Ketogenesis酮体代谢.pptVIP

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 During high rates of fatty acid oxidation, primarily in the liver, large amounts of acetyl-CoA are generated. These exceed the capacity of the TCA cycle, and one result is the synthesis of ketone bodies, or ketogenesis. The ketone bodies are acetoacetate, b-hydroxybutyrate, and acetone. Ketone bodies b-hydroxybutyrate Acetoacetate acetone b-Hydroxybutyrate and acetoacetate are fuel molecules They have less potential metabolic energy than the fatty acids from which they are derived but they make up for this deficiency by serving as “water-soluble lipids” that can be more readily transported in the blood plasma. During starvation, ketone bodies are produced in large amounts becoming substitutes for glucose as the principal fuel for brain cells. Ketone bodies are also metabolized in skeletal muscle and in the intestine during starvation. Ketone Bodies Are Synthesized in the Liver In mammals, ketone bodies are synthesized in the liver and exported for use by other tissues. Ketone body synthesis : First, two molecules of acetyl CoA condense to form acetoacetyl CoA and HS–CoA in a reaction catalyzed by acetoacetyl-CoA thiolase. Subsequently, a third molecule of acetyl CoA is added to acetoacetyl CoA to form 3-hydroxy-3-methylglutaryl CoA (HMG CoA) in a reaction catalyzed by HMG-CoA synthase. These steps are identical to the first two steps in the isopentenyl diphosphate biosynthesis pathway . Acetoacetate and 3-hydroxybutyrate are interconverted by the mitochondrial enzyme D(-)-3-hydroxybutyrate dehydrogenase; the equilib