenzyme Q and cytochrome c
      • Freely diffusible components: NADH, FADH2, molecular oxygen
    • Flow of electrons:
      • NADH and FADH2 donate electrons
      • Electrons pass through the complexes
      • Electrons are ultimately combined with oxygen to form water

    ATP Synthase

    • Location: Inner mitochondrial membrane
    • Function: Uses the proton gradient to produce ATP
    • Mechanism:
      • Protons flow through a channel in ATP synthase
      • This drives the rotation of a central rotor, which changes the conformation of ATP-binding sites
      • This allows ADP and Pi to bind and be converted to ATP

    Mitochondrial Diseases

    • Result from mutations in genes encoding proteins of the ETC
    • Mutations can be in nuclear or mitochondrial DNA
    • Affect tissues with high energy demand (e.g., nervous tissue, kidney, heart, skeletal muscle)
    • Examples:
      • Parkinson's disease
      • Cardiomyopathies
      • MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
      • Leber hereditary optic neuropathy (LHON)

    Substrate Shuttles

    • Transport electrons from cytosolic NADH to the mitochondrial matrix
    • Examples:
      • Glycerol 3-phosphate shuttle: transfers electrons to mitochondrial FAD
      • Malate-aspartate shuttle: transfers electrons to mitochondrial NAD+

    ATP Production

    • Aerobic ATP production:
      • Glucose is completely oxidized
      • Generates a total of (maximum) 38 ATP molecules per glucose molecule
    • Yield per substrate:
      • NADH+H+: 3 ATP
      • FADH2: 2 ATP
    • Shuttle systems:
      • Glycerol-P shuttle: 36 ATP
      • Malate-aspartate shuttle: 38 ATP

    Coenzymes

    • NAD+: Accepts 2 electrons and 2 protons to become NADH+H+
    • FAD: Accepts 2 electrons and 2 protons to become FADH2
    • Electron energy: These coenzymes carry a lot of energy in the form of electrons.

    Membrane Transport

    • Inner mitochondrial membrane is impermeable to most ions, small, and large molecules:
      • Specific transport systems for specific molecules exist.
      • ADP and Pi are transported in exchange for ATP.

    Revision Exercise

    • Inhibition of any ETC complex leads to inhibition of ATP synthesis and cell death.
    • Toxins affecting ETC: Doxorubicin inhibits CoQ, rotenone inhibits complex I, CN- and CO inhibit complex IV.
    • Oligomycin inhibits ATP synthase by closing the H+ channel.
    • Deficiencies: Fe deficiency inhibits Fe-containing complexes, deficiencies in vitamins B2 or B3 affect the cardiovascular, nervous, muscular, and gastrointestinal systems.

    ATP Production Summary

    • Complete glucose oxidation produces 38 ATP (maximum).
    • 3 ATP per NADH+H+
    • 2 ATP per FADH2
    • Shuttles determine ATP yield:
      • Glycerol-P: 36 ATP
      • Malate-aspartate: 38 ATP

    Uncouplers

    • Exogenous uncouplers:
      • 2,4 dinitrophenol
      • Pentachlorophenol
      • Aspirin (Salicylate) overdose leads to fever
    • Endogenous uncouplers:
      • Bilirubin (at high concentrations)
      • Excess free fatty acids (at high concentrations)
      • Thyroid hormones (T3)
        • By sympathetic stimulation
        • By increasing acylcarnitine production, thereby activating mitochondrial respiration and uncoupling
        • By directly stimulating the transcription of UCP1
    • Uncoupling proteins create a proton leak in the inner mitochondrial membrane, releasing energy as heat.
    • Thermogenin (UCP1) is responsible for heat production in brown adipose tissue.

    Inhibition of the Electron Transport Chain

    • Inhibition of any complex in the electron transport chain inhibits ATP synthesis and leads to cell death.
    • Doxorubicin inhibits at CoQ
    • Rotenone inhibits Complex I
    • CN- and CO inhibit Complex IV by competing with O2 for binding
    • Oligomycin binds to the Fo domain of ATP synthase, closing the H+ channel.

    ETC Deficiency

    • Iron deficiency inhibits any Fe-containing complexes.
    • Deficiency in vitamins B2 or B3 can lead to severe lethargy, complications affecting the cardiovascular, nervous, muscular, and gastrointestinal systems.
    • Niacin (Vitamin B3) is a precursor for NAD, which is a coenzyme for Complex I
    • Riboflavin (Vitamin B2) is a precursor for FAD and FMN, a deficiency inhibits Complex I

    ETC Summary

    • Electron transport chain is the final common pathway for electrons derived from various fuels.
    • NADH and FADH2 are produced in catabolism and the TCA cycle.
    • Reduced coenzymes donate electrons to electron carriers.
    • Electrons move down the chain, losing energy and generating ATP through oxidative phosphorylation (OXPHOS).
    • Energy not converted to ATP is used for transporting Ca2+ and generating heat.

    ATP Production: Aerobic Respiration

    • Glycolysis produces 2 ATP and 2 NADH + H+.
    • Pyruvate to Acetyl CoA produces 2 NADH + H+.
    • TCA cycle produces 6 NADH + H+, 2 FADH2 and 2 ATP.
    • Total theoretical ATP produced: 38 ATP per glucose molecule.
    • 3 ATP molecules per NADH + H+
    • 2 ATP molecules per FADH2
    • Glucose can produce 36 ATP or 38 ATP depending on the specific shuttle system used to transfer electrons.

    Oxidative Phosphorylation

    • Coenzyme Q (ubiquinone) is a mobile carrier within the lipid bilayer.

    Mitochondria: Electron Transport Chain Location

    • ETC is located in the inner mitochondrial membrane.
    • The inner mitochondrial membrane is impermeable to most ions and small or large molecules.
    • Glycolysis takes place in the cytoplasm and produces NADH.
    • NADH and FADH2 need to reach the ETC complex for ATP synthesis.
    • TCA cycle occurs in the mitochondrial matrix (except succinate dehydrogenase which is part of ETC complex II).

    Membrane Transport of Molecules

    • Specific transport systems for other molecules exist within the inner mitochondrial membrane.
    • ADP and Pi are needed for ATP synthesis.
    • ADP is transported in exchange for ATP.

    Substrate Shuttles

    • Substrate shuttles transport specific molecules from the cytosol to the mitochondrial matrix.
    • The inner mitochondrial membrane lacks an NADH transport protein, only electrons from cytosolic NADH are transported.
    • Two main shuttle systems:
      • Glycerol 3-phosphate shuttle: Transfers electrons from NADH to mitochondrial FAD.
      • Malate-aspartate shuttle: Transfers electrons from NADH to mitochondrial NAD+ .

    Royal College of Surgeons in Ireland: Electron Transport Chain (ETC)

    • Module: FFP1, Code: DEM-MED1-101-FFP1
    • Class: MedYear1, semester 1
    • Lecturer: Dr. Jeevan Shetty

    Learning Outcomes

    • Relate oxidative phosphorylation to the overall map of metabolism.
    • Describe the subcellular localization and organization of the components of the ETC and ATP synthase.
    • Discuss the chemiosmotic theory and the coupling of electron transport to ATP generation.
    • Explain how the proton gradient drives ATP synthesis.
    • Explain the normal and pathophysiological outcomes of uncoupling.
    • Describe OxPhos diseases and how iron and vitamin deficiencies can lead to defects in electron transport.

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    Description

    Test your knowledge on exogenous and endogenous uncouplers in cellular respiration and their effects. This quiz covers the mechanisms of uncoupling, examples of inhibitors within the electron transport chain, and the consequences of disruptions in ATP synthesis. Whether you're a student or a biology enthusiast, challenge yourself with questions on mitochondrial function.

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