Activation of fatty acid, oxidation of fatty acid, beta oxidation, alpha oxidation, omega oxidation, activation of odd chain fatty acids, activation of unsaturated fatty acids, lipid metabolism

1. Lipid Metabolism
(activation of
fatty acid)
Anam Sharif
lecturer (University of Okara)

2. Definition:
lipids are biomolecules composed of long chain hydrocarbon,
chains formed mainly by ester linkage between alcohol and
fatty acids
A fatty acid contains a long hydrocarbon chain and a terminal
carboxylate group. The hydrocarbon chain may be saturated
(with no double bond) or may be unsaturated (containing
double bond).
Introduction: Lipids are fats which are essential for the
body and that required to perform some functions.
• Triglycerides and Cholesterol are the main lipids in the
living cell.
 Triglycerides acts as storage house of energy in
adipocytes and muscle cell
 Cholesterol is ubiquitous constituent of cell membrane,
steroids, bile acids and signaling molecule and produces
steroid hormones

3. Function of lipids and fatty acids:
1) They are the important sources of energy and they all
are most energy rich of all class of nutrients.
2) They form the structural components of cell membrane
and forms various messengers and signalling molecules
within the body.
3) Lipids function as a mechanical support for the vital
body organs.
4) Fatty acids are building blocks of phospholipids and
glycolipids.

4. Oxidation of fatty acids
 Oxidation of Fatty acids are an important source of energy
(adenosine triphosphate (ATP) for many cellular organisms.
 Excess fatty acids, glucose, and other nutrients can be stored
efficiently as fats and stored in tissues in the form of
triglycerides
 Triglycerides yield more than twice as much energy for the same
mass as do carbohydrates or proteins.
Types Of Fatty Acid Oxidation
Fatty acids can be oxidized by-
1) Beta oxidation- Major mechanism, occurs in the mitochondria
matrix. 2-C units are released as acetyl CoA per cycle.
2) Alpha oxidation- This Occurs in endoplasmic reticulum. Some
FA undergo α - oxidation in peroxisomes.one carbon is lost in the
form of CO2 per cycle.
3) Omega oxidation- Minor mechanism, but becomes important in
conditions of impaired beta oxidation. Its cellular site is
Endoplasmic reticulum

5. The proteins involved in cellular fatty acid uptake
include:
 Fatty acid translocase (FAT)
Translocase is general term for protein that assists in moving another
molecule, usually across a cell membrane.
 Plasma membrane-associated fatty acid-binding protein (FABPs)
The primary function of FABP is the facilitation of long-chain free
fatty-acid transport from the plasma membrane to intracellular sites for
oxidation (mitochondria, peroxisomes)
 Fatty acid transport proteins (FATPs)
Play role in the transport of exogenous fatty acids into the cell.
Sites for oxidation of fatty acids
• Mitochondria and peroxisomes are the sites for oxidation of
fatty acids
• Short- and medium-chain fatty acids are oxidized solely in mitochondria
• Long-chain fatty acids are oxidized both in mitochondria and
peroxisomes
• Very-long-chain fatty acids are oxidized in peroxisomes

6. Beta
Oxidation
of
Fatty Acid

7. 1. Beta-Oxidation
Beta-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.
Site of Beta oxidation
Structure of fatty acid
•The first carbon following the carboxyl
carbon is the alpha carbon.
•The second carbon following the carboxyl
carbon is the beta carbon.
•The last carbon in the chain, farthest from
the carboxyl group, is the omega carbon.

8. Beta oxidation of fatty acids
involves three stages
a. Activation of fatty acids in cytosol
b. Transport of fatty acids into mitochondria
c. Beta- oxidation in mitochondrial matrix.

9. a. Fatty acid
activation in
cytosol

10. 1. Fatty acid activation in
cytosol
 Fatty acid activation taking place in cytoplasm.
 Fatty acids are activated to acyl CoA by
thiokinases or acyl CoA synthetases.
 The reaction occurs in two steps & requires ATP,
coenzyme A and Mg2+
 Fatty acid reacts with ATP to form acyladenylate
which then combines with coenzyme A to
produce acyl CoA.
 Two high energy phosphates are utilized, since
ATP is converted to pyrophosphate (PPi).The
enzyme inorganic pyrophosphatase hydrolyses
PPi to phosphate.
 The immediate elimination of PPi makes this
reaction totally irreversible.

11. Thiokinase
 There are several thiokinases in human beings They
differ in substrate specificity and intracellular localization
 There are different thiokinases for short-, medium- and
long-chain fatty acids,
 thiokinase is present in mitochondria also But the
mitochondrial enzyme can act only on short-chain fatty
acids It cannot activate medium- and long-chain fatty
acids
 Thiokinases acting on medium- and long chain fatty acids
are present on:
i. Outer mitochondrial membrane
ii. Endoplasmic reticulum
 They convert long- and medium-chain fatty acids into
acyl CoA

12. b. Transport of Fatty
acid (Acyl Co) into
Mitochondria
 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.

13. Stages
It occur in four stages.
1.Acyl groups from acyl COA is transferred
to carnitine to form acyl carnitine catalyzed
by carnitine acyltransferase I, in the outer
mitochondrial membrane.
2. Acyl carnitine is then shuttled across the
inner mitochondrial membrane by a
translocase enzyme (specific carrier
protein).
3. The acyl group is transferred back to CoA
in matrix by carnitine acyl transferase II.
(found on the inner surface of inner
mitochondrial membrane)
4. Finally, carnitine is returned to the cytosol
for reuse by translocase.

14. c. Beta- oxidation
proper in
mitochondrial
matrix

15. Each cycle of β –oxidation, liberating a two carbon unit-acetyl CoA,
occurs in a sequence of four reactions
1. Oxidation
• The first reaction is the oxidation of acyl CoA by an acyl CoA
dehyrogenase to give α-β unsaturarted acyl CoA (enoyl CoA).
• FAD is the hydrogen acceptor.
• A double bond is formed between α & β carbons (i.e., 2 & 3 carbons)

16. 2. Hydration:
• The second reaction is the hydration of the double bond to β-
hydroxyacyl CoA (phydroxyacyl CoA).
• Enoyl CoA hydratase brings about the hydration of the double
bond to form β -hydroxyacyl CoA.

17. 3. Oxidation/Dehydration
• The third reaction is the oxidation of β- hydroxyacyl CoA to
produce β-Ketoacyl CoA NAD-dependent reaction.
• β-Hydroxyacyl CoA dehydrogenase catalyses the second
oxidation & generates NADH.
• The product formed is β-ketoacyl CoA.

18. 4. Cleavage
• The final reaction in β -oxidation is the liberation of a 2 carbon
fragment, acetyl CoA from acyl CoA by splitting the bond
between α and β carbons.
• This occurs by a thiolytic cleavage catalysed by β- ketoacyl
CoA thiolase (or thiolase).

19. Bioenergentics
of Beta
oxidation

20. • β-oxidation of palmitic acid will be repeated 7 cycles producing 8 molecules of
acetyl COA.
• In each cycle FADH2 and NADH+H+ is produced and will be transported to the
respiratory chain.

21. Oxidation of
odd chain
Fatty Acid

22. Oxidation of odd chain fatty acids is similar to that of even chain
fatty acids by the pathway of β-oxidation.
 Propionyl CoA is converted into succinyl CoA.
 Succinyl CoA is an intermediate in TCA cycle
 Propionyl CoA is gluconeogenic
Step 1:
• Propionyl CoA is carboxylated to D-methyl malonyl CoA by a
biotin dependent carboxylase. Biotin & ATP is utilized in this
step.
Step 2:
• Recemase acts upon D-methyl malonyl CoA to give L-methyl
malonyl CoA. This reaction is essential for the entry of this
compound into metabolic reactions of body.

23. Step 3:
• Mutase catalyzes the
conversion of L-methyl
malonyl CoA (a branched chain
compound) to succinyl CoA (a
straight chain compound).
• Mutase is an vitamin B12
dependent enzyme.
• Succinyl CoA enters the TCA
cycle, & converted into
oxaloacetate, it is used for
gluconeogenesis.

24. Oxidation Of
Unsaturated
Fatty Acids

25.  In the oxidation of unsaturated fatty acids, most
of the reactions are the same as those for
saturated fatty acids, only two additional
enzymes an isomerase and a reductase are
needed to degrade a wide range of unsaturated
fatty acids.
 Energy yield is less by the oxidation of
unsaturated fatty acids since they are less
reduced.
 Per double bonds 2 ATP are less formed, since
the first step of dehydrogenation to introduce
double bond is not required, as the double
already exists.

26.  Palmitoleoyl Co A undergoes three
cycles of degradation, which are
carried out by the same enzymes as
in the oxidation of saturated fatty
acids.
 The cis- Δ 3-enoyl CoA formed in
the third round is not a substrate for
acyl CoA dehydrogenase.
 An isomerase converts this double
bond into a trans- Δ 2 double bond.
 The subsequent reactions are those of
the saturated fatty acid oxidation
pathway, in which the trans- Δ 2-
enoyl CoA is a regular substrate .

27. α - Oxidation
of
Fatty Acids

28. • oxidation of fatty acid (methyl group at beta
carbon) with the removal of one carbon unit
adjacent to the α carbon from the carboxylic end
in the form of CO2
• Alpha oxidation occurs in those fatty acids that
have a methyl group(CH3) at the beta-carbon,
which blocks beta oxidation.
• No production of ATP
• This Occurs in endoplasmic reticulum.
• Some FA undergo α - oxidation in peroxisomes.
• Major dietary methylated fatty acid is phytanic
acid.
• It is derived from phytol present in chlorophyll,
milk & animal fats.


29. 1. Activation of phytanic acid
Phytanic acid is first activated to phytanoyl CoA.
2. Hydroxylation
Hydroxylation occurs at α-carbon atom.
Phytanoyl CoA is hydroxylated to 2-
hydroxyphytanoyl CoA.
3. Removal of formyl CoA( CO2)
Hydroxyphytanoyl CoA is cleaved into pristanal
and formyl CoA. Formyl CoA is broken down
into formate and eventually CO2
4. Oxidation of Pristanal
Pristanal is oxidized to pristanic acid.
5. Beta-oxidation of pristanic acid
Pristanic acid is activated to pristanoyl CoA,
which then undergoes b-oxidation. Six cycles of
b-oxidation produce isobutyryl CoA and three
molecules each of acetyl CoA and propionyl CoA

31. Omega
oxidation of
fatty acid

32. 3. Omega oxidation
• Oxidation occurs at (ω-omega) carbon—the
carbon most distant from the carboxyl group. Its
Cellular site is Endoplasmic reticulum
• It is a minor pathway but becomes active when
beta oxidation is defective.
• Omega oxidation is Catalyzed by hydroxylase
enzymes involving NADPH & cytochrome
P-450.
• Methyl (CH3) group is hydroxylated to CH2OH
& subsequently oxidized with the help of NAD+
to COOH group to produce dicarboxylic acids.
• When β-oxidation is defective & dicarboxylic
acids are excreted in urine causing dicarboxylic
aciduria.