33 - Friday, November 12, 2010 Lecture 33 Announcements: 1....

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Friday, November 12, 2010 Lecture 33 Announcements: 1. Quiz 8 results: A 19.7 B 20.2 C 20.4 2. Meet today, 2:55PM in Comstock B108: Interviewing for HCEC and medical school evaluation-- what are they looking for? 3. Do the next PyMol assignment (for quiz 9 on 11/17): ATP Synthase. Be warned-- the lecture will not get to ATP Synthase until Mon 11/15. 4. Pick up regraded exams! After today's lecture, all regraded exams will be brought over to the Reserve Desk at the Bio Center in 216 Stimson. 5. HCEC orientation Wed 11/17 at 5:00PM in room 203 Phillips Hall (this session repeats the overflow session of 11/3). Wednesday's lecture: Urea Cycle Oxidative Phosphorylation: brief history the electron transport chain Today's lecture p. 227 Here is Peter Mitchell’s reasoning: Notice the following favorable rxn: NADH + H + + 1/2 O 2 NAD + + H 2 O , E o ' = 1.14 V G o ' = -nF E o ' = -220 kJ/mol How is this redox reaction (or redox of FADH 2 ) coupled to the following reaction? ADP + Pi + H + ATP + H 2 0 G o ' = +31 kJ/mol Mitchell’s answer: The oxidation of NADH (or FADH 2 ) drives the formation of a proton gradient , where the [H + ] cytosol is higher than the [H + ] matrix , and the mitochondrial matrix has a negative electrical potential compared to the cytosol. Once this gradient of [H + ] and electrical potential is formed, H + can then undergo the following very favorable reaction: G transport = RTln([H+] matrix /[H+] cytosol ) + nF E o ' This rxn, H + flowing from cytoplasm into mitochondrial matrix, will be favorable based upon [H+] cytosol > [H+] matrix and a value of E o ' that is negative inside the matrix.
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p. 228 This diagram provides the simple overview of oxidative phosphorylation. Note (1) that H+ get pumped out of the matrix, the [H+] is higher in the cytosol; (2) also, because H+ are pumped into the cytosol, there voltage gradient across the inner mito membrane is + in the cytosol (- in the matrix); and (3) there are four separate complexes within the inner mito membrane. p. 229 Continuing this overview: First, note that two different reduced molecules, NADH and FADH2, are starting materials for oxidative phosphorylation. (1) For efficiency, the very favorable oxidation of NADH or FADH2 occurs in small steps; each small step happens at one of the 4 complexes; this process gradually builds up a gradient of H+ concentration and voltage across the inner mitochondrial membrane. (2) At each step except the last one, some of the free energy is retained as a reduced molecule, starting from the excellent reducing agent NADH, the slightly less powerful reducing agent FADH2, then the “pretty good” reducing agent UQH2, and finally in the weaker reducing agent cytochrome c. This last reduced molecule is ready at the last step to react with oxygen. This last step drives the overall reaction. (3) Free energy storage builds up as the gradient of H+ and
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33 - Friday, November 12, 2010 Lecture 33 Announcements: 1....

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