Lecture 04

• What is the primary function of the electron transport complexes?

  To oxidise NADH or succinate and reduce oxygen
• What is generated by the electron transport complexes?

  An electrical potential and a proton gradient
• What is the electrochemical potential due to protons called?

  μH+
• What does a higher pH in mitoplasm indicate?

  It indicates a proton gradient is present
• What is the capacity of the electrochemical system to drive ATP synthesis called?

  Phosphorylation potential (Δp)
• What does the equation Δp = ∆𝝍 – ZΔpH represent?

  The relationship of proton motive force to membrane potential
• What does Δp represent in the equation?

  Proton motive force
• What does ∆𝝍 represent in the equation Δp = ∆𝝍 – ZΔpH?

  Membrane potential (voltage difference)
• What is the universal gas constant denoted by?

  R
• What does the term (2.303RT/F) simplify to at 25°C?

  About 59
• What is the approximate value of Δp?

  230 mV
• What is Complex I also known as?

  NADH/Q oxidoreductase or NADH dehydrogenase
• What is the effect of mutations or inhibition of Complex I?

  Associated with Parkinson’s Disease
• What drug inhibits Complex I?

  Metformin
• What is Complex II also known as?

  Succinate dehydrogenase
• What is oxidised in Complex II?

  Succinic acid to Fumaric acid
• How do electrons flow in Complex II?

  From succinate to FMN to iron sulphur centres
• What happens to quinone levels with age?

  They tend to decrease
• What is Complex III also known as?

  Cytochrome C reductase
• What is the function of Complex III?

  Oxidises QH2 back to Q and reduces cytochrome C
• What is the target of azoxystrobin?

  Cytochrome C reductase
• What is the function of Complex IV?

  Re-oxidises cytochrome C and reduces oxygen to water
• What is the reaction catalysed by Complex IV?

  4 cyt C (Fe2+) + O2 + 8H+ => 4 cyt C (Fe3+) + 2H2O + 4H+
• What gases can block the oxygen binding site of Complex IV?

  NO, CO, CN
• How does the ATP to ADP ratio affect electron transport?

  High ATP slows, low ATP increases rate
• What inhibits cytochrome C oxidase?

  Nitric Oxide (NO)
• What is the effect of cis-platin on mitochondrial function?

  Decreases SDH activity of Complex II
• What is the target of Tamoxifen?

  Hormonal receptor
• What is Adriamycin known for?

  Being cardiotoxic and interacting with Complex I
• What do pyridocarbazoles act as?

  Uncouplers that dissipate proton gradient
• What is the main problem with mitochondrial biochemical toxicity?

  It is associated with many drugs and diseases
• What diseases are linked to defects in mitochondrial electron transport?

  Various inherited forms of deafness
• What is one treatment for mitochondrial diseases?

  Genetic screening for mutations
• How do mitochondria contribute to ATP production?

  Produce 70-80% of ATP via oxidative phosphorylation
• What is the link between electron transport and drug toxicity?

  Defects may lead to a wide range of diseases
• What are the main components of the Electron Transport System?

  • Electron transport complexes (I-IV)
  • Proton gradients
  • Membrane potentials
  • ATP synthesis
• What are the effects of drugs on the Electron Transport Complexes?

  • Metformin inhibits Complex I
  • Cis-Platin decreases SDH activity in Complex II
  • Tamoxifen targets hormonal receptors affecting Complexes III and IV
  • Adriamycin interacts with Complex I and is cardiotoxic
  • Pyridocarbazoles act as uncouplers and inhibit Complex IV
• What diseases are associated with defects in mitochondrial electron transport?

  • Parkinson's Disease (Complex I)
  • Alzheimer's Disease (Complex IV)
  • Heart Disease (Complex III)
  • Various inherited forms of deafness
  • Myopathy and lactic acidosis (Nucleotide Transporter)