Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Slide 39Slide 40Slide 41Slide 42Slide 43Slide 44Slide 45Slide 46Slide 47Metabolic BiochemistryLecture 8 Aug. 17, 2005Oxidative PhosphorylationOther Pathways of Carbohydrate MetabolismLNC Fig.19.15Succinate + FAD fumarate + FADH2FADFMNH+H+H+Proton pumping and Storage of Free Energy++++++------MatrixIMSinner membraneLNC 19-6G = 2.3 RT pH + 1 x F x pH = ~ 0.75~ 0.15 - 0.2 v = 200 mVG = ~ +20 kJ/mol (H+)The oxidation of NADH liberates ~ 220 kJ/mol (NADH)therefore,we can pump ~ 11 protons at 100% efficiencytightly coupled vsuncoupled mitochondriasuccinateLNC 19-18aEffect of antibiotics valinomycin and nigericinValinomycin is a K+ ionophoreit breaks down the membrane potentialNigericin is a H + /K + antiporterit exchanges protons for potassium ions and thus converts a proton gradient into a K + gradientATP SynthaseComplex VFoF1 ATP SYNTHASEF1: Fo: a b2 c9-12QuickTime™ and aGIF decompressorare needed to see this picture.QuickTime™ and a decompressorare needed to see this picture.QuickTime™ and a decompressorare needed to see this picture.QuickTime™ and a decompressorare needed to see this picture.QuickTime™ and a decompressorare needed to see this picture.The engine can turn in both directions:with ATP hydrolysis it turns in the opposite directionwhen compared with ATP synthesis driven by proton flux into the matrixInteresting questions:How many protons enter per ATP produced (per 120o turn)?How many c-subunits per subunit?A simple estimate10 PROTONS pumped per NAD+ oxidized10 PROTONS pumped per OXYGEN consumed3 PROTONS pass through the ATP synthase per 120o turn 1 ATP is made per 120o turnTherefore: 3ATP per 360o turn3 ATP / 9 PROTONS3 ATP per OXYGEN (or per NADH oxidized):P/O ratio = 3Experimental measurements of P/O ratios:P/O = ~ 2.5Is that a problem?NO! There are other ways for protons to go back to the matrixwithout passing through the ATPsynthase:COUPLING is not perfectThermoregulationThermogenesis(limited amount)In the presence of an uncoupler the P/O ratio is reduced to zeroLNC 19-17bOligomycin is a highly specific inhibitor of the ATP synthaseUncoupling protein, UCPLNC 19-28We have > 6 genes for differentisozymes of uncoupling proteins”:UCP-1, UCP-2, UCP-3, …..they are differentially expressedIn different tissues and cellsMills, et al., NATURE|VOL 426 | 27 NOVEMBER 2003|The recreational use of amphetamine type stimulants can produce a marked and sometimes lethal increase in body temperature. Here we show that mice deficient in a mitochondrial protein known as UCP-3 (for ‘uncoupling protein-3’) have a diminished thermogenic response to the drug MDMA (3,4 methylenedioxymethamphetamine, nicknamed ‘ecstasy’) and so are protected against this dangerously toxic effect. Our findings indicate that UCP-3 is important in MDMA-induced hyperthermia and point to a new therapeutic direction for solving an increasing public health problem.QH2 can also be oxidized directly through a cyanide-insensitive oxidaseLNC box 19-1Alternative NADH oxidases exist in plant mitochondriaNo proton pumping and hence no ATP synthesis The free energy from the oxidation of NADH appears as HEATEastern skunk cabbageAmorphophallus konjacVoodoo LillySeymour et al. NATURE 426, 243-244 (2003)…..heat produced by the flower constitutes an important energy reward to pollinators, allowing them to feed and mate at a fraction of the energy cost that would be required outside the flower.•End of lecture 8•August 17,
View Full Document
Unlocking...