清華大學(xué)生物化學(xué)課件--脂肪分解代謝(參考版)
2024-08-16 09:33本頁面
【正文】 and when fed with evennumbered, phenylacetate was excreted. ? Hypothesis: the bcarbon is oxidized, with twocarbon units released by each round of oxidation. ? These experiments are a landmark in biochemistry, in using synthetic label (the phenyl group here) to elucidate reaction mechanism, and was done long before radioisotopes was used in biochemistry! Franz Knoop’s labeling experiments (1904): fatty acids are degraded by oxidation at the b carbon, ., b oxidation b b a a 5. Fatty acid oxidation was found to occur in mitochondria ? Enzymes of fatty acid oxidation in animal cells were localized in the mitochondria matrix. ? Revealed by Eugene Kennedy and Albert Lehninger in 1948. 6. Fatty acids are activated on the outer membrane of mitochondria ? Fatty acids are converted to fatty acylCoA (a high energy pound) via a fatty acyladenylate intermediate (enzymebound, mixed anhydride) by the action of fatty acylCoA synthetases (also called fatty acid thiokinase). ? Pyrophosphate is hydrolyzed by inanic pyrophosphatase, thus two anhydride bonds of ATP are consumed to form one highenergy thioester bond, thus pulling the reaction forward: a mon phenomena in biosynthetic reactions. ? Acyladenylates are often formed when –COOH groups are activated in biochemistry. Conversion of a fatty acid to a fatty acylCoA 7. Activated (long chain) fatty acids are carried into the matrix by carnitine ? The fatty acyl group is attached to carnitine (肉堿 ) via transesterification by the action of carnitine acyltransferase I located on the outer membrane of mitochondria, forming fatty acylcarnitine, leaving the CoA in the cytosol. ? The acyl carnitine/carnitine transporter moves acylcarnitine across the inner membrane of mitochondria via facilitated diffusion. ? Mediumchain acylCoAs seem to enter the matrix by themselves, without being carried by carnitine. Fatty acid entry into mitochondria via the acylcarnitine/carnitine transporter ? The acyl group is then transferred back to CoA to form fatty acylCoA by the action of carnitine acyltransferase II located on the inner face of the inner membrane. ? This entering step seems to be ratelimiting for fatty acid oxidation in mitochondria and diseases have been found to be caused by a defect of this step (with aching muscle cramp, especially during fasting, exercise or when on a highfat diet). 8. Fatty acylCoA is oxidized to acetylCoA via multiple rounds of b oxidation The b oxidation consists of four reactions: dehydrogenation hydration dehydrogenation thiolytic cleavage The boxidation pathway ? The 1st dehydrogenation is catalyzed by the membranebound acylCoA dehydrogenase, converting acylCoA to trans?2enoylCoA with electrons collected by FAD and further transferred into the respiratory chain via the electrontransferring flavoprotein (ETF), a
環(huán)評公示相關(guān)推薦
鄂ICP備17016276號-1