Oxidation of Fatty Acids.

Digestion of Triacylglycerols
Beta-Oxidation of Fatty Acids
ATP and Fatty Acid Oxidation
1

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.

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.)
3

Digestion of Triacylglycerols

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 +3H2OGlycerol + 3Fatty acids

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

HC

OH

H2 C

OH

Glycerol

H2C

OH

Glycerol-3-phosphate
dehydrogenase

Glycerol
kinase

ATP ADP

H2C

OH

H2 C

OH

OP

Glycerol-3-phosphate

NAD+

NADH+H+

H2 C

OP

Dihydroxyacetone
phosphate

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.

Fatty Acid Activation

Fatty acyl-carnitine transports the fatty acid

into the matrix.
The fatty acid acyl group recombines with CoA
for oxidation.

Fatty Acid Activation

Fatty acid activation is complex, but it

regulates the degradation and synthesis of
fatty acids.

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

10

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.

11

Beta ( )-Oxidation of Fatty Acids

In reaction 3, a
second oxidation:
Oxidizes the hydroxyl
group.
Forms a keto group
on the carbon.

12

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.
13

Beta ( )-Oxidation of Myristic (C14)

Acid

14

Beta ( )-Oxidation of Myristic (C14)

Acid (continued)

6 cycles

7 Acetyl
CoA

15

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
16

-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

17

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
18

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 -oxidation.
Enoyl-CoA isomerase repositions the double bond,
converting the cis isomer to trans isomer, a normal
intermediate in -oxidation.
19

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-dienoylCoA intermediate into the trans-2-enoylCoA substrate necessary for -oxidation.
20

Oxidation of odd-chain fatty acids.

Odd-carbon fatty acids are oxidized by the same pathway as evencarbon 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 methylmalonylCoA (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).

21

22

23

24

25

26

27

28

29

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.

30

31