Unit 4

Lipid

2
Course Outline
4. LIPIDS (15 hrs.)
1. − Structure and classification of lipids
2. − Biological membranes
3. − Digestion & absorption of lipids
4. − Metabolism of fatty acids:
• Biosynthesis and storage of fatty acids
• Oxidation of Fatty Acids
• Ketogenesis & Ketolysis
5. − Lipid transport and storage:
• Structure and function of Lipoproteins
6. − Cholesterol synthesis, transport, &
excretion
- References
❖Harper’s Biochemistry (Page No.111-122)
❖Pamela C.C. (Page No. 163-205)109
3
Objectives
After this lectures, you should be able to:
❑ Define lipids
❑ Classify lipids based on similarity and different
characteristics
❑ Describe metabolism of lipids
❑ Explain association of lipid diet with good
health

4
1.Classification &Structure of lipids

5
Classification &Structure of lipids
Definition
• Lipids (Gk→‘lipos’-fat) :
❖ heterogeneous groups of compounds
❖ fats, oils, steroids, waxes, and others
❖ more related by their physical than chemical properties
• Common physical properties of being:
❖ relatively insoluble in water
❖ soluble in none polar solvents : benzene, ether, chloroform

• Lipids are none polymeric unlike polysaccharides & nucleic acids

What are Functions of lipids????
6
 Cont.….
• Based on the chemical nature, lipids are classified as:

❖ Simple lipids:
o Esters of fatty acids (FA) with
alcohols
o Fats: fatty acids + glycerol (solid).

o Oils : fats in the liquid state

o Waxes: fatty acids + higher alcohols

7
Cont.….
• Based on the chemical nature, lipids are classified as:

❖ Compound lipids:
❑ Esters of FA with glycerol , & other group
❑ Phospholipids: FA+ alcohol + phosphate
o Glycerophospholipids
o Sphingophospholipids
❑ Glycolipid : Lipids+ carbohydrate moiety
o Cerebrosides
o Gangliosides
8
Cont.….
Precursor and Derived lipids:
• Compounds which are derived from lipids or
precursors of lipids

• Fatty acids: palmitic acid, linoleic acid, linolenic

acid, arachidonic acid

• Alcohols: glycerol, Vit D, Retinol, prostaglandins,

carotenoids

• Steroids: cholesterol
9
Cont.….

Complex lipids :
• Lipids complexed to other compounds
❖ Lipoproteins
❖ Proteolipids

10
Fatty acids (FA)
• An organic acids that occurs in natural triglycerides but do also
occur as free fatty acids, ranging in chain length of 4 - 36 carbon
atoms
• FAs are obtained from hydrolysis of fats/oils

• The chain may be classified into

❖Based on presence/absence of double bond
o Saturated : no double bonds

o Unsaturated: contain one or more double bonds

11
Cont.….

• Saturated fatty acids have single bond between the

carbons in the chain

• The most abundant saturated fatty acids: palmitic acid

(C16) & stearic acid (C18)

• Unsaturated fatty acids contain one or more double

bonds

12
Cont.….
❖ Mono unsaturated fatty acids (MUFA): presence
of only 1 double bond
✓ Oleic acid, C18, formula 18 : 1∆9

❖ Polyunsaturated fatty acids (PUFA): presence of

2 or more double bond
o Linoleic acid (C18 : 2 ∆9,12 )
o Linolenic acid (C18 : 3 ∆9,12,15)
o Arachidonic acid (C20 :4 ∆5,8,11,14 )

13
Cont.….
• Based on hydrocarbon chain
❖ Straight chain FA

o Even chain FA →4, 6,… carbon atoms ,e.g. butyric acid C-4
o Odd chain FA → 5, 7, carbon atoms, e.g. Valeric acid C-5

o Branched chain FA: e.g. phytanic acid C-20

14
Cont.….
• Based on length of the hydrocarbon chain:
❖ short chain fatty acids : 4-6

❖ medium chain fatty acids: 8-14

❖ long chain fatty acids : 16-24

❖ Very long chain fatty acids: 26-36

15
Cont.….
• Based on nutritional value
❖Essential fatty acids (EFAs)
• Fatty acids that the body cannot synthesize
and required good health

❖Only two fatty acids are known to be essential for

humans:
• α-linolenic acid (omega (ω)-3 fatty acid)
• Linoleic acid (ω- 6 fatty acid)
• Arachidonic acid essential if Linoleic acid is
deficient
What are biomedical importance of EFAs? 16
17
Eicosanoids
• Derived from eicosa (20-carbon) PUFA
❖ Prostanoids → prostaglandins (PGs),
prostacyclins (PGIs), & thromboxanes (TxB)
❖ Leukotrienes (LTs)
❖ Lipoxins (LXs)

18
19
Trans fatty acids (TFA)
• PUFA exist in cis configuration in naturally occurring
lipids
• TFAs present human milk, dairy products & in
hydrogenated edible oils
• Increase the shelf life of the fried food

• Fast food preparations have high TFA content

• Risk factors for chronic diseases: hyperlipidemia, insulin

resistance diabetes, adiposity

20
Cont.….

21
The Common Biological Fatty Acids

22
Nomenclature of Fatty Acids
Systemic naming
• “oic” being substituted for the final “e” in
the name of the hydrocarbon
➢ Saturated acids end in “anoic”

❖ e.g. octanoic acid

➢ Unsaturated acids with double bonds end in enoic

❖ e.g. octadecenoic acid

23
Cont.….
• Carbon atoms are numbered from the – COOH carbon
❖ C1, C2 (α-carbon)………….last carbon (ω)

• The number & positions of double bonds is indicated

24
Cont.….
Example
1. Oleic Acid ,C17H33 COOH
10 9
CH3 (CH2)7 –CH = CH (CH2)7 – COOH

C18 : 1 Δ9

2. Linoleic acid, C17H31 COOH

13 12 10 9
CH3 (CH2)4 –CH = CH-CH2-CH=CH-(CH2)7 – COOH
C18: 2Δ9,12
3. Ex. write systemic name for C17H29 COOH with 3 double bond at carbon 9,12 and 15? 25
26
Glycerol
• Commonly known as “glycerin”

• The simplest trihydric alcohol as it contains

three hydroxyl groups

• Colorless oily fluid with a sweetish taste

Glycerol
• Soluble in water & alcohol in all proportions
but insoluble in ether

27
Cont.….
Sources of Glycerol
• Endogenous source: lipolysis (main source) of fats
in adipose tissue

• Exogenous source: Dietary ,22 % glycerol directly

absorbed to portal blood from the gut.

Use of Glycerol
• Vasodilator (Nitroglycerine)
❖ treatment of cerebrovascular (CV) diseases
to reduces cerebral edema

• Nutritive value : converted to glucose & glycogen

28
Steroids
• Steroids are one of the most studied classes of
biological compounds in relation to fat

• Steroids contain a four-ring fused structure,

steroid nucleus
steroid nucleus
• 3 cyclohexane rings (A, B and C, phenanthrene
fused to cyclopentane ring (D)

• Cholesterol is probably the best known steroid

because of its association with atherosclerosis

29
Cont.….
• Cholesterol is the precursor of a large
number of important steroids

• Steroidal hormones, bile acids, vitamins D,

Cardiac glycosides, phytosterols & alkaloids

• Cholesterol is not very water soluble, it can

be converted to water-soluble bile salts

• What are functions of cholesterol?

• hydroxyl group on C3,
• double bond between C5 & C6
• 8 asymmetric carbon atoms on C 17
30
Triacylglycerols (TAG)
• Are esters of the trihydric alcohol glycerol
& 3FAs

• Rarely contain the same fatty acid at all

three positions → mixed TAG
❖ C 2 → Unsaturated FAs
❖ C1 → saturated FAs
❖ C3 → either of them

• TAGs coalesce within adipocytes to form

oily droplets, major energy reserve
31
Phospholipids
• Contains in addition to FAs & alcohol, other group
(phosphoric acid, nitrogenous base & other substituents)

• Two classes of phospholipids based on the alcohol:

❖ Glycerophospholipids

❖ Sphingophospholipids

32
Glycerophospholipids
• Basically similar to TAG except the 3rd carbon is
esterified to phosphoric acid

• It is known as phosphatidic acid or phosphatidate

• Phosphatidic acid is not a major membrane lipid (diacylglycerol 3-phosphate)

itself, but it forms the baseline structure for:

❖ Phosphatidylcholine (Lecithins)
❖ Phosphatidylethanolamine (Cephalins)
❖ Phosphatidylserine
❖ Phosphatidylinositol 4,5-bisphosphate (Inositides)
❖ Diphosphatidylglycerol (Cardiolipin) 33
Phosphatidylcholine (Lecithins)
• The most abundant PL of the cell membrane &
represent large amount store of choline

• Choline is used for synthesis of acetylcholine (NT)

• Dipalmitoyl lecithin is a major constituent of the

surfactant
Lecithin
• Lysolecithin is formed by removal of the FAs from (Phosphatidylcholine)

lecithin

• Hemolytic agent
34
Phosphatidylethanolamine (cephalin), &
Phosphatidylserine

• Found in most tissues and cell membranes

• Also found in large quantities in the myelin

sheath that surrounds nerve fibers

• Similar to lecithin except ethanolamine or

serine replaces choline

• Phosphatidylserine also plays a role in cell

signaling and apoptosis

35
Phosphatidylinositol (Inositides)
• Inositol is a cyclic hexahydroxy alcohol

• Similar structurally to lecithins/cephalins

except inositol as the base

• Major component of cell membrane PL

specifically at the inner leaflet

• Serve as second messengers during signal

transduction

36
Diphosphatidylglycerol (cardiolipin)
• Two phosphatidic acids esterified with their PO4-
groups to an additional glycerol molecule

• Found in mitochondria inner membrane & bacterial

wall

• Defect in cardiolipin cause mitochondrial dysfunction

• It is antigenic that could be recognized by antibodies

raised against Treponema pallidum

• Used in serological diagnosis of autoimmune diseases

37
Diphosphatidylglycerol (cardiolipin)

38
Sphingolipids
• Amino alcohol sphingosine
• Two classes:
─ Sphingomyelins
─ Glycolipids
• Ceramides:
↪ Precursors for phosphorylated &
glycosylated sphingolipids
• Ceramide = Sphingosine + FA
• 50% of our skin's composition
Ceramide
39
 sphingosine
Sphingomyelins
• Found in large amounts in brain &
nerves

• Yield a fatty acid, phosphoric acid,

choline, & sphingosine by hydrolysis Sphingomyelin

• Important constituent of the myelin of

nerve fibers

40
Glycolipids/Glycosphingolipids
• Derivatives of ceramides ,sugar is attached to -
OH group on C-1

• Essential components of the outer leaflet of the

plasma membrane, with greatest amounts in
nerve tissue

• Function as regulation of cellular interactions,

growth, development, antigenic determinant

41
Types of glycolipids

• Cerebrosides: single sugar linked to ceramide

❖ Galactocerebroside
❖ Glucocerebroside

• Globosides: two or more sugars linked to ceramide

• Usually D-glucose, D-galactose, or N-acetyl-D-

galactosamine

• Gangliosides: oligosaccharides and one or more residues of

N-acetylneuraminic acid
42
Cerebrosides:

Globosides 43
Gangliosides 44
2. Biological membranes

45
 Definition of membranes
• Bio-membranes are thin flexible surface separating
cells & compartments from their environments

46
Cont.….
Membranous organelles

Lysosome
Mitochondrion Golgi apparatus ER Nucleus

47
Cont.….
Fluid mosaic model

48
Cont.….
Components

Lipids

Proteins

Carbohydrate

49
Lipids
• A lipid bilayer is the basic structural element of membranes

• Major lipid biomembrane:

❖ Phospholipids
❖Glycolipids
❖Cholesterol

50
Cont.….
Phospholipids
❖Consists of :
❖Head
❖Polar group
❖Phosphate + alcohol
❖Tail
❖Non-polar
❖Fatty acids

51
Cont.….
Common phospholipids in membrane
• Phosphoglyceride
❖Phosphatidylcholine
❖Phosphatidylethanolamine
❖Phosphatidylinositol
❖Phosphatidylserine
• Sphingomyelin

52
Phosphoglyceride Sphingomyelin

Sphingosine

53
Cont.….

Snake venom
❖Snake is synthesized in modified salivary
glands of poison snake
❖Poisons snake venom contains phospholipase
which lyses phospholipids in RBC

54
Cont.….
• Common fatty acids in membrane
❖Palmitic (16 : 0)
❖Stearic (18 : 0)
❖Oleic (18 : 1)
❖Linoleic (18 : 2)
❖Arachidonic (20: 4)
❖Docosahexaenoic acid (22 : 4)

55
 Polar
(hydrophilic )
head

Nonpolar
(hydrophobic)
tails
S
S U
57
Cont.…

❖When phospholipids are mixed in water, they forms

microscopic lipid aggregates

❖ Micelles: hydrophobic regions aggregated in the interior

58
Cont.….
• Bilayer lipid:
❖ The basic structural element of
membranes
❖Two lipid monolayers form 2-D
or 3-D sheet
❖ Key structures in biological
membranes

59
60
Cont.….
• Liposomes:
❖ Spherical lipid bilayer membrane that
encloses a small amount of liquid
❖Are made in the laboratory
❖Are used as vehicles or drug delivery

61
Cont.….
• Cholesterol
❖ Cholesterol intercalates among the
phospholipids of the membrane
❖ Increases the mechanical strength of
the membranes
❖Reduces permeability to water and
small molecules

62
Cont.….
• Distribution of lipids in the membranes
❖ Outer leaflet
o Sphingomyelin
o Phosphatidylcholine
o Cholesterol
❖ Inner leaflet
o Phosphatidylserine
o Phosphatidylethanolamine
NB: Phosphatidylserine on outer membrane marks apoptosis
63
The distribution of lipids in the membranes of a typical cell

64
Membrane proteins
• Three types of membrane proteins differ in their
association with the membrane
❖Integral membrane proteins

❖Peripheral membrane proteins

❖ Amphitropic proteins

65
Cont.…
• Integral membrane proteins
❖Interact extensively with the
phospholipids
❖Requires the use of detergents for
their solubilization
❖Span bilayer as a bundle of α-helical
transmembrane segments
❖Are usually globular & amphipathic

66
Cont.…
• Peripheral proteins
❖do not interact directly with the
hydrophobic cores
❖do not require use of detergents for
their release
❖bound to the hydrophilic regions of
specific integral proteins
❖can be released by treatment with
salt solutions of high ionic strength

67
Cont.…

• Amphitropic proteins
❖ Found both in the cytosol and in
association with membranes.
❖Reversible association of amphitropic
proteins with the membrane is regulated
❖For example, phosphorylation or ligand
binding

68
• Function of membrane proteins

69
Carbohydrate
• Carbohydrates are present as oligosaccharides covalently
linked to lipid (glycolipid) or Protein (glycoprotein)
• They are attached on external side in cell membrane, but
in luminal surface of ER

• Cell to cell recognition

❖ Distinguishing features in human transfusion and
transplantation
❖ Allows immune cell to differentiate body cell or
foreign cells 70
Cont…
Types
• Glycoprotein =˃ protein + oligosaccharide
• Found exoplasmic face of plasma membrane
• Functions to increase protein solubility

• Glycolipid =˃ lipid + oligosaccharide

❖ Found exoplasmic of leaflet
❖ Oligosaccharide portion face outside
❖ Gangliosides in many nerve cell

71
Movement of molecules across membranes
• Membranes are
❖ permeable to hydrophobic substances
❖ barrier to hydrophilic substances
• Lipophilic substances can cross a lipid bilayer by simple
diffusion
• O2, CO2, NH3, ethanol

72
Cont…
• Charged or large molecules may cross a lipid bilayer only
with the help of transport protein
• Facilitated diffusion
❖ The proteins simply provides a means
❖ Molecules move down an electrochemical gradient
• Pore or channel: opening through which specific
molecules can move
❖ Na+ channels → Na+, K+, and Cl−
❖ Aquaporins → water-transporting
73
Cont…
• Carrier transport proteins
❖ bind a molecule on one side of a
membrane,
❖conformational change
❖release the molecule on the other side
of the membrane
• e.g. GLUT-type glucose transporters

74
Cont.…
• Active transport
❖ Move molecules against electrochemical gradient
❖ Use energy
❖ Are also called pumps
❖ E.g.
o Na+-coupled amino acid transporters
o Na+: K+- ATPase
o Na+-coupled glucose transporter (SGLT)

75
Cont…
Three types of transport proteins

76
3.Digestion & absorption of lipids

77
Lipids in diet
TAG , 95% Phospholipids
5%

Cholesteryl Ester (10-15%) Free Cholesteryl Ester (85-90%)

78
Cont.…

• Lingual & gastric lipases are produced in the

mouth & stomach respectively

• Preferentially, hydrolyze short-& medium-chain

Fatty Acids (≤ C-12)

• Cut bonds at C1 & 3

• Optimum pH of this lipase 4-6

• Products: Two fatty acids & 2-monoacylglycerol

79
Cont.…

• Lingual & gastric lipases are of little use in

the adult stomach (low pH)
• These enzymes are active in neonates due to:
❖ stomach pH nearer to neutrality
❖ diets contain mainly milk lipids

80
Cont.…

• In small intestine, difficult to digest hydrophobic

molecules in hydrophilic environment

• Emulsification

• Favored by:
₋ Bile salts (detergent action)
₋ Peristalsis (mechanical mixing)
₋ Phospholipids

81
Cont.…
Action of pancreatic enzymes

• Pancreatic Lipase hydrolyzes TAG at C-1 & 3 : free fatty

acids (FFAs) & 2- monoacylglycerols (MAG)

• Pancreatic lipase is activated by Ca++

82
Cont.…

83
Cholesteryl ester degradation
• Cholesteryl esters are hydrolyzed by pancreatic cholesteryl
ester hydrolase (cholesterol esterase)

• Cholesteryl ester hydrolase activity is greatly increased in

the presence of bile salts

• Products: cholesterol, free fatty acids ,Vit A,E

84
Phospholipid degradation
• Phospholipids (PL) is digested by pancreatic phospholipase
A2 that splits off fatty acid in C2 leaving lysophospholipid

• FA in the lysophospholipid is removed by lysophospholipase

leaving glycero-phospho-base

• Glycero-phospho-base is then,
➢ break to its components
➢ absorbed
➢ pass out with stools

85
Absorption of lipids by intestinal mucosal cells
Micelles formation
• Bile salts, free fatty acids, free cholesterol & 2-
monoacylglycerol form clusters of amphipathic lipids

• The monoglycerides and fatty acids free in solution are

absorbed, not in the micelles

• Monoglycerides, cholesterol & fatty acids can just diffuse

across the plasma membrane of the enterocyte

Note : no need micelles for short & medium chain fatty

acid absorption

86
87
Re-esterification Inside the Mucosal Cell
• Long chain fatty acids are re-esterified to form TAGs in intestinal
mucosal cell

• Fatty acids are activated to fatty acyl CoA ,and then 2 fatty
acyl CoA react with MAG to form TAG

• Chylomicrons →TAG, cholesterol ester, phospholipid,

apoproteins B48, and apo-A
→ transport content to liver

• SCFA and MCFA do not need of re-esterification

90
91
Fate of Chylomicrons
•Chylomicrons are taken up by adipose tissue, skeletal muscle
and liver

• Liver synthesizes endogenous TAGs, and are transported as

VLDL to adipose tissue

•TAGs in adipose tissue are hydrolyzed to produce free fatty

acids (FFA) in condition of starvation

• The remnants of chylomicrons with cholesterol & apolipoproteins,

travel in the blood to the liver where they are taken up by endocytosis
93
Summary of digestion & absorption of lipids

94
Inhibitors of lipid digestion and absorption
Orlistat:
• Non-hydrolysable analog of TAG & inhibitor of pancreatic lipase
• Blocks lipid absorption and hence results in lipid excretion

Olestra:
• Non-hydrolysable artificial fat produced by esterification of fatty acids
with sucrose instead glycerol

Ezetimibe:
• Blocks protein that mediates cholesterol transport across the
apical plasma membrane of enterocyte

95
Maldigestion and malabsorption of lipid: steatorrhea
• Steatorrhea is the loss of greater than six gram of fat, fat
soluble vitamins (A,D,E,K) & EFAs
Causes

• Defective digestion
❖ Deficiency of pancreatic lipase → chronic pancreatitis, cystic
fibrosis
❖ Fecal fat is mostly undigested TAGs

• Defective Absorption
❖ Deficiency of bile salts → bile duct obstruction as in tumors or
stones in bile duct
❖ Defective intestinal mucosal cells → surgically removed, coeliac
diseases
❖ Fecal fat is in the form of 2-monoacylglycerol 96
Possible causes of steatorrhea

97
4. Metabolism of fatty acids:
− Biosynthesis and storage of
fatty acids
− Oxidation of Fatty Acids
− Ketogenesis & Ketolysis

98
Biosynthesis and storage of fatty acids

99
Biosynthesis and storage of fatty acids
• Source of fatty acid for the body

Diet De novo synthesis

• Excess carbohydrate & proteins can be converted to

fatty acids

• Site:
❖ liver
❖ lactating mammary gland
❖ adipose issue
❖ kidney
100
Cont...
• Requirements :
❖ Acetyl CoA
❖ ATP
❖ Enzyme
o Fatty acid synthase
o Acetyl CoA carboxylase
❖ NADPH

101
Cont...
• Fatty acids synthesis involves condensation of 2 carbon units (acetyl
CoA), to form long hydrocarbon chain in a series of reaction

• The biosynthetic pathway occurs in 3 stages:

❖ Transport of acetyl CoA to cytosol

❖ Conversion of acetyl CoA to malonyl CoA

❖ Reactions’ of fatty acid synthase complex

102
 Transport of acetyl CoA to cytosol
• Acetyl-CoA is mainly found in mitochondria which cannot
pass out

• Intra-mitochondrial acetyl-CoA first reacts with OAA to

form citrate in the TCA cycle (citrate synthase)

• Citrate is transported out by a transporter protein in

exchange of malic acid

• An enzyme citrate lyase cleaves citrate into acetyl-CoA

& OAA in cytoplasm

Citrate + CoA + ATP → acetyl-CoA + oxaloacetate + ADP + Pi 103

104
Conversion of acetyl CoA to malonyl CoA
• The key reactions of fatty acid synthesis are the carbon to-
carbon condensations

• Acetyl CoA needs to be converted malonyl CoA (C-3)

• Carboxylation of acetyl CoA by acetyl CoA carboxylase

produces malonyl CoA

• The reaction utilize ATP and use biotin as carrier of COOH

• Rate-controlling steps in fatty acid synthesis

105
The acetyl-CoA carboxylase reaction
106
Reactions of fatty acid synthase complex
• Fatty acid synthase is composed of two identical
subunits, which each have seven catalytic activities

107
Domains of fatty acid synthase complex
1.Acetyl CoA – ACP transacylase.
2.Malonyl CoA- ACP transacylase.
3.β- Ketoacyl – ACP synthase.
4.β- Ketoacyl- ACP reductase.
5.β –Hydroxyacyl – ACP dehydratase.
6.Enoyl – ACP reductase.
7.Palmitoyl thioesterase

108
Cont...

• Fatty acid synthase prosthetic groups:

❖Thiol (-SH) group side-chain of keto acyl synthase
enzyme

❖Thiol (-SH) of phosphopantetheine component of Acyl carrier

protein (ACP)

❖Are closely aligned

109
Steps of Synthesis of fatty acid
1. An acetate is transferred from acetyl CoA to the –SH group of
the ACP : Acetyl CoA-ACP acetyltransacylase

2.Then, it is transferred to a temporary holding site, the thiol group

of a cysteine residue on the enzyme

3.Now, the vacant ACP accepts malonate (C-3) unit from malonyl
CoA: Malonyl CoA-ACP transacylase

4.Acetyl group on the cysteine residue condenses with the malonyl

on ACP , CO2 is released: 3-Ketoacyl-ACP synthase

110
Cont...
5. The keto group is reduced to an alcohol: 3-Ketoacyl- ACP
reductase.

6. A molecule of water is removed to introduce a double bond

between carbons 2 & 3: 3-Hydroxyacyl-ACP dehydratase.

7. The double bond is reduced : Enoyl-ACP reductase

111
 2. Temporary
holding site (-SH)

6.3-Hydroxyacyl-ACP
dehydratase

115
Enoyl-ACP
reductase

Repeat steps [2] – [7] six times more

Palmitate

116
Butyryl-ACP 117
 Overall reaction of palmitate synthesis

ACC
8 acetyl CoA + 14 NADPH + FAS Palmitic acid + 14NADP + +
14H + + 7 ATP 7 ADP + 7 Pi + 6H2O

119
Regulation of fatty acid synthesis
• Allosteric Modulation of ACC:
❖ Citrate
❖ malonyl CoA and palmitoyl-CoA ⊖
• Covalent mechanisms
❖ Epinephrine/ Glucagon ⊖
❖ Insulin ⊕
• Induction-repression of enzyme synthesis
❖ Prolonged consumption of high- carbohydrate or fat -
free diet leads to increased ACC synthesis
❖ High- fat diet or fasting leads to decreased ACC synthesis
120
 Fates of palmitate
Chain elongation Desaturation

121
• Chain elongation
❖Palmitate (16:0),the primary end product of fatty acid synthase it
can be further elongated

❖Elongation requires a system of separate enzymes, in ER &

mitochondria

❖Malonyl CoA is the two-carbon donor and NADPH supplies the

electrons

❖The brain has elongation capabilities to produce the very-long-

chain fatty acids

❖The more active elongation system of the ER forms stearoyl-CoA

122
Cont.…
• Desaturation
❖Desaturases typically inserts the first double bond
between C9 & C10 also present in the SER

❖Palmitate & stearate serve as precursors for palmitoleate,

16:1 (D9), and oleate, 18:1(D9), respectively

❖NADH, cytochrome b5 and its FAD-linked reductase

❖Humans have C 9, 6, 5 and 4 desaturases, but lack the

ability to introduce double bonds from C10 to the ω end

❖However, plants & bacteria can adds double bond at

both site 123
Electron transfer in the desaturation of fatty acids
124
Action of plant desaturase 125
Cont.…
• Synthesis of Eicosanoids

❖Eicosanoids are family of very potent signaling

molecules

❖Linoleate may be converted to arachidonate

(eicosatetraenoate)

❖ Arachidonate may be then converted to

prostaglandins

126
129
130
Cont.…

• Esterification
❖ Esterified with fatty acid or cholesterol to form
TAG or cholesteryl ester

• Others…..

131
Regulation of fatty acid synthesis
• Allosteric Modulation of ACC:
❖ Citrate
❖ malonyl CoA and palmitoyl-CoA ⊖
• Covalent mechanisms
❖ Epinephrine/ Glucagon ⊖
❖ Insulin ⊕
• Induction-repression of enzyme synthesis
❖ Prolonged consumption of high- carbohydrate or fat -
free diet leads to increased ACC synthesis
❖ High- fat diet or fasting leads to decreased ACC synthesis
132
Cont…

133