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

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 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

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 Conti….
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 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

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 Conti…
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 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
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 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
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 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

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 Conti…
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 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

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 Activation fatty acid to Acyl CoA:
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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

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 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

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 Stages of Acyl CoA transport:
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 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)
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 Conti…
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 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

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 Conti…
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 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

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 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
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 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)

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 Conti…
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 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

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 ß-oxidation of Fatty Acids:
21

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 Conti…
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 Conti…
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 Oxidation of palmitoyl CoA:
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 Energetics of ß-oxidation:
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 ß-oxidation of odd chain fatty
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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?
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 Conti…
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 It is converted into succinyl CoA, which can the be

fed into the citric acid cycle to generate ATP

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 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
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 Conversion of D-isomer to L-isomer:
29

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 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

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 Conti…
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 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
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 Conti…
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 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
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 Conti…
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 Odd numbered double bonds handled by isomerase

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 ß-oxidation of polyunsaturated fatty
acids:
35

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