Degradation of TG
1 . Fat 2.β-Oxidation of
catabolism Fatty acids( fatty
(lipolysis) acid oxidation)
1.Fat catabolism (lipolysis)
Fat mobilization ：
The triacylglycerol stored in the adipocytes are
hydrolyzed by lipases, to produce free fatty acids
(FFA) and glycerol, which are released to the blood,
this process is called fat mobilization.
The fatty acids thus released diffusively from
the adipocyte into the blood, where they bind
to the serum albumin.
Regulation of hormone-sensitive TG-lipase
Lipase is present in an inactive form 'b' and is activated (phosphorylated) by a
cAMP dependent protein kinase to lipase 'a'.
Several hormones-such as epinephrine (most effective), norepinephrine,
glucagon, thyroxine, ACTH etc.- enhance the activity of adenylate cyclase and,
thus, increase lipolysis.
On the other hand, Insulin decreases cAMP levels and thereby inactivates lipase.
Caféine promotes lipolysis by Increasing cAMP levels through its inhibition on
Phosphodiesterase activity.
As is evident from the foregoing discussion, increased levels of cAMP promote
lipolysis.
In contrast, cAMP decreases fatty acid synthesis by inhibiting acetyl CoA
carboxylase activity.
lt should be therefore kept in mind that lipolysis and lipogenesis are not
simultaneously operative
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Effect of hormones on lipolysis
Lipolytic Hormones:
Epinephrine
Norepinephrine
Adrenocorticotropic hormone (ACTH)
Thyroid stimulating hormone (TSH)
Glucagon etc.
Antilipolytic Hormones: Insulin
Fate of glycerol
The adipose tissue lacks the enzyme glycerol kinase, hence glycerol
produced in lipolysis cannot be phosphorylated here.
lt is transported to liver where it is activated to glycerol 3- phosphate.
The latter may be used for the synthesis of triacylglycerols and
phospholipids.
Glycerol 3-phosphate may also enter glycolysis by getting converted to
dihydroxyacetone phosphate (Fig. 1 4.4).
Fate of free fatty acids
The fatty acids released by lipolysis in the adipocytes enter the Circulation
and are transported in a bound form to albumin.
The free fatty acids enter various tissues and are utilized for the energy.
About 95% of the energy obtained from fat comes from the oxidation of
fatty acids.
Certain tissues, however, cannot oxidize fatty acids, e.g. brain,
erythrocytes.
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2.Oxidation of Fatty acids:
(β-oxidation)
Fatty acids are one of the main energy materials of human
and other mammalian.
The fatty acids in the body are mostly oxidized by B-
oxidation.
β-Oxidation may be defined as the oxidation of fatty acids on
the β-carbon atom.
This results in the sequential removal of a two carbon
fragment, acetyl CoA
Fatty acid catabolism can be subdivided into 3 stages
I. Activation of fatty acids occurring in the
cytosol
ll. Transport of fatty acids into mitochondria;
lll. β-Oxidation proper in the mitochondrial matrix
Stage 1: Activation of FAs
Acyl-CoA Synthetase (Thiokinase), which locates on
the cytoplasm, catalyzes the activation of long chain
fatty acids.
ATP AMP + PPi
O O
Mg2+
R C + HSCoA R C
O acyl-CoA S CoA
synthetase
Fatty acid acyl-CoA
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.
Key points of FA activation
1. Irreversible
2. Consume 2 ~P
3. Site: cytosol
Stage 2
Transport of acyl CoA into the
mitochondria
( rate-limiting step)
Carrier: Carnitine
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 step
1. Acyl group of acyl CoA is transferred to carnitine , catalysed by
carnitine acyltransferase I (present on the outer surface of inner
mitochondrial membrane).
2. The acyl-carnitine is transported a cross 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.
Stage 3: β-oxidation of FAs
β-oxidation means β-C reaction.
Four steps in one round
step 1: Dehydrogenate
step 2: Hydration
step 3: Dehydrogenate
step 4: Thiolytic cleavage
Step 1. Dehydrogenate
H H O
H3 C (CH2)n C C C SCoA
H H Fatty acyl-CoA
FAD
acyl-CoA dehydrogenase
FADH2
H O
H3C (CH2)n C C C SCoA
H trans-¦¤2-enoyl-CoA
Step 2. Hydration
H O
H3C (CH2)n C C C SCoA
H Trans-¦¤2-enoyl-CoA
H2O
enoyl-CoA Hydratase
OH H O
H3C (CH2)n C C C SCoA
H H 3-L-Hydroxyacyl-CoA
Step 3. Dehydrogenate
OH H O
H3C (CH2)n C C C SCoA
H H 3-L-Hydroxyacyl-CoA
NAD+
hydroxyacyl-CoA
dehydrogenase
NADH + H+
O O
H3C (CH2)n C CH2 C SCoA
β-Ketoacyl-CoA
Step 4. Thiolytic cleavage
O O
H3C (CH2)n C CH2 C SCoA
β-Ketoacyl-CoA
HSCoA
β-Ketothiolase
O O
H3C (CH2)n C SCoA + CH3 C SCoA
Fatty acyl-CoA Acetyl-CoA
(2C shorter)
β- oxidation of fatty acids
The β-oxidation pathway is cyclic
Summary
One cycle of the β-oxidation:
fatty acyl-CoA + FAD + NAD+ + HS-CoA →fatty acyl-CoA (2
C less) + FADH2 + NADH + H+ + acetyl-CoA
FADH2= 2 ATP
NADH2+ 3ATP
Energy yield from one molecule of palmitic acid
palmitic acid 7¡Á2
-2 ~P activation respiratory chain
palmitoyl-CoA 8 acetyl CoA + 7 FADH2 + 7 NADH + 7 H+
7 turns of
¦Â-oxidation
TAC respiratory chain
8¡Á12
7¡Á3
The net ATP production: 131 － 2 = 129
