FATTY ACID OXIDATION
Dr KW Poopedi.
Department of Biochemistry, Microbiology
and Biotechnology, University of Limpopo,
Private Bag x 1106, Sovenga 0727
Polokwane, South Africa
β-oxidation of fatty acid
• Β-oxidation of fatty acid is the catabolic
process by which fatty acid molecules are
broken down to generate acetyl-CoA
• Type of reaction: catabolic reaction
• Site of reaction: mitochondrial
matrix/peroxisomes
•
•
•
•
Acyl-CoA dehydrogenase
Enoyl-CoA hydratase
L-Hydroxyacyl-CoA
Thiolase
Acyl-CoA
(myristoyl-CoA)
+
β-oxidation of fatty acid
• Where does beta-oxidation take place?
• Under what conditions does betaoxidation take place?
• What are the enzymes for beta-oxidation?
Under what conditions does beta-oxidation take place?
FATTY ACID SYNTHESIS/ANABOLISM
FATTY ACID OXIDATION/CATABOLISM
FED STATE
FASTED STATE
Under what conditions does beta-oxidation take place?
How are fatty acids transported to the mitochondria?
• Fatty acids are activated before they are transported to the
mitochondria? What does activation pertain to?
• Fatty acids are linked to coenzyme A before they are oxidized.
• They are activated through the formation of thioester bond
linkage between the carboxyl group of a fatty acid and
sulfhydryl group of coenzyme A.
• This activation takes place on the outer mitochondrial
membrane, where it is catalyzed by acyl CoA synthetase (ATP
is used in this process)
Fatty acids activation
How are fatty acids transported to the mitochondria?
Palmitoyl carnitine
cytosol
Inter membrane space
matrix
How are fatty acids transported to the mitochondria?
How are fatty acids transported to the mitochondria?
How are fatty acids transported to the mitochondria?
How are fatty acids transported to the mitochondria?
Beta –oxidation of fatty acids
Beta –oxidation of fatty acids
Beta –oxidation of fatty acids
Beta –oxidation of fatty acids
ATP yield in beta-oxidation
• How many ATP molecules are generated
during the complete oxidation of fatty acids in
the matrix of the mitochondria?
• In the α-oxidation pathway, each round of
oxidation yields one molecule of acetyl-CoA.
Palmitic acid has 16 carbon atoms, so it
requires multiple rounds of α-oxidation to
completely break it down.
ATP yield in beta-oxidation
• First, let's start with β-oxidation. Palmitic
acid has 16 carbon atoms, so it requires 7
rounds of β-oxidation to break it down into
8 molecules of acetyl-CoA.
ATP yield in beta-oxidation
• Six 6 cycles of Beta oxidation give us
Ketoacyl CoA and 6 acetyl-CoA.
• Ketoacyl CoA/acetoacetyl CoA when it undergoes beta
oxidation then we get 2 acetyl Co-A molecules.
• In total there are 8 acetyl CoA
Ketoacyl-CoA
C4
β-oxidation
+
6 cycles
6 acetyl-CoA
6 Acetyl-CoA
2 acetyl-CoA
8 acetyl-CoA
ATP yield in beta-oxidation
• Let n represent the number of carbons
n/2 (16/2)= 8 acetyl-CoA
n/2-1 (8-1)=7 cycles
ATP yield in beta-oxidation
• Each molecule of FADH2 formed during oxidation of
the fatty acid donates a pair of electrons to ETF of the
respiratory chain, and about 1.5 molecules of ATP are
generated during the ensuing transfer of each electron
pair to O2
• Similarly, each molecule of NADH formed delivers a
pair of electrons to the mitochondrial NADH
dehydrogenase, and the subsequent transfer of each pair
of electrons to O2 results in formation of about 2.5
molecules of ATP. Thus four molecules of ATP are
formed for each two-carbon unit removed in one pass
through the sequence.
ATP yield in beta-oxidation
8x( 3NADH + FADH2 + GTP)= 24 NADH + 8 FADH2 +8 GTP
8 (During the citric acid cycle (also
known as the Krebs cycle or TCA
cycle), each acetyl-CoA is fully
oxidised and produces 3 molecules
of NADH, 1 molecule of FADH2,
and 1 molecule of GTP (which can
be converted to ATP).
• Remember FADH2 = 1.5 ATP
• NADH = 2.5 ATP
• GTP= 1ATP
• Calculate: 8 acetyl CoA X (3NADH +
FADH + GTP)
• Add up:
MCQ
1.22 What is the net gain of ATP/mol of palmitic acid on complete oxidation?
In the α-oxidation pathway, each round of oxidation yields one molecule of acetyl-CoA.
Palmitic acid has 16 carbon atoms, so it requires multiple rounds of α-oxidation to completely
break it down.
1.First, let's start with β-oxidation. Palmitic acid has 16 carbon atoms, so it requires 7 rounds
of β-oxidation
7 FADH2 + 7 NADH
2.Palmitic acid is broken down into 8 molecules of acetyl-CoA.
8 Acetyl-CoA is then oxidized in the CAC + 7FADH2+ 7NADH
During the citric acid cycle (also known as the Krebs cycle or TCA cycle), each acetyl-CoA is
fully oxidized and produces 3 molecules of NADH, 1 molecule of FADH2, and 1 molecule of GTP
(which can be converted to ATP).
Remember FADH2 = 1.5 ATP
NADH = 2.5 ATP
GTP= 1ATP
1. Let n represent the number of carbons
• how many acetyl coA?
n/2 (16/2) =8
• how many cycles?
n/2-1 (8-1)=7
Calculate: 8 acetyl CoA X (3NADH + FADH + GTP)
= 24 NADH + 8 FADH + 8 GTP
Tally: 8 FADH2 + 7 FADH2 + 24 NADH+ 7 NADH + 8 GTP (ATP)
=15 FADH2 x 1.5 + 31 NADHx2.5 + 8 ATP x1
=22.5 +77.5 +8.0
108 -2 ATP used in the activation of palmitic acid
Answer= 106
Poopedi KW Carbohydrate metabolism 2023
25
Ketone Bodies
Metabolism, Formation, and
Clinical Significance
Introduction
• Ketone bodies are substances related to
acetone.
• Produced when excess acetyl-CoA arises
from β-oxidation.
• Occurs when oxaloacetate is insufficient to
react with acetyl-CoA.
• Common in starvation, diabetes, and highfat low-carb diets.
Formation of Ketone Bodies
• Begins with condensation of two acetylCoA → acetoacetyl-CoA.
• Acetoacetyl-CoA + acetyl-CoA → HMGCoA.
• HMG-CoA lyase → acetoacetate.
• Acetoacetate → β-hydroxybutyrate
(reduction).
• Acetoacetate → acetone (spontaneous
decarboxylation).
Clinical Significance
• Excess acetoacetate & acetone → ketosis.
• Acidity of ketone bodies → ketoacidosis.
• Symptoms: acetone breath, dehydration,
excessive thirst.
• Severe cases: diabetic coma.
Utilisation of Ketone Bodies
• Synthesized in liver mitochondria but not
used there.
• Water-soluble, easily transported in blood.
• Used by heart, renal cortex, and brain
(during starvation).
• Converted to acetyl-CoA → citric acid
cycle.
Hormonal & Metabolic Regulation
• Long-term regulation during starvation.
• Low blood glucose → hormonal changes
(insulin ↓, glucagon ↑).
• Increases fatty acid oxidation enzymes.
• Decreases lipid biosynthesis enzymes.
• Alters protein synthesis and breakdown.
Ketone bodies
Ketone bodies