ketogenesis课件.ppt

Ketogenesis酮体代谢;Increased fatty acid oxidation is a characteristic of starvation and of diabetes mellitus, leading to ketone body production by the liver (ketosis). Ketone bodies are acidic and when produced in excess over long periods, as in diabetes, cause ketoacidosis (酮酸中毒), which is ultimately fatal. Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to hypoglycemia(低血糖). ;Definition;Ketone bodies: b-hydroxybutyrate Acetoacetate acetone;Interrelationships of the ketone bodies. D(?)-3-hydroxybutyrate dehydrogenase is a mitochondrial enzyme.;Ketone Bodies Are Synthesized in the Liver;Acetoacetate and 3-hydroxybutyrate are interconverted by the mitochondrial enzyme D(-)-3-hydroxybutyrate dehydrogenase; the equilibrium is controlled by the mitochondrial [NAD+]/[NADH] ratio, ie, the redox (氧化还原作用) state. Enzymes responsible for ketone body formation are associated mainly with the mitochondria.;Formation, utilization, and excretion of ketone bodies. ;Two acetyl-CoA molecules formed in β-oxidation condense with one another to form acetoacetyl-CoA by a reversal of the thiolase reaction. Acetoacetyl-CoA, which is the starting material for ketogenesis, also arises directly from the terminal four carbons of a fatty acid during β-oxidation. ;Condensation of acetoacetyl-CoA with another molecule of acetyl-CoA by 3-hydroxy-3-methylglutaryl-CoA synthase forms HMG-CoA. 3-Hydroxy-3-methylglutaryl-CoA lyase then causes acetyl-CoA to split off from the HMGCoA, leaving free acetoacetate. ;Pathways of ketogenesis in the liver;Ketone Bodies Are Oxidized in Mitochondria;Conversion of acetoacetate to acetyl CoA.;Ketone bodies are broken down only in nonhepatic tissues because this transferase is present in all tissues except live. In most cases, ketonemia is due to increased production of ketone bodies by the liver rather than to a deficiency in their utilization by extrahepatic tissues;Ketone Bodies Serve as a Fuelfor Ext