Download Acetyl CoA

METABOLISM OF
ketone bodies
Starved state
Glycerol-P
Glycerol
Glucose
Triacylglycerol
Fatty acyl CoA
gluconeogenesis
Pyruvate
Acetyl CoA
TCA cycle
Malonyl CoA
Ketone bodies
Fatty acid
Starved state
Glycerol-P
Glycerol
Glucose
gluconeogenesis
Triacylglycerol
Fatty acyl CoA
Carnitine
transporter
Pyruvate
Acetyl CoA
TCA cycle
Malonyl CoA
Ketone bodies
Glucagon/
epinephrine
Fatty acid
Ketone bodies
•
The acetyl-CoA formed in
the liver during b-oxidation
can have two fates:
1. Enter the TCA cycle
2. Converted to “ketone bodies”
– acetone, acetoacetone and
b-hydroxybutyrate – for
export to other tissues
Ketone bodies formed in the liver
1. Condensation of two
molecules of acetylCoA,
2. The resulting
acetoacetyl-CoA
condenses with acetylCoA to form bhydroxy-bmethylglutaryl-CoA
(HMG-CoA)
3. Cleavage of HMG-CoA
yields acetyl-CoA and
acetoacetate.
4. Reduction of acetoacetate
yields D-bhydroxybutyrate (do not
confuse with L- bhydroxybutyrate of the boxidation pathway).
5. Acetoacetate is easily
decarboxylated (may be
spontaneously or
enzymatically) to acetone
and CO2.
Ketone bodies are exported to
other organs
• Acetone, produced in smaller quantities
than the other ketone bodies, is exhaled
• Acetoacetate and b-hydroxybutyrate are
transported in the blood to tissues other than
the liver
Ketone bodies as fuels
 b-hydroxybutyrate may
be converted to acetylCoA.
 The acetyl-CoA is
Oxidized in the TCA
cycle to provide much of
the energy required by
tissues
Ketone bodies are used under
starvation conditions
• The brain, which preferentially uses glucose
as fuel, can adapt to the use of acetoacetate
or b-hydroxybutyrate under starvation
conditions, when glucose is unavailable
Intertissue relationships during starvation