Oxidation of Fatty Acids.

Digestion of Triacylglycerols
Beta-Oxidation of Fatty Acids
ATP and Fatty Acid Oxidation

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The body fat is our major source of
stored energy.
 Our adipose tissue is made of
fat cells adipocytes.
 A typical 70 kg (150 lb) person
has about 135,000 kcal of
energy stored as fat, 24,000
kcal as protein, 720 kcal as
glycogen reserves, and 80 kcal
as blood glucose.
 The energy available from
stored fats is about 85 % of the
total energy available in the
body.

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 Digestion of Triacylglycerols
In the digestion of fats (triacylglycerols):
 Bile salts break fat globules into micelles in the small intestine.
 Pancreatic lipases hydrolyze ester bonds to form
monoacylglycerols and fatty acids, which recombine in the
intestinal lining.
 Lipoproteins form and transport triacylglycerols to the cells of
the heart, muscle, and adipose tissues.
 Brain and red blood cells cannot utilize fatty acids, because
fatty acids cannot diffuse across the blood-brain barrier, and
red blood cells have no mitochondria, where fatty acids are
oxidized. (Glucose and glycogen are the only source of energy
for the brain and red blood cells.)

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Digestion of Triacylglycerols

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 Fat Mobilization
Fat mobilization:
 Breaks down triacylglycerols in adipose
tissue to fatty acids and glycerol.
 Occurs when hormones glucagon and
epinephrine are secreted into the
bloodstream and bind to the receptors
on the membrane of adipose cells
activating the enzymes within the fat
cells that begin the hydrolysis of
triacylglycerols.
 Fatty acids are hydrolyzed initially from
C1 or C3 of the fat.
Lipases
Triacylglycerols +3H2O→Glycerol + 3Fatty acids

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Metabolism of Glycerol.
 Using two steps, enzymes in the liver convert glycerol to dihydroxyacetone phosphate,
which is an intermediate in several metabolic pathways including glycolysis and
gluconeogenesis.
 1st step: glycerol is phosphorylated using ATP to yield glycerol-3-phosphate.
 2nd step: the hydroxyl group is oxidized to yield dihydroxyacetone phosphate.
 The overall reaction for the metabolism of glycerol:
 Glycerol + ATP + NAD+ → Dihydroxyacetone phosphate + ADP + NADH + H+

H2C OH H2C OH H2C OH

Glycerol Glycerol-3-phosphate
kinase dehydrogenase
HC OH
H C OH C O

H2 C OH
ATP ADP H2 C OP
H2 C OP NAD+ NADH+H+

Glycerol Dihydroxyacetone
Glycerol-3-phosphate phosphate

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 Fatty Acid Activation
Fatty acid activation:
 Allows the fatty acids in the cytosol to enter the

mitochondria for oxidation.

 Combines a fatty acid with CoA to yield fatty

acyl CoA that combines with carnitine.

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 Fatty Acid Activation
 Fatty acyl-carnitine transports the fatty acid
into the matrix.
 The fatty acid acyl group recombines with
CoA for oxidation.

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 Fatty Acid Activation
 Fatty acid activation is complex, but it
regulates the degradation and synthesis of
fatty acids.

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 Beta-Oxidation of Fatty Acids
In reaction 1, oxidation:  
 Removes H atoms from the

 and  carbons.
 Forms a trans C=C bond.

 Reduces FAD to FADH .

2

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 Beta-Oxidation of Fatty Acids
In reaction 2, hydration: 
 Adds water across the

trans C=C bond.

 Forms a hydroxyl

group (—OH) on the 

carbon.

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 Beta ()-Oxidation of Fatty Acids
In reaction 3, a 
second oxidation:
 Oxidizes the hydroxyl
group.
 Forms a keto group
on the  carbon.

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 Beta ()-Oxidation of Fatty Acids
In Reaction 4, acetyl
CoA is cleaved:
 By splitting the bond
between the  and 
carbons.
 To form a shortened
fatty acyl CoA that
repeats steps 1 - 4 of
-oxidation.

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Beta ()-Oxidation of Myristic (C14)
Acid

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 Beta ()-Oxidation of Myristic (C14)
Acid (continued)

6 cycles 7 Acetyl
CoA

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 Cycles of -Oxidation
The length of a fatty acid:
 Determines the number of oxidations and
 The total number of acetyl CoA groups.
Carbons in Acetyl CoA -Oxidation Cycles
Fatty Acid (C/2) (C/2 –1)
12 6 5
14 7 6
16 8 7
18 9 8

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 -Oxidation and ATP
Activation of a fatty acid requires:
 2 ATP

One cycle of oxidation of a fatty acid produces:

 1 NADH 3 ATP
 1 FADH 2 ATP
2

Acetyl CoA entering the citric acid cycle produces:

 1 Acetyl CoA 12 ATP

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 ATP for Lauric Acid C12
ATP production for lauric acid (12 carbons):
Activation of lauric acid -2 ATP
6 Acetyl CoA
6 acetyl CoA x 12 ATP/acetyl CoA 72 ATP
5 Oxidation cycles
5 NADH x 3ATP/NADH 15 ATP
5 FADH2 x 2ATP/FADH2 10 ATP

Total 95 ATP
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Oxidation of Unsaturated Fatty
Acids.
 Oxidation of monounsaturated fatty acyl-CoA
requires additional reaction performed with the
help of the enzyme isomerase.
 Double bonds in the unsaturated fatty acids are in
the cis configuration and cannot be acted upon by
enoyl-CoA hydratase (the enzyme catalyzing the
addition of water to the trans double bond
generated during β-oxidation.
 Enoyl-CoA isomerase repositions the double
bond, converting the cis isomer to trans isomer, a
normal intermediate in β-oxidation.

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Oxidation of polyunsaturated fatty
acids.
 Requires two additional reactions and a
second enzyme, reductase, in addition to
isomerase.
 NADPH-dependent 2,4-dienoyl-CoA
reductase converts trans-2, cis-4-dienoyl-
CoA intermediate into the trans-2-enoyl-
CoA substrate necessary for β-oxidation.

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Oxidation of odd-chain fatty acids.
 Odd-carbon fatty acids are oxidized by the same pathway as even-
carbon acids until three-carbon propionyl-CoA is formed.
 After that, three additional reactions are required involving three
enzymes.
 Propionyl-CoA is carboxylated by propionyl-CoA carboxylase (with
the cofactor biotin) to form the D stereoisomer of methylmalonyl-
CoA (The formation of the carboxybiotin intermediate requires energy
from ATP).
 D-methylmalonyl-CoA is changed into L-methylmalonyl-CoA by
methylmalonyl-CoA epimerase.
 L-methylmalonyl-CoA undergoes an intramolecular rearrangment to
form succinyl-CoA, which enters the citric acid cycle. This
rearrangment is catalyzed by methylmalonyl-CoA mutase, which
requires coenzyme B12, derived from vitamin B12 (cobalamin).

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 Overview of Metabolism
In metabolism:
 Catabolic pathways degrade large molecules.

 Anabolic pathway synthesize molecules.

 Branch points determine which compounds are

degraded to acetyl CoA to meet energy needs or

converted to glycogen for storage.

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