清華大學生物化學課件--脂肪分解代謝-資料下載頁

　　

【正文】 tions, oxaloacetate concentration in hepatocyte will be low: the rate of glycolysis is low (thus the supply of precursors for replenishing oxaloacetate is cut off) and oxaloacetate is siphoned off into gluconeogenesis (to maintain blood glucose level). ? The acetylCoA generated from active fatty acid oxidation can not be oxidized via the citric acid cycle and will be converted to acetoacetate, bhydroxylbutyrate, and acetone (., the ketone bodies, 酮體 ) in mitochondria for export to other tissues. Ketone body formation and export from the liver Formation of ketone bodies from acetylCoA 14. Ketone bodies are converted back to acetylCoA in extrahepatic tissues ? Dbhydroxylbutyrate is reoxidized to acetoacetate (catalyzed by the dehydrogenase). ? Acetoacetate is then converted to acetoacetylCoA using succinylCoA (catalyzed by bketoacylCoA transferase). ? AcetoacetylCoA is cleaved to two acetylCoA (again catalyzed by thiolase). ? Heart, skeletal muscle and the renal cortex use acetoacetate in preference to glucose. ? The brain adapts to the utilization of acetoacetate during starvation and diabetes. bHydroxybutyrate can be used as a fuel by extrahepatic tissues Not present in liver Overproduction of ketone bodies in uncontrolled diabetes or severely reduced calorie intake can lead to acidosis and ketosis. Keywords ? Activation and transport of fatty acids ? boxidation reaction and regulation ? Ketone bodies Words of the week ? ketosis ? acidosis ? ketoacidosis ? alkalosis Summary ? Diet triacylglycerols are emulsified by bile salts in the intestines before being absorbed and transported in blood as chylomicron particles. ? Stored triacylglycerols are mobilized in response to hormones and fatty acids in blood are carried by serum albumin. ? Fatty acids are activated to the acylCoA form and is then carried into mitochondria by carnitine with the help of two carnitine acyltranseferase isozymes (I and II) located on the outside and inside of the inner membrane. ? AcylCoA is converted to acetylCoA after going through multiple rounds of the fourstep (dehydrogenation, hydration, dehydrogenation and thiolysis) boxidation pathway. ? Oxidative degradation of unsaturated fatty acids need two extra enzymes: an isomerase and a reductase. ? The propionylCoA generated from oddnumbered fatty acids is converted to succinylCoA after being carboxylated, epimerized and intramolecularly rearranged (with help from a coenzyme B12). ? The rate of boxidation pathway is controlled by the rate at which acylCoA is transported into mitochondria. ? The boxidation pathway also occurs in peroxisomes using similar isozymes, but generates H2O2. ? Excess acetylCoA (under conditions when glucose metabolism is not optimal) can be converted to ketone bodies in the liver cells and reconverted into acetylCoA in extrahepatic cells.