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This case study explores the oxidative reactions in the electron transport chain and their role in ATP synthesis. It also discusses the role of the electron transport chain in various diseases.
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BC368 Biochemistry of the Cell II Electron Transport Chain CH 19 (pp 731-747) March 19, 2015 http://www.science-groove.org/Now/Oxidative.html
Case Study • Last fall, Michael Phelps was pulled over in Baltimore after police spotted him driving erratically. • A Breathalyzer test revealed that Phelps’ blood alcohol content was 0.14, well over the 0.08 legal limit.
Redox Reactions 2 Cr2O72-+ 3 C2H5OH + 16 H+--> 4 Cr3++ 3 CH3CO + 11 H2O • Ethanol is oxidized; dichromate is reduced. • Reaction can be monitored through a color change of the chromium species.
Half Reactions Cr2O72-+ 14 H+ + 6 e- -->2 Cr3++ 7 H2O C2H5OH + H2O --> CH3COOH + 4 e- + 4 H+ Reduction (cathode) Oxidation (anode) Overall: 2 Cr2O72-+ 3 C2H5OH + 16 H+--> 4 Cr3++ 3 CH3COOH + 11 H2O
Half Reactions Higher tendency for reduction • Standard reduction potentials are for reduction. • In general, ’cell = ’cathode - ’anode Reduced Oxidized Lower tendency for reduction
Half Reactions Cr2O72-+ 14 H+ + 6 e- -->2 Cr3++ 7 H2O C2H5OH --> CH3COOH + 2 e- + 2 H+ Reduction (cathode); = 1.33 V Oxidation (anode); = 0.058 V (for the reduction) cell = 1.33 V - 0.058 V = 1.27 V
Half Reactions • In general, ’cell = ’cathode - ’anode Reduced Oxidized ’cell > 0 is favorable DG’ = -nF’cell
In-Class Problem • ATP is made through oxidative phosphorylation, powered by the free energy released from electron transfer from NADH to O2. • a) Given the following reduction potentials, calculate the available standard free energy from this process. • NAD+ + H+ + 2 e- NADH E’º = -0.32 V • 1/2 O2 + 2 H+ + 2 e- H2O E’º = 0.82 V • b) If three ATP’s are synthesized per electron pair transferred, what is the efficiency of the process?
Chemiosmotic Mechanism • Electron transport chain sets up an H+ gradient (proton motive force). • Energy of the pmf is harnessed to make ATP.
Fig 19-2 Mitochondrion • Double membrane, with inner membrane very impermeable • TCA occurs in the matrix • ETC in the inner membrane
Case Study The patient was delivered by emergency C-section at 31 weeks of gestation. He required intubation in the delivery room because of apnea and bradycardia and was treated in the Neonatal Intensive Care Unit. A follow-up chest X-ray taken at 1 month of age showed an enlarged heart and prompted a cardiology consult. Although there was no clinical evidence of congestive heart failure, the cardiac ultrasound showed a significant decrease in left ventricular function. The family history was significant in that the patient’s maternal uncle died from sudden infant death syndrome. At 11 months of age, the patient’s mother was concerned about his poor weight gain and development because he was not yet sitting alone.
Case Study At his 20th-month visit, persistent muscle weakness, growth delays, and congestive cardiomyopathy led the cardiologist to make a genetics referral. Two days following this clinic visit, however, the patient presented to his primary care provider with cough, wheezing, runny nose, and one day of fever and mental status change. His condition deteriorated, requiring intubation, and he was transferred to the Pediatric Intensive Care Unit. The diagnosis was pneumonia, and severe lactic acidosis was found. He failed to respond to aggressive treatment and died from repeated ventricular fibrillation that occurred 10 days later. Autopsy limited to the heart was performed. The gross and microscopic findings were characteristic of Barth syndrome. The heart weighed 100 g (average for his age is 56 g, and 100 g is the average for a 7-year-old).
Cardiolipin • A small number of boys suffer from Barth syndrome (~50 births/year in the United States). • Barth’s results from a mutation on the X chromosome in the gene coding for taffazin, an enzyme involved in the biosynthesis of cardiolipin. • Patients with Barth syndrome have abnormal mitochondria and cannot maintain normal rates of ATP production. These patients develop life- threatening cardiomyopathy and muscle weakness.
ETC carriers: Coenzyme Q • Mobile electron carrier within the bilayer • 1- or 2-electron acceptor Fig 19-3
ETC carriers: FMN • Prosthetic group of ETC protein (complex I) • 1- or 2-electron acceptor
ETC carriers: Cytochromes • Heme proteins • Most are integral proteins • Cytochrome c is a soluble peripheral protein
ETC carriers: Iron-sulfur proteins Fig 19-5
ETC carriers: Copper centers • CuA center • CuB center
Electron Transport Chain ~Fig 19-16
Alternate Entries Fig 19-8
Alternate Entries • Complex II (aka succinate dehydrogenase)
Alternate Entries Fig 19-8
Alternate Entries Fig 19-8
Complex III Fig 19-11
Complex IV Fig 19-14
Electron Transport Chain Succinate dehydrogenase • Electrons flow from carriers with low to high reduction potential. • This is energetically downhill.
Per electron pair: Electron Transport Chain 4 H+in 4 H+out Succinate dehydrogenase 4 H+out 4 H+in • Some carriers pump protons. 2 H+in 2 H+out
Inhibitors of electron transport Fig 19-6
Case Study Four carriers (a, b, c, d) are required for respiration in a novel bacterial electron-transport system. In the presence of substrate and O2, three different inhibitors block respiration as shown. What is the order of carriers? Inhibitor a b c d 1 + + - + 2 - - - + 3 + - - + “+” = fully oxidized; “-” = fully reduced
O2 consumption as a measure of electron transport • An oxygen electrode can measure O2 consumption in respiring mitochondria.
O2 consumption as a measure of electron transport Substrate added Substrate consumed • An oxygen electrode can measure O2 consumption in respiring mitochondria.
O2 consumption as a measure of electron transport • An oxygen electrode can measure O2 consumption in respiring mitochondria.
Coupling of electron transport and ATP synthesis • Data can be reported as O2 concentration or O2 consumption.
