清華大學生物化學課件--脂肪分解代謝-文庫吧
2025-07-21 09:33 本頁面
【正文】 pathway 4. Early labeling experiments (1904): fatty acids are degraded by sequential removal of twocarbon units ? When dogs were fed with oddnumbered fatty acids attached to a phenyl group, benzoate was excreted。 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 th
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