MUHAMMAD WAJID
Institute of Pharmacy Gulab Devi Educational
Complex, Lahore
Lipids Metabolism:
2
Lipids consist of Fatty acid and glycerol
Fatty acids consist of:
o A long chain hydrocarbon chain
o A carboxylic acid
Fatty acid have four important role:
o Fatty acids are used for fuel
o Fatty acids are used to build cell membrane (Phospholipids)
o Fatty acids are used to diversify protein functionality
o Fatty acids are used to build hormone and other messenger
molecule
Muhammad Wajid
Fatty acid metabolism:
3
Fatty acid metabolism consist of a breakdown
process and synthesis process
These two processes are essentially the reverse of
one another
Muhammad Wajid
Breakdown:
4
This is an oxidative process that releases an activated
acetyl CoA unit, and thereby shortening the
hydrocarbon chain by two carbon
The activated CoA can enter the citric acid cycle,
which can ultimately be used to form ATP molecule
Muhammad Wajid
Conti….
5
Muhammad Wajid
Synthesis:
6
This is a reductive process that builds up the
hydrocarbon chain of fatty acids
Beginning with an activated acyl unit and malonyl unit
the reverse process of fatty acid degradation are
followed in the opposite order
Muhammad Wajid
Conti…
7
Muhammad Wajid
Beta-Oxidation of Fatty acids:
8
Beta-Oxidation may be defined as the oxidation of
fatty acids on the beta-carbon atom
The alpha carbon (Cα) in organic molecules refers to
the first carbon atom that attaches to a functional
group such as a carbonyl
The second carbon atom is called the beta
carbon (Cβ), and the system continues naming in
alphabetical order with Greek letters
This results in the sequential removal of a two carbon
fragment, acetyl CoA
Muhammad Wajid
Stages of ß-oxidation:
9
Activation of fatty acids occurring in the cytosol
Transport of fatty acids into mitochondria
Beta-Oxidation proper in the mitochondrial matrix
Fatty acids are oxidized by most of the tissues in the body
Brain, erythrocytes and adrenal medulla cannot utilize
fatty acids for energy requirement
Muhammad Wajid
Fatty acid activation:
10
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
Muhammad Wajid
Conti…
11
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
Muhammad Wajid
Activation fatty acid to Acyl CoA:
12
Fatty acid
H2 H2
R C C COOH
ATP
Pyrophosphate
PPi 2Pi
O
H2 H2
R C C C AMP Acyladenylate
CoASH
AMP
O
H2 H2
R C C C CoA
AcylCoA
Muhammad Wajid
Transport of Acyl CoA into
mitochondria:
13
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
Muhammad Wajid
Stages of Acyl CoA transport:
14
It occur in four stages
Acyl group of acyl CoA is transferred to carnitine
catalyzed by carnitine acyltransferase I (CAT-I)
(present on the outer surface of inner mitochondrial
membrane)
The acyl-carnitine is transported across the membrane
to mitochondrial matrix by a specific carrier protein
(Translocase)
Muhammad Wajid
Conti…
15
Carnitine acyltransferase ll (CAT-II) (found on the
inner surface of inner mitochondrial membrane)
converts acyl-carnitine to acyl CoA
The carnitine released returns to cytosol for reuse by
translocase
Muhammad Wajid
Conti…
16
Muhammad Wajid
ß-oxidation proper:
17
Each cycle of β –oxidation, liberating a two carbon
unit-acetyl CoA, occurs in a sequence of four reactions
o Oxidation
o Hydration
o Oxidation
o Cleavage
Muhammad Wajid
Oxidation:
18
Acyl CoA undergoes dehydrogenation by an FAD-
dependent flavoenzyme, acyl CoA dehydrogenase
A double bond is formed between α & β carbons
(i.e., 2 & 3 carbons) 2
Hydration:
Enoyl CoA hydratase brings about the hydration of
the double bond to form β -hydroxyacyl CoA
Muhammad Wajid
Oxidation:
19
β-Hydroxyacyl CoA dehydrogenase catalyses the
second oxidation & generates NADH
The product formed is β-ketoacyl CoA
Cleavage:
The final reaction in β -oxidation is the liberation of
a 2 carbon fragment, acetyl CoA from acyl CoA
This occurs by a thiolytic cleavage catalysed by β-
ketoacyl CoA thiolase (or thiolase)
Muhammad Wajid
Conti…
20
The new acyl CoA, containing two carbons less than
the original, re-enters the β- oxidation cycle
The process continues till the fatty acid is completely
oxidized
Muhammad Wajid
ß-oxidation of Fatty Acids:
21
Muhammad Wajid
Conti…
22
Muhammad Wajid
Conti…
23
Muhammad Wajid
Oxidation of palmitoyl CoA:
24
Muhammad Wajid
Energetics of ß-oxidation:
25
Muhammad Wajid
ß-oxidation of odd chain fatty
26
acids:
Fatty acids with odd number of carbon atom are
oxidized in the same way that even number of fatty
acids except that one of the final product is three
carbon propionyl CoA molecule
So what is the ultimate fate of the propionyl CoA
molecule?
Muhammad Wajid
Conti…
27
It is converted into succinyl CoA, which can the be
fed into the citric acid cycle to generate ATP
Muhammad Wajid
Synthesis of D-Methyl malonyl CoA:
28
The propionyl CoA is converted into D-Methyl Malonyl
CoA by the activity of the enzyme propionyl Co
carboxylase
This enzyme depends on water soluble B-Vitamin biotin
This enzyme require carbon source, energy source and
biotin
Muhammad Wajid
Conversion of D-isomer to L-isomer:
29
Muhammad Wajid
Conversion of L-Methyl malonyl CoA
into Succinyl CoA:
30
This enzyme called methyl malonyl CoA mutase
catalyze an intra molecular rearrgement in which
the –co-S-CoA group migrates from C2 onto a
methyl group in exchange for a hydrogen
This rearrangement occurs only in the presence of
vitamin B12
Muhammad Wajid
Conti…
31
Muhammad Wajid
β-Oxidation of unsaturated fatty
acids:
32
The oxidation of unsaturated fatty acids require
additional enzymes that ultimately convert the fatty
acids into the intermediate that can be placed into
the β-oxidation pathway
Mono-saturated fatty acids:
Palmitoleate is a 16-carbon unsaturated fatty acid
that is activated in the cytoplasm and then
transported into the mitochondrion
It then undergoes three cycles of oxidation to form
∆3-enoyle CoA
Muhammad Wajid
Conti…
33
Acyl CoA dehydrogenase cannot act on Cis ∆3-Enoyl
CoA because of the double bond between 3rd and 4th
carbon
Another enzyme called Cis ∆3-Enoyl CoA isomerase
converts the Cis ∆3- to a trans ∆2- double bond
Now the trans ∆2- enoyl CoA can enter the β-
oxidation pathway and acted by the enoyl CoA
hydrates
Muhammad Wajid
Conti…
34
Odd numbered double bonds handled by isomerase
Muhammad Wajid
ß-oxidation of polyunsaturated fatty
acids:
35
Muhammad Wajid
36
Muhammad Wajid
