Fill in the Blank The provision of acetyl-CoA by fatty acid ?-oxidation is the m

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The provision of acetyl-CoA by fatty acid ?-oxidation is the main factor determining the rate of ketone body synthesis. Fatty acids are activated by ---------------------- present in the mitochondrial outer membrane. Activated fatty acids are then transported into the mitochondria via the mitochondrial carnitine transport system and are sequentially chain-shortened, yielding acetyl-CoA and reducing equivalents.

Under normal dietary conditions, hepatic production of ketone bodies, acetoacetate, and D-3-hydroxybutyrate is minimal and the concentrations of these compounds in blood is low. However, during food deprivation the synthesis of ketone bodies is greatly enhanced, and the circulating concentration of ketone bodies can reach values of approximately 5 mM. The first committed step of hepatic ketone body synthesis is the condensation of two acetyl-CoA molecules to yield acetoacetyl-CoA. The second step in the pathway is the formation of 3-hydroxy-3-methylgluratyl-CoA catalyzed by the enzyme 3-hydroxy-3-methylgluratyl-CoA synthase (HMG-CoA synthase). In liver there are two HMGCoA isoforms, one in the cytosol and one in the mitochondria. The former takes part in -------------------------, whereas the mitochondrial form catalyzes the formation of HMG-CoA for ketone body formation.

Explanation / Answer

The provision of acetyl-CoA by fatty acid beta-oxidation is the main factor determining the rate of ketone body synthesis. Fatty acids are activated by carnitine palmitoyltransferase present in the mitochondrial outer membrane. Activated fatty acids are then transported into the mitochondria via the mitochondrial carnitine transport system and are sequentially chain-shortened, yielding acetyl-CoA and reducing equivalents.

Under normal dietary conditions, hepatic production of ketone bodies, acetoacetate, and D-3-hydroxybutyrate is minimal and the concentrations of these compounds in blood is low. However, during food deprivation the synthesis of ketone bodies is greatly enhanced, and the circulating concentration of ketone bodies can reach values of approximately 5 mM. The first committed step of hepatic ketone body synthesis is the condensation of two acetyl-CoA molecules to yield acetoacetyl-CoA. The second step in the pathway is the formation of 3-hydroxy-3-methylgluratyl-CoA catalyzed by the enzyme 3-hydroxy-3-methylgluratyl-CoA synthase (HMG-CoA synthase). In liver there are two HMGCoA isoforms, one in the cytosol and one in the mitochondria. The former takes part in mevalonic acid for cholesterol synthesis, whereas the mitochondrial form catalyzes the formation of HMG-CoA for ketone body formation

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