Ketogenesis Flashcards
During fasting, oxaloacetate gets used up for
gluconeogenesis and the liver converts excess acetyl-CoA from β-oxidation of fatty acids to ketone bodies.
Ketone bodies include
acetoacetate, β-hydroxybutyrate and acetone. They are excreted as acetone.
Cardiac muscles, skeletal muscles and renal cortex metabolize ketone bodies to
acetyl-CoA
During a fast, this metabolism prevents accumulation of
ketone bodies in the blood, after about a week, the brain begins to metabolize them too.
Ketone bodies accumulation in the blood can result in
ketoacidosis.
Occurs in the mitochondria of hepatocytes when excess acetyl-CoA accumulates in the fasting state.
KETOGENESIS
forms HMG-CoA from acetyl-CoA, HMG-CoA lyase forms acetoacetate from HMG-CoA and acetoacetate is reduced to β-hydroxybutyrate.
HMG-CoA synthase
is a non-enzymatic side-product of acetoacetate. It is not used as fuel but imparts a fruity odor used in diagnosing ketoacidosis
Acetone
Acetoacetate synthesized in the liver and delivered to the blood is activated by
succinyl-CoA acetoacetate-CoA transferase (thiophorase).
succinyl-CoA acetoacetate-CoA transferase (thiophorase) is present in extrahepatic tissue but not in the liver
therefore the liver does not use ketones for fuel
b-ketothiolase catalyzes the formation of
2 Acetyl CoA from acetoacetylCoA and CoA-SH
The brain uses glucose from glycogenolysis for about 12hrs then glucose from gluconeogenesis for about 1 week thereafter
ketones become its source of energy.
Excessive accumulation of ketone bodies in the blood with a shift towards the formation of β-hydroxyacetate.
There are home kits that measure blood β-hydroxybutyrate.
It is a common complication of uncontrolled DM and chronic alcoholism.
It is associated with polyuria, thirst and dehydration, hypokalemia, decreased HCO3- and acetone breath.
KETOACIDOSIS
