Beta Oxidation of Fatty Acids and Ketone Body

Beta oxidation of
fatty acids and

ketone body
metabolism
By:Gesese
β-oxidation
• The principal pathway for catabolism of fatty acids.
• Takes place in mitochondrial matrix of tissues in

animals.
The complete oxidation of fatty acids to CO2
and H2O takes place in 3 stages:
1. The oxidation of long-chain fatty acids to two-

carbon
fragments, in the form of acetyl-CoA, through β-

oxidation.
2. The oxidation of acetyl-CoA to CO2 in the citric acid

cycle,
3. The transfer of electrons from reduced electron

-Oxidation of Saturated
FAs
There are four basic steps:
Step I: Unsaturation (dehydrogenation)
Catalyzed by acyl-CoA dehydrogenase & FAD.
Step II: Hydration
Catalyzed by enoyl-CoA Hydratase which helps
the
addition of H2O  to saturate double bond.

Step III: Oxidation
Dehydrogenation by -Hydroxy acyl CoA

dehydrogenase & NAD+.
Step IV : Splitting of active acetate-
- By Thiolase (acyl-CoA acetyl transferase)

- It splits acyl CoA into Acetyl CoA & Acyl CoA,
which is
shorter than the first one by 2 carbon atoms.

The process is repeated until the whole FA is
Broken into acetyl CoA; w/c are then oxidized to
CO & H O in Krebs’ cycle.
The -Oxidation Pathway
Oxidation of un saturated fatty
acids
In polyunsaturated fatty acids the double bonds are in
cis geometry and occur at three carbon interval.
The intermediate in β oxidation have trans geometry
and the reaction proceeds in two carbon step.
 So the metabolism of unsaturated FA requires two
additional enzymes, - to shift the position, and
- to change the geometry of the double
bond.
Those enzymes are,
1. Isomerase - change the geometry of the double
bond.
2. Reductase - shift the position of the double bond.

Odd chain FA
Oxidation
Fatty acids with an odd number of carbon atoms are

oxidized by the pathway of β-oxidation, producing
acetyl-CoA, until a three-carbon residue, propionyl-
CoA
remains.
Then, propionyl-CoA is converted to succinyl-CoA,
which is,
a constituent of the citric acid cycle.
Oxidation of propionyl-CoA
Ketone Bodies
• Starvation causes accumulation of acetyl CoA

• not enough carbohydrates to keep Kreb’s Cycle going
• acetyl CoA forms acetoacetate, Bhydroxybutyrate, and acetone.
Ketone Bodies -
formed in the liver
and oxidized in
skeletal and heart
muscle and the renal
cortex. Brain adapts
to use them under
starvation conditions
Untreated diabetes,
severe dieting, fasting
promote
gluconeogenesis, slow
the citric cycle (by
drawing off
oxaloacetate) and
enhance the conversion
of acetyl-CoA to
acetoacetate.
Ketogenesis (Ketosis):
formation of Ketone Bodies *****
Thiolase
2 CH3COSCoA CH3COCH2COSCoA CH3COSCoA
Acetoacetyl CoA
HMG CoA
Synthase
Several
Cholesterol steps OH
(in cytosol)
HO2C-CH2-C-CH2COSCoA
CH3
(in liver: mitochon-
drial matrix) Ketogenesis -Hydroxy--methylglutaryl CoA
(HMG CoA)
Ketone body formation Ketone body oxidation
in liver Extrahepatic
tissue
in mitochondria
matrix
in cytosol for
cholesterol
synthesis
Oxidation of ketone bodies
in brain, muscle, kidney, and intestine
NAD+ Succinyl CoA synthetase = loss of GTP

NADH
-Hydroxybutyrate Acetoacetate
Succinyl CoA
-Hydroxybutyrate
dehydrogenase
CoA transferase Citric
CoA Acid
Cycle
Succinate
2 Acetyl CoA Acetoacetyl CoA
Thiolase
Diabetes and Ketone Bodies
• When there is not enough insulin in the blood and it
must break down fat for its energy.
• Ketones build up in the blood and then spill over into
the urine so that the body can get rid of them.
• Acetone can be exhaled through the lungs.
• This gives the breath a fruity odor.
• Ketones that build up in the body for a long time lead
to serious illness and coma. (Diabetic ketoacidosis ,
DKA)
Cont…
• Ketoacidosis results from prolonged ketosis:
• Ketonemia- higher than normal quantities of ketone
bodies in blood
• Ketonuria- higher than normal quantities of ketone
bodies in urine.
• Ketosis: the overall condition is called ketosis
• Sulfonylureas (glyburide and tolbutamide) inhibit
Carnitine palmitoyltransferase and reduce fatty acid
oxidation

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Beta oxidation of

fatty acids and

• The principal pathway for catabolism of fatty acids.

• Takes place in mitochondrial matrix of tissues in

and H2O takes place in 3 stages:

1. The oxidation of long-chain fatty acids to two-

fragments, in the form of acetyl-CoA, through β-

2. The oxidation of acetyl-CoA to CO2 in the citric acid

3. The transfer of electrons from reduced electron

There are four basic steps:

Step I: Unsaturation (dehydrogenation)

Catalyzed by acyl-CoA dehydrogenase & FAD.

Step II: Hydration

Catalyzed by enoyl-CoA Hydratase which helps

addition of H2O  to saturate double bond.

Dehydrogenation by -Hydroxy acyl CoA

Step IV : Splitting of active acetate-

- By Thiolase (acyl-CoA acetyl transferase)

shorter than the first one by 2 carbon atoms.

cis geometry and occur at three carbon interval.

The intermediate in β oxidation have trans geometry

and the reaction proceeds in two carbon step.

 So the metabolism of unsaturated FA requires two

additional enzymes, - to shift the position, and

- to change the geometry of the double

1. Isomerase - change the geometry of the double

2. Reductase - shift the position of the double bond.

Fatty acids with an odd number of carbon atoms are

• Starvation causes accumulation of acetyl CoA

NAD+ Succinyl CoA synthetase = loss of GTP

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