The Coffee Bean & Tea Leaf(CBTL), Business strategy case study
Lipids
1. Introduction
Definition: water insoluble compounds
Most lipids are fatty acids or ester of fatty acid
They are soluble in non-polar solvents such as petroleum ether,
benzene, chloroform
Functions
Energy storage
Structure of cell membranes
Thermal blanket and cushion
Precursors of hormones (steroids and prostaglandins)
Types:
Fatty acids
Neutral lipids
Phospholipids and other lipids
2. Classification:
Saponifiable—can be hydrolyzed by
NaOH to make soap
Non-saponifiable—cannot be
hydrolyzed, includes sterols such as
cholesterol
Saponifiable lipids are further subdivided:
Simple- made of fatty acids plus
alcohol
Compound- either phospho- or
glyco- lipids, which contain phosphate or
sugar groups as well as fatty acids
3. Lipids are non-polar (hydrophobic) compounds, soluble in organic solvents.
Most membrane lipids are amphipathic, having a non-polar end and a polar end.
Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end.
-
A 16-C fatty acid: CH3(CH2)14 COO
Non-polar
-
polar
A 16-C fatty acid with one cis double bond between
represented as 16:1 cis ∆ 9.
C atoms 9-10 may be
4.
5. Double bonds in fatty acids
usually have the cis configuration.
Most naturally occurring fatty
acids have an even number of
carbon atoms.
γ
4
β
3
α
2
O
C
1
O−
fatty acid with a cis-∆9
double bond
Some fatty acids and their common names:
14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid;
18:1 cis∆9 oleic acid
18:2 cis∆9,12 linoleic acid
18:3 cis∆9,12,15 α-linonenic acid
20:4 cis∆5,8,11,14 arachidonic acid
20:5 cis∆5,8,11,14,17 eicosapentaenoic acid (an omega-3)
6.
7. γ
4
β
3
α
2
O
C
1
O−
fatty acid with a cis-∆9
double bond
There is free rotation about C-C bonds in the fatty acid
hydrocarbon, except where there is a double bond.
Each cis double bond causes a kink in the chain.
Rotation about other C-C bonds would permit a more
linear structure than shown, but there would be a kink.
8.
9. Fats & Oils
Simplest lipids, called triacylglycerols or
simply triglycerides. Main form of fat
storage in plants, animals, and man.
Males store 21% fat on average, females
26%.
10. Essential Fatty
Acids
Fatty acids which cannot be made by the body, but are
important for health and growth are called essential.
Linolenic acid, found mostly in vegetable oils, is an
important reducer of LDL (low density lipoproteins),
which help to take cholesterol into the blood and
cause atherosclerosis (buildup of plaque in the blood
vessels) a prime cause of heart attacks
Arachidonic acid is important in making eicosanoids,
molecules which regulate and protect the body from
invasion by microorganisms.
11. Simple Lipids—Fatty Acids
Simple triglycerides contain the same fatty
acid in all three positions; mixed
triglycerides contain two or three different
fatty acids
Fatty acids are carboxylic acids with from 4 to
20 carbons in the chain. The chain can be
saturated (only single bonds) or
unsaturated (one or more double bonds in
the chain), Saturated are usually solid at
room temperature, unsaturated are usually
liquid
12.
13. Less common fatty acids
H3 C
iso – isobutyric acid
anteiso
R
H3 C
R
H3C
CH3
odd carbon fatty acid – propionic acid
hydroxy fatty acids – ricinoleic acid,
dihydroxystearic acid, cerebronic acid
cyclic fatty acids – hydnocarpic, chaulmoogric
(CH2)12-CO2H
(CH2)10-CO2H
acid
chaulmoogric acid
hydnocarpic acid
14. H3C
COOH
CH3
CH3
CH3
CH3
PHYTANIC ACID
A plant derived fatty acid with 16 carbons and branches at C 3, C7, C11 and
C15. Present in dairy products and ruminant fats.
A peroxisome responsible for the metabolism of phytanic acid is defective
in some individuals. This leads to a disease called Refsum’s disease
Refsum’s disease is characterized by peripheral polyneuropathy, cerebellar
ataxia and retinitis pigmentosa
15. Less common fatty acids
H3C
(CH2)10 C
C
(CH2)4 COOH
TARIRIC ACID
H2C
CH
(CH2)4 C
C
C
C
(CH2)7 COOH
ERYTHROGENIC ACID
These are alkyne fatty acids
16. Unsaturated fatty acids
number and position of the double
bond(s)Various conventions are in use for
indicating the
18
H3C (CH2)7
H
C
1
9
CH(CH2)7COOH
10
9
18:1,9 or ∆ 18:1
ω
H3C
n
2 3 4
5 6 7 8 9
10
CH2CH2CH2CH2CH2CH2CH2CH
17
ω
9, C18:1 or n-9, 18:1
18
CH(CH2)7COOH
10
9
1
19. Unsaturated fatty acids
Pentaenoic acid (5 double bonds)
20:5; 5,8,11,14,17 ω3: timnodonic acid or EPA
(all-cis-5,8,11,14,17-eicosapentaenoic acid)*
Hexaenoic acid (6 double bonds)
22:6; 4,7,10,13,16,19 ω3: cervonic acid or DHA
(all-cis-4,7,10,13,16,19-docosahexaenoic acid)*
Both FAs are found in cold water fish oils
20. Waxes
Waxes are simple lipids which are esters of long chain
alcohols and fatty acids. Beeswax is a 30 C alcohol
connected to a 16 C fatty acid
Waxes are completely water resistant and make the
coatings on leaves, skin, feathers, fur, and fruit. They
can be used on floors and furniture for the same
protecting quality.
24. Glycerol phospholipids
O
O
O
O
R
CH2 O O
O
HC
CH2 O
R
R
P
OH
CH2 O O
O
HC
CH2 O
OH
O
O
R
CH2 O O
O
HC
CH2 O
O
CH3
+
N
CH2
P
OH
H3C
R
CH2
CH3
R
OH
NH2
CH2
P
O
CH2
25. O
O
R
CH2 O O
R
O
HC
CH2 O
CH2
P
O
OH
Phosphotidyl serine
NH2
HC
COOH
O
O
R
CH2 O O
R
O
HC
CH2 O
HO
P
O
OH
CH
OH
CH
Phosphotidyl Inositol
CH
CH
CH
CH
HO
OH
OH
O
O
R
CH 2 O O
R
O
HC
HC
P
CH 2 O
HO
OH
OH
O
Phosphatidyl glycerol
CH2
HC
OH
O
O
O
R
R
CH2 O O
O
HC
CH2 O
O
OH
R
HC
P
OH
O
CH2
HC
OH
O O
CH
P
O
CH2
O
HO
Diphosphatidylglycerol (cardiolipin)
CH2
O
R
28. Ether glycerophospholipids
Possess an ether linkage instead of an acyl
group at the C-1 position of glycerol
PAF ( platelet activating factor)
A potent mediator in inflammation, allergic response
and in shock (also responsible for asthma-like
symptom
The ether linkage is stable in either acid or base
Plasmalogens: cis α,β-unsaturated ethers
The alpha/beta unsaturated ether can be hydrolyzed more easily
30. Phospholipase A1
Phospholipase A2
O
O
CH2 O
R
O
HC
CH2 O
O
P
OH
R
O
X
Phospholipase C
Phospholipase D
SURFACTANT ( DIPALMITOYL PHOSPHATIDYL CHOLINE
O
O
CH2 O
PALMITIC
O
HC
CH2 O
O
P
OH
PALMITIC
H3C
N
CH2
O
CH3
+
CH2
CH3
31. SPHINGOLIPIDS
H 3C
SPHINGOMYELIN
CH2
CH2
CH2
CH2
CH2
CH2
CH2 O
CH2
CH2
CH2
CH2
CH2
CH2
CH2
C
Palmitic acid
HO
+
Hydrophobic end
1
CH2
R
CH2
CH2
NH2
H3C
CH2
CH2
CH2
CH2
CH2
CH2
CH
CH
OH
CH2
CH2
CH2
CH2
CH2
CH2
CH
CH
CH2
Sphingosine
OH
O
C
NH
R
CH
CH
HC
CH
O
CH2
O
CH2
P
OH
CH3
OH
+
CH2
N
O
CH3
CH3
CERAMIDE
Hydrophilic end
SPHINGOLIPIDS
H3C
CH2
CH2
CH2
CH2
CH2
CH2
CH2 O
CH2
CH2
CH2
CH2
CH2
CH2
CH2
C
NH
H3C
CH2
CH2
CH2
CH2
CH2
CH2
CH
CH
OH
CH2
CH2
CH2
CH2
CH2
CH2
CH
CH
CH2
Ceramide
Acylated Sphingosine
O
HO
Palmitic acid
+
NH2
OH
Sphingosine
OH
OH
O
NH
R
1
OH
CH2
CH2 O
CH2
C
Ceramide
OH
Acylated Sphingosine
NH
R
CH
CH
HC
OH
CH
CH2
OH
Ceramide
R
O
1
NH
R
OH
OH
Ceramide
37. THE
UNIVERSAL
BLOOD
GROUP
ANTIGENS
ARE
SPHINGOLIPIDS WHICH ARE EXPRESSED ON THE SURFACE
OF ERYTHROCYTES
Fuc(a1-2)
Gal(B1-4)GalNAc(B) O
Cer
GalNAc(a1-3)
Blood Group A
Fuc(a1-2)
Gal(B1-4)GalNAc(B) O
Cer
Gal(a1-3)
Blood Group B
Fuc(a1-2)
Gal(B1-4)GalNAc(B) O
Blood Group O
Cer
40. Cholesterol, an
important constituent of cell
membranes, has a rigid ring
system and a short branched
hydrocarbon tail.
HO
Cholesterol
Cholesterol is largely
hydrophobic.
But it has one polar group,
a hydroxyl, making it
amphipathic.
PDB 1N83
cholesterol
41. HO
Cholesterol
Cholesterol
in membrane
Cholesterol inserts into bilayer membranes with its
hydroxyl group oriented toward the aqueous phase &
its hydrophobic ring system adjacent to fatty
acid chains of phospholipids.
The OH group of cholesterol forms hydrogen bonds
with polar phospholipid head groups.
42. Interaction with the relatively rigid cholesterol decreases the
mobility of hydrocarbon tails of phospholipids.
Cholesterol
in membrane
But the presence of cholesterol in a phospholipid membrane interferes with close
packing of fatty acid tails in the crystalline state, and thus inhibits transition to the
crystal state.
Phospholipid membranes with a high concentration of cholesterol have a fluidity
intermediate between the liquid crystal and crystal states.
47. peripheral
Membrane proteins may
be classified as:
peripheral
integral
having a lipid anchor
lipid
anchor
lipid bilayer
integral
Membrane
Proteins
Peripheral proteins are on the membrane surface.
They are water-soluble, with mostly hydrophilic surfaces.
Often peripheral proteins can be dislodged by conditions
that disrupt ionic & H-bond interactions, e.g.,
extraction with solutions containing high concentrations
of salts, change of pH, and/or chelators that bind
divalent cations.
51. lipid
anchor
membrane
cysteine
residue
palmitate
Some proteins bind to membranes via a covalently
attached lipid anchor, that inserts into the bilayer.
A protein may link to the cytosolic surface of the plasma
membrane via a covalently attached fatty acid (e.g.,
palmitate or myristate) or an isoprenoid group.
Palmitate is usually attached via an ester linkage to the
thiol of a cysteine residue.
A protein may be released from plasma membrane to
cytosol via depalmitoylation, hydrolysis of the ester link.
57. Glycosylphosphatidylinositols (GPI) are complex
glycolipids that attach some proteins to the outer surface
of the plasma membrane.
The linkage is similar to the following, although the
oligosaccharide composition may vary:
protein (C-term.) - phosphoethanolamine – mannose - mannose mannose - N-acetylglucosamine – inositol (of PI in membrane)
The protein is tethered some distance out from the
membrane surface by the long oligosaccharide chain.
GPI-linked proteins may be released from the outer
cell surface by phospholipases.
58. Lipid storage diseases
also known as sphingolipidoses
genetically acquired
due to the deficiency or absence of a catabolic enzyme
examples:
Tay Sachs disease
Gaucher’s disease
Niemann-Pick disease
Fabry’s disease
http://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid
59. What are Lipid Storage Diseases?
Lipid storage diseases are a group of inherited metabolic disorders in
which harmful amounts of fatty materials (called lipids) accumulate in
some of the body’s cells and tissues. Over time, this excessive storage of
fats can cause permanent cellular and tissue damage, particularly in the
brain, peripheral nervous system, liver, spleen, and bone marrow. Lipid
storage diseases are inherited from one or both parents who carry a
defective gene. Symptoms may appear early in life or develop in the
teen or even adult years. Neurological complications of the lipid storage
diseases may include ataxia, eye paralysis, brain degeneration, seizures,
learning problems, spasticity, feeding and swallowing difficulties, slurred
speech, loss of muscle tone, hypersensitivity to touch, burning pain in
the arms and legs, and clouding of the cornea
60. Genetic defects in
ganglioside metabolism
leads to a buildup of gangliosides
(ganglioside GM2) in nerve cells, killing them
enzyme that hydrolyzes here (beta hexosaminodase)
is absent in Tay-Sachs disease
Gal
NAc Gal Gal Glu
NAcNeu
CER
61. Tay-Sachs disease
a fatal disease which is due to the deficiency of
hexosaminidase A activity
accumulation of ganglioside GM2 in the brain of
infants
mental retardation, blindness, inability to
swallow
a “cherry red “ spot develops on the macula
(back of the the eyes)
Tay-Sachs children usually die by age 5 and often
sooner
62. Genetic defects in
globoside metabolism
Fabry’s disease:
Accumulation of ceramide trihexoside in kidneys of
patients who are deficient in lysosomal αgalactosidase A sometimes referred to as ceramide
trihexosidase
Skin rash, kidney failure, pains in the lower
extremities
Now treated with enzyme replacement therapy:
agalsidase beta (Fabrazyme)
63. Genetic defects in
cerebroside metabolism
Krabbe’s disease:
Also known as globoid leukodystrophy
Increased amount of galactocerebroside in the white matter of the
brain
Caused by a deficiency in the lysosomal enzyme galactocerebrosidase
Gaucher’s disease:
Caused by a deficiency of lysosomal glucocerebrosidase
Increase content of glucocerebroside in the spleen and liver
Erosion of long bones and pelvis
Enzyme replacement therapy is available for the Type I disease
(Imiglucerase or Cerezyme)
Also miglustat (Zavesca) – an oral drug which inhibits the enzyme
glucosylceramide synthase, an essential enzyme for the synthesis of
most glycosphingolipids
65. Genetic defects in
ganglioside metabolism
Metachromatic leukodystrophy
accumulation of sulfogalactocerebroside (sulfatide) in the
central nervous system of patient having a deficiency of a
specific sulfatase
mental retardation, nerves stain yellowish-brown with cresyl
violet dye (metachromasia)
Generalized gangliosidosis
accumulation of ganglioside GM1
deficiency of GM1 ganglioside: β-galactosidase
mental retardation, liver enlargement, skeletal involvement
66. Niemann-Pick disease
principal storage substance: sphingomyelin
which accumulates in reticuloendothelial cells
enzyme deficiency: sphingomyelinase
liver and spleen enlargement, mental
retardation
67.
68. Prostaglandins and other
eicosanoids (prostanoids)
local hormones, unstable, key mediators of
inflammation
derivatives of prostanoic acid
9
8
COOH
20
11 12
15
prostanoic acid
71. O
O
O
R
O
OO
O
P
X
H20
phospholipase A2 (enzyme that hydrolyzes
at the sn-2 position - inhibited
indirectly by corticosteroids)
O
COOH
CH3
COX is inhibibited by
aspirin and other NSAIDs
very unstable
bond
prostaglandin synthase
(also known as cyclooxygenase)
O
COOH
O
PGH2
OH
74. Prostacyclins, thromboxanes
and leukotrienes
PGH2 in platelets is converted to thromboxane A2
(TXA2) a vasoconstrictor which also promotes
platelet aggregation
PGH2 in vascular endothelial cells is converted to
PGI2, a vasodilator which inhibits platelet
aggregation
Aspirin’s irreversible inhibition of platelet COX
leads to its anticoagulant effect
75. Functions of eicosanoids
Prostaglandins – particularly PGE1 – block gastric
production and thus are gastric protection
agents
Misoprostol (Cytotec) is a stable PGE1 analog that
is used to prevent ulceration by long term NSAID
treatment
PGE1 also has vasodilator effects
Alprostadil (PGE1) – used to treat infants with
congenital heart defects
Also used in impotance (Muse)
76. Functions of eicosanoids
PGF2α – causes constriction of the uterus
Carboprost; “Hebamate” (15-Me-PGF2α) – induces
abortions
PGE2 is applied locally to help induce labor at
term
77. Leukotrienes
Non-peptidoleuktrienes: LTA4 is formed by dehydration of
5-HPETE, and LTB4 by hydrolysis of the epoxide of LTA4
O
COOH
C5H11
HO
COOH
LEUKOTRIENE A4 (LTA4)
C5H11
OH
LEKOTRIENE B4 (LTB4)
78.
79. Biological activities of
leukotrienes
1. LTB4
2. LTC4
3. LTD4
4. LTE4
- potent chemoattractent
- mediator of hyperalgesia
- growth factor for keratinocytes
- constricts lung smooth muscle
- promotes capillary leakage
1000 X histamine
- constricts smooth muscle; lung
- airway hyperactivity
- vasoconstriction
- 1000 x less potent than LTD4
(except in asthmatics)
80. Leukotrienes
Leukotrienes are derived from arachidonic acid via the enzyme
5-lipoxygenase which converts arachidonic acid to 5-HPETE
(5-hydroperoxyeicosatetranoic acid) and subsequently by
dehydration to LTA4
OH
OH
COOH
COOH
H
C5H11
H
S
Cys
gGlu
LEUKOTRIENE F4 (LTF4)
peptidoleukotrienes
C5H11
S
Cys
Gly
gGlu
LEUKOTRIENE C4 (LTC4)
81. Leukotrienes
Leukotrienes are synthesized in neutrophils, monocytes, macrophages,
mast cells and keratinocytes. Also in lung, spleen, brain and heart.
A mixture of LTC4, LTD4 and LTE4 was previously known as the
slow-reacting substance of anaphylaxis
OH
OH
COOH
COOH
H
C5H11
H
S
Cys
LEUKOTRIENE E4 (LTE4)
peptidoleukotrienes
C5H11
S
Cys
Gly
LEUKOTRIENE D4 (LTD4)