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Oxidative Phosphorylation Part 3: Regulation
Regulation by inhibition and energy barriers
Undergraduate 3

Additional Biochemistry Flashcards




Oxidative Phosphorylation is Regulated bu Cellular Energy Needs
  • Rate of O2 consumption in mitochondria is limited by the availability of ADP as a substrate for phosphorylation
  • this dependence on ADP as a Pi acceptor is called acceptor control of respiration
  • acceptor control ratio is the ratio of max rate ADP induced O2 consumption to the basal rate in the absence of ADP
  • mass-action ratio  of the ATP-ADP system[ATP]/([Pi][ADP])
  • normally ratio is high
  • when rte of energy requiring processes increases, rate of ATP break down increases, lowering MAR
  • now more ADP is available and rate of oxidative phosphorylation increases---regenerating ATP
  • then MAR is returned to high levels and respiration slows again
Inhibitory Protein Prevents ATP Hydrolysis During Hypoxia
  • when cell is hypoxic, electron transfer to oxygen slows and so does pumping of protons
  • proton motive force collapses and ATP synthase could operate in reverse, hydrolyzing ATP to pump protons outward
  • this is prevented by IF1 protein, which binds ATP synthase molecules and inhibits ATPase activity
  • only active at pH 6.5
  • if low oxygen, then cell glycolysis makes ATP and makes cell more acidic (lactic acid)
Hypoxia Leads to ROS production and several Adaptive Responses (prolly don't really need for test)
  • in hypoxic cells there is an imbalance between the input of electrons from fuel oxidation in the matrix and transfer of electrons to O2, leading to formation of reactive oxygen species-ROS
  • one way to guard against ROS is regulating pyruvate dehydrogenase (delivers acetyl-CoA to the citric acid cycle). Low O2 conditions cause PDH kinase to phosphorylate mitochondrial PDH, inactivating it and slowing delivery of FADH2 and NADH from the citric acid cycle  to the respiratory chain
  • an other way to prevent ROS is by replacing one subunit of complex IV, which is better suited in low O2 conditions
  • both defense mechanisms are mediated by HIF-1(hypoxia inducible factor)
  • a transcription factor which accumulates in hypoxic cells and triggers synthesis of PDH kinase, COX4-2 and protease for COX4-1
  • (figure 19-32)
ATP Producing Pathways are Coordinately Regulated
  • Relative concentrations of ATP and ADP control the rates of electron transfer, oxidative phosphorylation, citric acid cycle , pyruvate oxidation, and glycolysis
    • Whenever ATP consumption increases, the rate of electron transport and oxidative  phosphorylation increases as well
    • simultaneously the rate of pyruvate  oxidation to acetyl-CoA via the citric acid cycle increases, increasing the flow into the respiratory chain
    • these can in turn increase glycolysis, increasing the rate of pyruvate formation
    • When conversion of ADP to ATP lowers the ADP [], acceptor control slows electron transfer and thus oxidative phosphorylation
    • glycolysis and citric acid cycle are also slowed because ATP is allosteric inhibitor of PFK-1 and PDH
    • . when citrate accumulates in mitochondria it is xported to cytosol where it binds allosterically along with ATP to PFK-1
  • [image]
Mitochondria in Thermogenesis, Steroid Synthesis and Apoptosis
  • newborn mammals contain brown adipose tissue
  • in these tissues oxidative phosphoylation us used to keep the animal warm
  • tissue contains a large amount of mitochondria
  • these have an uncoupling protein in their inner membrane called thermogenin
  • provides a path for protons to return to the matrix without passing through the F1Fo complex
  • energy of oxidation is not conserved by ATP formation---released as heat
  • [image]
Mitochondrial P-450 oxygenases catalyze Steroid Hydroxlyations
  • Site of biosynthetic reactions that produce steroid hormones and sex hormones
  • synthesized from cholesterol or the cytochrome P-450 family enzymes
  • in hydroxylation, on atom of oxygen is incorporated into the substrate and the other is reduced to H2O
  • electron flow in P-450..
  • [image]
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