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4 Cards in this Set
- Front
- Back
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What are the fates of acetyl CoA in liver from fatty acid oxidation? What are the ketone bodies and their fates in the body? Why would we make ketone bodies? What organs use ketone bodies the most? What source provides ketone bodies? |
They can undergo the citric acid cycle or conversion to ketone bodies. They include acetone (exhaled by mouth)and acetoacetate and Beta-hydroxybutyrate (which are both exported to other tissues to made into acetyl-CoA to go through TCA cycle). TCA cycle requires both oxaloacetate and acetyl-CoA to make citrate. But when OAA is all used up, ketone bodies are necessary to make for other organs to use as fuel. It also frees up CoA for continued beta-oxidation. Under starvation, they include the brain, skeletal muscles, the heart, and the renal cortex. It is the liver that provides ketone bodies. |
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What is the steps of ketone body formation? |
It is the formation of acetoacetate, occurring in the liver through condensation of two molecules of acetyl-CoA, catalyzed by thiolase (last step of beta-oxidation pathway). It is then condensed with acetyl-CoA to form Beta-hydroxy-Beta-methylglutaryl-CoA, which is then cleaved to free acetoacetate and acetyl-CoA. Acetoacetate is then reversibly reduced by Beta-hydroxy-butyrate dehydrogenase to Beta-hydroxybutyrate. Acetoacetate can also be made into acetone by acetoacetate decarboxylase. |
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Ketone body as fuel: How are they oxidized to make fuel? Can the liver use ketone bodies for fuel? |
Once they reach extra hepatic tissues, Beta-hydroxybutyrate is oxidized to acetoacetate by beta-hydroxybutyrate DH. Acetoacetate is activated by transfer of CoA from succinyl-CoA (TCA cycle intermediate) catalyzed by Beta-ketoacyl-CoA transferase. Acetoacetyl-CoA is cleaved by thiolase to make two acetyl-CoA’s, which enter the citric cycle and become fuel. Because the liver lacks the enzyme, ketone bodies are not used as fuel in the liver. They are released instead into the blood. |
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Starvation: What occurs during this process? What hormone is secreted? What is acidosis? What is ketosis? |
During starvation, all carbohydrate stores are used up (blood glucose and glycogen). Glucagon is secreted where gluconeogenesis depletes citric acid cycle intermediates, including OAA, which will divert acetyl-CoA conversion to ketone body production. Fats are mobilized by glucagon, so it is in the bloodstream for liver and muscle. [Malonyl-CoA] decreases, so fatty acids enter liver mitochondria to be degraded to acetyl-CoA. Acetyl-coA builds up and can’t be used for TCA cycle, so it is converted to ketone bodies. Increased blood levels of ketone bodies lower the pH of blood, resulting in acidosis, which can lead to coma and death. Ketone bodies in blood and urine of untreated diabetes can reach high levels in a condition called ketosis. |
