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ß Oxidation of fatty acids
1. ß-OXIDATION OF FATTY ACIDS
AND BIOENERGETICS OF ß
OXIDATION
Farah Rafat 15181514-044
Najam UL Sehar Aiman 15181514-040
Azra Sahnawaz 15151514-041
2. Introduction
■ lipids are stored in the .form of lipid droplets
■ The surface of these droplets is coated with perilipins, a family of proteins
that restrict access to lipid droplets.
3. Mobilization of triacylglycerols stored in adipose tissue.
■ the hormone binds its receptor in the adipocyte membrane and thus
■ stimulates adenylyl cyclase, via a G protein, to produce cAMP. This
activates PKA, which phosphorylates
■ the hormone-sensitive lipase and
■ perilipin molecules on the surface of the lipid droplet. Phosphorylation of
perilipin permits hormone sensitive lipase access to the surface of the lipid
droplet, where
■ it hydrolyzes triacylglycerols to free fatty acids.
■ Fatty acids leave the adipocyte, bind serum albumin in the blood, and are
carried in the blood; they are released from the albumin and
■ enter a myocyte via a specific fatty acid transporter.
■ In the myocyte, fatty acids are oxidized to CO2, and the energy of oxidation
is conserved in ATP, which fuels muscle contraction and other energy
requiring metabolism in the myocyte.
4.
5. Conversion of a fatty acid to a fatty
acyl–CoA
■ The conversion is catalyzed by fatty acyl–CoA synthetase and inorganic
pyrophosphatase. Fatty acid activation by formation of the fatty acyl–CoA
derivative occurs in two steps. In step
■ 1, the carboxylate ion displaces the outer two (ß and𝛾 ) phosphates of ATP
to form a fatty acyl–adenylate, the mixed anhydride of a carboxylic acid and
a phosphoric acid. The other product is PPi, an excellent leaving group that
is immediately hydrolyzed to two Pi, pulling the reaction in the forward
direction. In step
■ 2, the thiol group of coenzyme A carries out nucleophilic attack on the
enzyme-bound mixed anhydride, displacing AMP and forming the thioester
fatty acyl–CoA. The overall reaction is highly exergonic.
6.
7. Major Fatty Acid Oxidation = β-Oxidation Occurs
in the Mitochondrion
The activation occurred in the cytoplasm, but fatty acid
oxidation takes place in the mitochondria. The details are
not so important as knowing that this is the Carnitine
shuttle to get the fatty acid in as acyl-S-CoA. Now we are
ready for β-oxidation.
8. β-Oxidation
Overall Flow
Stages of fatty acid oxidation.
Stage 1:
A long-chain fatty acid is oxidized to yield
acetyl residues in the form of acetylCoA.
This process is called ß oxidation.
Stage 2:
The acetyl groups are oxidized to CO2 via
the citric acid cycle.
Stage 3
: Electrons derived from the oxidations of
stages 1 and 2 pass to O2 via the
mitochondrial respiratory chain, providing
the energy for ATP synthesis by oxidative
phosphorylation
9. The ß -oxidation pathway of saturated
fatty acids.
■ .(a) In each pass through this four-step sequence, one acetyl residue
(shaded in pink) is removed in the form of acetyl-CoA from the carboxyl end
of the fatty acyl chain— in this example palmitate (C16), which enters as
palmitoyl-CoA.
■ (b) Six more passes through the pathway yield seven more molecules of
acetyl-CoA, the seventh arising from the last two carbon atoms of the 16-
carbon chain. Eight molecules of acetyl-CoA are formed in all.
10. 2 Systems for b-oxidation
• ≥ 12 carbons:
• TFP – last 3 enzymes in
multi enzyme complex
• < 12 carbons
• 4 soluble matrix
enzymes
11. Oxidation of a monounsaturated fatty
acid.
Oleic acid, as oleoyl-CoA (∆9), is the
example used here. Oxidation requires
an additional enzyme, enoyl-CoA
isomerase, to reposition the double
bond, converting the cis isomer to a
trans isomer, a normal intermediate in ß
oxidation.
12. Oxidation of a
polyunsaturated
fatty acid.
The example here is linoleic
acid, as linoleoyl-CoA
(∆9.12). Oxidation requires a
second auxiliary enzyme in
addition to enoyl-CoA
isomerase: NADPH-
dependent 2,4-dienoyl-CoA
reductase. The combined
action of these two
enzymes converts a trans-
∆2,cis-∆4-dienoyl-CoA
intermediate to the trans-
∆2-enoyl-CoA substrate
necessary for ß oxidation
13. Oxidation of propionyl-CoA
produced by ß oxidation of
odd-number fatty acids.
The sequence involves the
carboxylation of propionyl-CoA
to D-methylmalonyl-CoA and
conversion of the latter to
succinyl-CoA. This conversion
requires epimerization of D- to
L-methylmalonyl-CoA, followed
by a remarkable reaction in
which substituents on adjacent
carbon atoms exchange
position
14. Comparison of ß-oxidation in mitochondria
and in peroxisomes and glyoxysomes.
■ The peroxisomal/glyoxysomal system differs from the mitochondrial
system in two respects:
(1) in the first oxidative step electrons pass directly to 𝑂2 , generating 𝐻2 𝑂2
and
(2) the NADH formed in the second oxidative step cannot be reoxidized in the
peroxisome or glyoxysome, so reducing equivalents are exported to the cytosol,
eventually entering mitochondria. The acetyl CoA produced by peroxisomes
and glyoxysomes is also exported; the acetate from glyoxysomes (organelles
found only in germinating seeds) serves as a biosynthetic precursor . Acetyl-
CoA produced in mitochondria is further oxidized in the citric acid cycle
17. Oxidation of fatty acids is a major
energy source in many organisms
■ About one-third of our energy needs comes from dietary triacylglycerols
■ About 80% of energy needs of mammalian heart and liver are met by
oxidation of fatty acids
■ Many hibernating animals, such as grizzly bears, rely almost exclusively on
fats as their source of energy
■ Some animals (camels) store fat as an eventual source of water
18. Fats provide efficient fuel storage
■ The advantage of fats over polysaccharides:
– Fatty acids carry more energy per carbon because they are more
reduced
– Fatty acids carry less water along because they are nonpolar
■ Glucose and glycogen are for short-term energy needs, quick delivery
■ Fats are for long-term (months) energy needs, good storage, slow
delivery
19.
20. Fat Bears Carry Out ß
Oxidation in Their Sleep
Many animals depend on fat
stores for energy during
hibernation, during migratory
periods, and in other situations
involving radical metabolic
adjustments.
