Beta Oxidation of Fatty Acids

Saturated and Unsaturated Fatty Acids

MUFA and PUFA
 Fatty Acid Oxidation

is the primary source of energy for many tissues

with the exception of the central nervous system
and circulating RBC
 Process by which fatty acids are
broken down to obtain energy:
• The fatty acid must be activated
• The fatty acid must be transported into the
mitochondrial matrix by a shuttle mechanism
• The fatty acid must be repeatedly oxidized,
cycling thru a series of 4 reactions, to
produce acetyl CoA, FADH2 and NADH
Triglyceride
Fatty Acid Structure
 Overview of Beta Oxidation

Adipose Tissue
 Breaking down Triglycerides
• When the body requires fatty acids as an energy
source, the hormone in the body signals the
breakdown of the triglycerides by the enzyme lipase
to release free fatty acids.
• Triacylglycerol mobilization is the hydrolysis of
triacylglycerols stored in adipose tissue
 Free fatty acids are negatively charged
molecules. How does it pass thru the cell
membrane?
Fatty acids are able to enter the
target cell on where it will be
synthesized with the use of a
Fatty acid transporter
 Saturated Fatty Acid

■ Lauric (dodecanoic acid): CH3(CH2)10COOH or C12:0

■ Myristic (tetradecanoic acid): CH3(CH2)12COOH or C14:0
■ Palmitic (hexadecanoic acid): CH3(CH2)14COOH or C16:0
■ Stearic (octadecanoic acid): CH3(CH2)16COOH or C18:0
■ Arachidic (eicosanoic acid): CH3(CH2)18COOH or C20:0
■ Behenic (docosanoic acid): CH3(CH2)20COOH or C22:0
 Unsaturated Fatty Acid
■ Oleic acid: CH3(CH2)7CH=CH(CH2)7COOH or cis-Δ9 C18:1
■ Linoleic acid: CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH or C18:2
■ Alpha-linolenic acid:
CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH or C18:3
■ Arachidonic acid
CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH
or C20:4
■ Eicosapentaenoic acid or C20:5
■ Docosahexaenoic acid or C22:6
 Fatty Acid Activation
(First stage of FA oxidation)

Site : Outer Mitochondrial Membrane

Reactants : Fatty acid, CoA and ATP
Enzyme : Acyl CoA Synthase
Fatty acid is converted to Acyl CoA
Activated Fatty Acid CoA : Acyl CoA
This reaction requires the expenditure of two high-energy
phosphate bonds from a single ATP molecule; the ATP is
converted to AMP rather than ADP, and the resulting
pyrophosphate (PPi ) is hydrolyzed to 2Pi .
 Fatty Acid Transport
• Acyl CoA is too large to pass through the inner mitochondrial
membrane to the mitochondrial matrix, where the enzymes
needed for fatty acid oxidation are located. A shuttle
mechanism involving the molecule carnitine allows the entry
of acyl CoA into the matrix. The acyl group is transferred to a
carnitine molecule, which carries it through the membrane.
The acyl group is then transferred from the carnitine back to a
CoA molecule.
Regulation of Carnitine Shuttle

● This carnitine shuttle is a rate limiting step in the

oxidation of fatty acids in the mitochondria and thus
fatty acid oxidation can be regulated at this step.
● Malonyl CoA, an intermediate of fatty acid synthesis
present in the cytosol is an inhibitor of carnitine
acyltransferase I. This indicates that when fatty acid
synthesis is in progress, oxidation of fatty acid cannot
occur at the same time as the carnitine shuttle is
impaired by inhibition of carnitine acyltransferase I.
 Beta-oxidation pathway
• A repetitive series of four biochemical
reactions degrading Acyl CoA to Acetyl CoA by
removing two carbon atoms at a time, with
FADH2 and NADH also being produced. Each
repetition of the four-reaction sequence
generates an Acetyl CoA molecule and an Acyl
CoA molecule that has two fewer carbon atoms.
For a saturated fatty acid, the b-oxidation pathway involves
the following functional group changes at the b carbon and
the following reaction types.
Beta Oxidation of Saturated Fatty Acids
 Step 1: Oxidation (dehydrogenation)
Hydrogen atoms are removed from the a and b carbons,
creating a double bond between these two carbon atoms.
FAD is the oxidizing agent, and a FADH2 molecule is a
product. Enzyme : Acyl CoA Dehydrogenase (Stereospecific)
 Step 2: Hydration
A molecule of water is added across the trans double bond,
producing a secondary alcohol at the b-carbon position.
Again, the enzyme involved is stereospecific in that only the L-
hydroxy isomer is produced from the trans double bond.
Enzyme : Enoyl CoA Hydratase
 Step 3: Oxidation (dehydrogenation).
The beta-hydroxy group is oxidized to a ketone functional
group with NAD+ serving as the oxidizing agent. The required
enzyme exhibits absolute stereospecificity for the L-isomer.
Enzyme : B-hydroxyacyl CoA Dehydrogenase
 Step 4: Chain Cleavage
The fatty acid chain is broken between the a and b carbons by
reaction with a coenzyme A molecule. The result is an acetyl
CoA molecule and a new acyl CoA molecule that is shorter by
two carbon atoms than its predecessor.
Enzyme : Thiolase
The new acyl CoA molecule (now shorter by two
carbons) is recycled through the same set of four
reactions again. This yields another acetyl CoA, a two-
carbon-shorter new acyl CoA, FADH2, and NADH.
Recycling occurs again and again, until the entire
fatty acid is converted to acetyl CoA. Thus the fatty
acid carbon chain is sequentially degraded, two
carbons at a time
The number of acetyl CoA molecules produced in the b-oxidation
pathway is equal to half the number of carbon atoms in the fatty
acid.
Acetyl CoA Molecules = no. of C-atoms FA/2
The number of repetitions of the b-oxidation pathway that are
needed to produce the acetyl CoA is always one less than the
number of acetyl CoA molecules produced
B-Oxidation cycle = no. of Acetyl CoA - 1
The number of FADH2 and NADH molecules produced are equal to
the number of repetitions of the Beta-oxidation cycle
B-Oxidation cycle = no. of FADH2 and NADH
 ATP YIELD IN SATURATED FATTY ACIDS
9 repetitions of the B-oxidation pathway are required for the
oxidation of Behenic (docosanoic acid) or C20 fatty acid.
These 9 repetitions of the pathway produce 10 acetyl CoA
molecules, 9 FADH2 molecules, and 9 NADH molecules. It is
processed further in common metabolic pathway (citric acid cycle,
electron transport chain, and oxidative phosphorylation) leads to
ATP production as follows:
10 Acetyl CoA x 10 ATP/Acetyl CoA = 100 ATP
9 NADH x 3ATP/NADH = 27 ATP
9 FADH2 x 2ATP/FADH2 = 18 ATP
TOTAL ATP YIELD : 145 ATP
Beta Oxidation of Unsaturated Fatty Acids
Unsaturated Fatty Acid Beta-oxidation
β-oxidation pathway for unsaturated fatty
acids includes two additional enzymes
isomerase and reductase. It still follows
the four repetitive steps much like how
saturated fatty acids are oxidized.
Just like the saturated fatty acids cross
the mitochondrial membrane with the
help of carnitine shuttle. Unsaturated
fatty acids also reach the mitochondrial
matrix as fatty acyl-CoA.
β-oxidation of oleic acid (MUFA) by the enzymes present in the mitochondrial
matrix is as shown:
β-oxidation of linoleic acid (PUFA) by the enzymes present in the
mitochondrial matrix is as shown:
 Unsaturated Fatty Acid Oxidation
THE SAME IS TRUE WITH UNSATURATED FATTY ACID
OXIDATION:

Acetyl CoA Molecules = no. of C-atoms FA/2

B-Oxidation cycle = no. of Acetyl CoA - 1
B-Oxidation cycle = no. of FADH2 and NADH
 ATP YIELD IN UNSATURATED FATTY ACIDS (OLEIC ACID)
8 repetitions of the B-oxidation pathway are required for the
oxidation of Oleic Acid or C18 fatty acid.
These 8 repetitions of the pathway produce 9 acetyl CoA
molecules, 8 FADH2 molecules, and 8 NADH molecules. It is
processed further in common metabolic pathway (citric acid cycle,
electron transport chain, and oxidative phosphorylation) leads to
ATP production as follows:
9 Acetyl CoA x 10 ATP/Acetyl CoA = 90 ATP
8 NADH x 3ATP/NADH = 24 ATP
8 FADH2 x 2ATP/FADH2 = 16 ATP
TOTAL ATP YIELD : 130 ATP
 ATP YIELD IN UNSATURATED FATTY ACIDS (LINOLEIC ACID)
8 repetitions of the B-oxidation pathway are required for the
oxidation of Linoleic Acid or C18 fatty acid.
These 8 repetitions of the pathway produce 9 acetyl CoA
molecules, 8 FADH2 molecules, and 8 NADH molecules. It is
processed further in common metabolic pathway (citric acid cycle,
electron transport chain, and oxidative phosphorylation) leads to
ATP production as follows:
9 Acetyl CoA x 10 ATP/Acetyl CoA = 90 ATP
8 NADH x 3ATP/NADH = 24 ATP
8 FADH2 x 2ATP/FADH2 = 16 ATP
TOTAL ATP YIELD : 130 ATP
 Beta Oxidation Overall Reaction

Cn-acyl-CoA + FAD + (NAD+) + H2O +

CoA-SH
→
Cn-acyl-CoA + FADH2 + NADH + (H+) +
acetyl-CoA