Ketone Bodies, Ketogenesis, Ketolysis Flashcards
What is the main energy reserve in the body?
TAG
What are the end products of lipolysis?
glycerol and Acetyl-CoA
What is the post-prandial state?
The period after eating. Lasts until last meal is digested. Glucose coming from glycogenolysis
How goes TAG breakdown occur during the fasting state?
During fasting, the glucagon/insulin ratio rises, causing cAMP levels to be elevated. Protein kinase A is activated and phosphorylates hormone-sensitive lipase (HSL), activating this enzyme. HSL-P initiates the mobilization of adipose triacylglycerol by removing a fatty acid. Other lipases then act, producing fatty acids and glycerol. Insulin stimulates the phosphatase that inactivates HSL in the fed state
Where are ketone bodies synthesized?
In the liver
NOTE: they are NOT used there
What is the principle fate of ketone bodies?
conversion back to acetyl CoA and oxidation in the TCA cycle in other tissues.
What is the first step of ketogenesis?
Enzymes?
Bi-products?
conversion of 2 acetyl-CoA to acetoacetyl-CoA
enzyme: thiolase
bi-products: CoA-SH
What is the 2nd step of ketogenesis?
Enzymes?
Bi-products?
conversion of acetoacetyl-CoA to HMG-CoA (using acetyl CoA)
enzyme: HMG-CoA synthase
bi-products: CoA-SH
What is the 3rd step of ketogenesis?
Enzymes?
Bi-products?
conversion of HMG-CoA to acetoacetate
bi-products: Acetyl-CoA
enzyme: HMG-CoA lysase
What is the final step of ketogenesis?
Enzymes?
Bi-products?
two things: either,
1) spontaneous, non-enzymatic decarboxylation of acetoacetate to acetone (giving off Co2) or,
2) conversion to D-B-hydroxybutyrate (using NADH+ H+ and making NAD+)
enzyme: D-B-hydroxybutyrate dehydrogenase
What happens to acetone?
Acetone is excreted via the lungs. Can be detected by its odor (ketone breath).
Probably not metabolized.
Why can’t the liver perform ketolysis?
the liver does not contain the enzymes needed to oxidize acetoacetate to acetoacetyl-CoA
NOTE: the steps of ketolysis are the same as ketogenesis in reverse, except for the enzyme used to oxidize acetoacetate to acetoacetyl-CoA
What enzyme is used to oxidize acetoacetate to acetoacetyl-CoA during ketolysis?
any bi-products?
succinyl CoA acetoacetate CoA transferase
uses succinyl coA and makes succinate
Does plasma concentration of fatty acids or glucose vary much in the starving state?
No, they are fairly constant. Ketone bodies increase drastically during fasting states (especially B-hydroxybutyrate)
How is ketogenesis regulated?
(1) The supply of fatty acids is increased.
(2) The malonyl CoA inhibition of CPTI is lifted by inactivation of acetyl CoA carboxylase.
(3) β-Oxidation supplies NADH and FAD(2H), which are used by the electron transport chain for oxidative phosphorylation. As ATP levels increase, less NADH is oxidized, and the NADH/NAD+ ratio is increased.
(4) Oxaloacetate is converted into malate because of the high NADH levels, and the malate enters the cytoplasm for gluconeogenesis
(5) Acetyl CoA is diverted from the TCA cycle into ketogenesis, in part because of low oxaloacetate levels, which reduces the rate of the citrate synthase reaction.
