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Beta-oxidation of Fatty Acid
Anup Muni Bajracharya
• Lipids are esters of fatty acids with alcohol. ...
• Triglycerides are esters of fatty acids with glycerol
• They are called triglycerides because they are
formed of glycerol and 3 fatty acids.
LIPIDS
A.B
A.B
Oxidation of Fatty Acids
• Fatty acids are oxidized by β-, α- and ω-oxidation.
• Quantitatively, β-oxidation is the most important pathway.
• The term β-oxidation means the oxidation takes place in the β-carbon of
the fatty acid with the removal of 2 carbon atoms at a time from the
carboxyl end of the molecule.
• The fatty acids containing even number and odd number of carbon atoms
as well as the unsaturated fatty acids are oxidized by β-oxidation.
The last
carbon is
considered
as omega
A.B
Beta-oxidation
• Beta-oxidation is the catabolic
process by which fatty
acid molecules are broken down in
the cytosol in prokaryotes and in
the mitochondria in eukaryotes to
generate acetyl-CoA.
• Acetyl-CoA enters the citric acid
cycle while NADH and FADH2, which
are co-enzymes, are used in
the electron transport chain.
• It is referred as “beta oxidation”
because the beta carbon of the fatty
acid undergoes oxidation to
a carbonyl group.
A.B
Location
• Beta-Oxidation takes place in the mitochondria of
eukaryotes while in the cytosol in the prokaryotes.
• Substrates: Free fatty acids; H2O.
• Products: One acetyl CoA, one NADH, and one
FADH2 for every removal of a two-carbon group from
the fatty acid chain.
A.B
Steps
The Beta-oxidation of fatty acids involves three
stages
I. Activation of fatty acids occurring in the
cytosol
II. Transport of fatty acids into mitochondria
III. Beta-Oxidation proper in the mitochondrial
matrix.
A.B
Step I: Activation of fatty acid
• Fatty acids are activated to acyl
CoA by thiokinases or acyl CoA
synthetases.
• The reaction occurs in two steps
and requires ATP, coenzyme A and
Mg2+.
• Fatty acid reacts with ATP to form
acyladenylate which then
combines with coenzyme A to
produce acyl CoA.
• In the activation, two high energy
phosphates are utilized, since ATP
is converted to pyrophosphate
(PPi).
• The enzyme inorganic
pyrophosphatase hydrolyses PPi to
phosphate (Pi).
• The immediate elimination of PPi
makes this reaction totally
irreversible
A.B
Step II: Transport of acetyl coA into mitochondria
A.B
Step II: Transport of acetyl coA into mitochondria
• The inner mitochondrial membrane is impermeable to fatty acids.
• A specialized carnitine carrier system (carnitine shuttle) operates to
transport activated fatty acids from cytosol to the mitochondria.
• This occurs in four steps.
• 1. Acyl group of acyl CoA is transferred to carnitine, catalysed by carnitine
acyl transferase (present on the outer surface of inner mitochondrial
membrane).
• 2. The acyl-carnitine is transported across the membrane to mitochondrial
matrix by a specific carrier protein.
• 3. Carnitine acyl transferase ll (found on the inner surface of inner
mitochondrial membrane) converts acyl-carnitine to acyl CoA.
• 4. The carnitine released returns to cytosol for reuse.
A.B
Step III: β oxidation proper
Each cycle of β -oxidation,
liberating a two carbon
unit-acetyl CoA, occurs in a
sequence of four reactions.
1. Oxidation : Acyl CoA
undergoes
dehydrogenation by FAD-
dependent flavoenzyme,
acyl CoA dehydrogenase. A
double bond is formed
between o and β carbons
(i.e.,2 and 3 carbons).
2. Hydration : Enoyl CoA
hydratase brings about the
hydration of the double
bond to form β -
hydroxyacyl CoA.
A.B
3. Oxidation : β -Hydroxyacyl CoA
dehydrogenase catalyses the second
oxidation and generates NADH. The
product formed is β -ketoacyl CoA.
4. Cleavage : The final reaction in β -
oxidation is the liberation of a 2 carbon
fragment, acetyl CoA from acyl CoA.
This occurs by a thiolytic cleavage
catalysed by β -ketoacyl CoA thiolase (or
simply thiolase). The new acyl CoA,
containing two carbons less than the
original, reenters the β -oxidation cycle.
The process continues till the fatty acid is
completely oxidized.
Step III: β oxidation proper
A.B
ATP produced in beta oxidation of palmitic acid
• Palmitic acid, or hexadecanoic acid is the most
common saturated fatty acid found in animals,
plants and microorganisms.
• Its chemical formula is CH3(CH2)14COOH.
• It is a major component of the oil from the
fruit of oil palms (palm oil).
• β-oxidation of palmitic acid will be repeated 7
cycles producing 8 molecules of acetyl COA.
A.B
Calculation
In each cycle FADH2 and NADH+H+ is produced and
will be transported to the respiratory chain.
• FADH2 2 ATP
• NADH + H+ 3 ATP
So 7 cycles 5x7 = 35 ATP
Each acetyl COA which is oxidized in citric acid cycle
(TCA Cycle) gives 12 ATP (8 x 12 = 96 ATP)
2 ATP are utilized in the activation of fatty acid (It
occurs once).
Total Energy gain = 35 ATP + 96 ATP - 2 ATP = 129 ATP
A.B
A.B

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Beta oxidation of fatty acid

  • 1. Beta-oxidation of Fatty Acid Anup Muni Bajracharya
  • 2. • Lipids are esters of fatty acids with alcohol. ... • Triglycerides are esters of fatty acids with glycerol • They are called triglycerides because they are formed of glycerol and 3 fatty acids. LIPIDS A.B
  • 3. A.B
  • 4. Oxidation of Fatty Acids • Fatty acids are oxidized by β-, α- and ω-oxidation. • Quantitatively, β-oxidation is the most important pathway. • The term β-oxidation means the oxidation takes place in the β-carbon of the fatty acid with the removal of 2 carbon atoms at a time from the carboxyl end of the molecule. • The fatty acids containing even number and odd number of carbon atoms as well as the unsaturated fatty acids are oxidized by β-oxidation. The last carbon is considered as omega A.B
  • 5. Beta-oxidation • Beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. • Acetyl-CoA enters the citric acid cycle while NADH and FADH2, which are co-enzymes, are used in the electron transport chain. • It is referred as “beta oxidation” because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. A.B
  • 6. Location • Beta-Oxidation takes place in the mitochondria of eukaryotes while in the cytosol in the prokaryotes. • Substrates: Free fatty acids; H2O. • Products: One acetyl CoA, one NADH, and one FADH2 for every removal of a two-carbon group from the fatty acid chain. A.B
  • 7. Steps The Beta-oxidation of fatty acids involves three stages I. Activation of fatty acids occurring in the cytosol II. Transport of fatty acids into mitochondria III. Beta-Oxidation proper in the mitochondrial matrix. A.B
  • 8. Step I: Activation of fatty acid • Fatty acids are activated to acyl CoA by thiokinases or acyl CoA synthetases. • The reaction occurs in two steps and requires ATP, coenzyme A and Mg2+. • Fatty acid reacts with ATP to form acyladenylate which then combines with coenzyme A to produce acyl CoA. • In the activation, two high energy phosphates are utilized, since ATP is converted to pyrophosphate (PPi). • The enzyme inorganic pyrophosphatase hydrolyses PPi to phosphate (Pi). • The immediate elimination of PPi makes this reaction totally irreversible A.B
  • 9. Step II: Transport of acetyl coA into mitochondria A.B
  • 10. Step II: Transport of acetyl coA into mitochondria • The inner mitochondrial membrane is impermeable to fatty acids. • A specialized carnitine carrier system (carnitine shuttle) operates to transport activated fatty acids from cytosol to the mitochondria. • This occurs in four steps. • 1. Acyl group of acyl CoA is transferred to carnitine, catalysed by carnitine acyl transferase (present on the outer surface of inner mitochondrial membrane). • 2. The acyl-carnitine is transported across the membrane to mitochondrial matrix by a specific carrier protein. • 3. Carnitine acyl transferase ll (found on the inner surface of inner mitochondrial membrane) converts acyl-carnitine to acyl CoA. • 4. The carnitine released returns to cytosol for reuse. A.B
  • 11. Step III: β oxidation proper Each cycle of β -oxidation, liberating a two carbon unit-acetyl CoA, occurs in a sequence of four reactions. 1. Oxidation : Acyl CoA undergoes dehydrogenation by FAD- dependent flavoenzyme, acyl CoA dehydrogenase. A double bond is formed between o and β carbons (i.e.,2 and 3 carbons). 2. Hydration : Enoyl CoA hydratase brings about the hydration of the double bond to form β - hydroxyacyl CoA. A.B
  • 12. 3. Oxidation : β -Hydroxyacyl CoA dehydrogenase catalyses the second oxidation and generates NADH. The product formed is β -ketoacyl CoA. 4. Cleavage : The final reaction in β - oxidation is the liberation of a 2 carbon fragment, acetyl CoA from acyl CoA. This occurs by a thiolytic cleavage catalysed by β -ketoacyl CoA thiolase (or simply thiolase). The new acyl CoA, containing two carbons less than the original, reenters the β -oxidation cycle. The process continues till the fatty acid is completely oxidized. Step III: β oxidation proper A.B
  • 13. ATP produced in beta oxidation of palmitic acid • Palmitic acid, or hexadecanoic acid is the most common saturated fatty acid found in animals, plants and microorganisms. • Its chemical formula is CH3(CH2)14COOH. • It is a major component of the oil from the fruit of oil palms (palm oil). • β-oxidation of palmitic acid will be repeated 7 cycles producing 8 molecules of acetyl COA. A.B
  • 14. Calculation In each cycle FADH2 and NADH+H+ is produced and will be transported to the respiratory chain. • FADH2 2 ATP • NADH + H+ 3 ATP So 7 cycles 5x7 = 35 ATP Each acetyl COA which is oxidized in citric acid cycle (TCA Cycle) gives 12 ATP (8 x 12 = 96 ATP) 2 ATP are utilized in the activation of fatty acid (It occurs once). Total Energy gain = 35 ATP + 96 ATP - 2 ATP = 129 ATP A.B
  • 15. A.B