Structures and
properties of Lipids
From the lecture of Franck Fieschi
See - chapter 9 of the Biochemistry book (Voet, Voet, Pratt)
- http://www.lipidlibrary.co.uk/
[email protected]; [email protected]
The cell: the structural unit of living organisms
The cell = restricted area ….
but not hermetically closed!
The plasma membrane must
allow two opposed
objectives:
To isolate the cell
protection from the extracellular environment
preservation of the internal components
compartmentalization of (incompatible) functions
To establish contacts
sensing the external changes and
adaptation to these changes
acquisition of nutriments
reproduction
Composition of biomembranes
Percentage (in mass)
Membrane
Proteins
Lipids
Carbohydrates
Myelin
18
79
3
Red blood cell plasma mbn
49
43
8
Beef retina rods
51
49
0
Mitochondrium external mbn
52
48
0
Amoeba plasma mbn
54
42
4
Sarcoplasmic mbn
67
33
0
Chloroplast lamellae
70
30
0
Gram + Bacteria
75
25
0
Mitochondrium internal mbn
76
24
0
Source : Adapted from Guidotti, Annu. Rev. Biochem. (1972) 41 :731
- Biomembranes: lipids AND also proteins and carbohydrates
- Huge differences in the ratio lipids/proteins
(cf myelin versus mitochondrium internal mbn)
Lipids: Definition
Lipid: from the greek “lipos” = fat
Polar Hydrophilic
head
Apolar tail
Amphiphilic molecules
• simple molecules → small size
Hydrophobic
(< 5,000 g/mol, are not polymeric!)
• contain a significant proportion of
hydrocarbon chains (CH, CH2, CH3)
• → auto-association of these hydrophobic regions
(hydrophobic effect + Van der Waals interactions)
Many functions:
- “fat”: energy store and supply, thermic isolation
- Formation of biomembranes
- Intra- and intercellular signaling
Fatty acids: the building blocks
Fatty acids = weak carboxylic acids (neg. charge at physiological pH)
with long chain hydrocarbon side groups (≥ 12 C)
Saturated (reduced)
(Poly) unsaturated:
double bonds
flexible: free rotation around
each C-C bond
9 carbons
C 16:0
Alternative nomenclatures: None
Nomenclatures:
C 18:1 n-9
C 18:1 w-9
9 carbons
or
C 18:19
C 18:1 D9
(from the methyl terminal end) (from the carboxyl)
Fatty acids important in biology
Suffixes: saturated: “tic”, unsat.: “eic”, conjugated double bonds: “enic”
cis configuration
of most of the double bonds
30°rigid bend
in the hydrocarbon chain
→ Increase of membrane
fluidity
(less VDW interactions)
Double bonds at every third carbon: ω-3, ω-6, ω-9
→ 4 bonds: cyclization of the molecule
Lipid classification
Esterified fatty acids
Phospholipids
• Acylglycerols
• Waxes
• Glycerolipids
• Sphingolipids
Steroids
Glycolipids
• Glycoglycerolipids
• Glycosphingolipids
• Cholesterol
and derivatives
Fatty acid esters
-
complexity
+
Tristearyl glycerol
Stearic acid
(= triglyceride)
Stearic acid
+
Stearic acid
O
Ester: -C-O-R
3 H2O
3 esterifications
Waxes
Esterified
fatty acids
Phospholipids
Glycolipids
Steroids
Result from the esterification
of a long chain fatty acid
by a long chain alcohol
Minimal polar head: water insoluble, uncharged molecules
Protection against water:
- bird feathers,
- insect cuticle (See Animal Biology: Locusta)
- bee wax,
- human earwax
- plant wax (leaves, fruits)
Acylglycerols: synthesis by condensation
Esterified
fatty acids
Phospholipids
Glycolipids
Steroids
• Acylglycerol
Depending on the number of fatty acids:
1 - monoacyl glycerol
1, 2 - diacyl glycerol
1, 2, 3 - triacyl glycerol
3x
= belongs to
the triglycerides family
Non polar, water insoluble
Examples of triglycerides and nomenclature
Esterified
fatty acids
3
2
1
1,2,3 - Tristearyl glycerol
Phospholipids
Steroids
Glycolipids
3
2
1
1- palmitoleyl, 2 - stearyl, 3 - myristyl glycerol
Triglycerides: energy stores
Esterified
fatty acids
Phospholipids
Glycolipids
Steroids
Triglycerides
constitute the body fat
→ synthesized and stored
in fat globules
which occupy
the entire cytoplasm
of adipose cells
Fatty acids less oxydized than carbohydrates/proteins
→
yield more energy upon oxydation
Triglycerides: energy store
Esterified
fatty acids
Phospholipids
Glycolipids
Steroids
Ex of polar bears: triglycerides allow them to survive several months of starvation
Feed on calorie dense food (seal blubber)
for only a few weeks (when sea = frozen)
Subcutaneous storage of triglycerides
* long fasting period (summer-autumn)
without hibernation:
can last up to 8 months without eating,
just by burning their fat
(up to 1-1.5 kg of fat consumed/day)
→ no urine, no feces
→ water and carbon necessary to maintain their
life comes from the oxydation of triglycerides
* thermal insulation
Triglycerides: influence of the double bonds
Esterified
fatty acids
Phospholipids
Glycolipids
Saturated fat (in animal fat)
Steroids
Unsaturated fat (in vegetal fat)
Same number of C (18)
At room temperature
Solid: lowest energy conformation = extended Liquid: 30°rigid bend in the hydrocarbon chain
(cis-conformation of double bonds)
conformation → compaction of methylene groups
→ less compaction, more fluidity
Although the melting point (mp) of a triglyceride increases with the length
of its hydrocarbon chains, the presence of double bonds decreases the mp.
How to make solid margarine from liquid vegetal oil?
Esterified
fatty acids
To solidify
vegetal oil:
Phospholipids
Unsaturated
vegetal oil
H2, Ni2+
Hydrogenated
vegetable oil
problems: - partial hydrogenation
- trans hydrogenation
(risk of cardiovascular disease)
Emulsification
Glycolipids
Steroids
Phospholipids
Esterified
fatty
acids
• Glycerophospholipids
Phospholipids
Glycolipids
Steroids
• Sphingophospholipids
Carbonated skeleton = glycerol
→ esterified by:
- 2 fatty acids (hydrophobic tails),
- a variable polar residue
(hydrophilic head)
Glycerophospholipids: various polar heads
Esterified
fatty
acids
Phospholipids
Steroids
Glycolipids
PA
• Glycerophospholipids
Phosphatidic acid PA, anionic
Phosphatidyl Ethanolamine PE, neutral
(cephalins)
1 negative charge:
globally anionic or zwitterionic,
depending on the charge
of the variable polar head
Phosphatidyl Choline PC, neutral
(lecithins in egg yolk)
Variable polar head
Phosphatidyl Serine PS, anionic
Phosphatidyl Inositol PI, anionic
4-P PI
Phosphatidyl Inositol PI(4)P, anionic
(PI(3)P)
1,2 diacyl - glycérol 3- phosphate
Phosphatidyl Inositol 4,5-diP, PI(4,5)P2,
Anionic
4,5-P PI
Variable lipid composition in biomembranes
Esterified
fatty
acids
Phospholipids
Glycolipids
Steroids
PC, PE, Sphingomyelin and cholesterol are the lipids the most
abundant in biological membranes
Sphingolipids
Esterified
fatty
acids
Phospholipids
Glycolipids
Steroids
• Sphingophospholipids
• Glycerophospholipids
Named after the Sphinx because their function remained mysterious for a long time
Carbonated skeleton = sphingosine: C18 amino alcohol
CH3
2
CH2
Sphingosine
Trans configuration
of the double bond
Sphingolipids
Esterified
fatty
acids
Phospholipids
Steroids
Glycolipids
• Sphingophospholipids
choline
Sphingosine
Sphingomyelins (SM)
!
Addition of a fatty acid
by AMIDATION
Polar head substituted
by phosphocholine
(or phosphoethanolamine)
H
Ceramids: - N-acyl fatty acid derivatives of sphingosine
- Parent compounds of the most abundant sphingolipids
zwitterionic
Glycolipids
Esterified
fatty
acids
Phospholipids
Glycolipids
• Glycoglycerolipids
- Carbohydrate moiety attached to a phospholipid
on the exoplasmic surface of the biomembrane
- Plant chloroplasts (thylakoid membranes),
blue algae and a few photosynthetic
bacteria species: no phosphate
•Glycosphingolipids
External leaflet of the plasma membrane in
mammals and in the membranes of internal
organelles (ER, Golgi)
Steroids
Glycoglycerolipids: abundant lipids...
Esterified
fatty
acids
Glycolipids
Phospholipids
Steroids
Glycoglycerolipids
b1
b1
- Polar head:
1-10 sugar residues
(galactose/glucose)
linked in b1
- Uncharged: no phosphate
!!!
a1-6
Up to 80% of the total lipid content
of chloroplast membranes
Glycosphingolipids
Esterified
fatty
acids
Phospholipids
Glycolipids
H
Derive from ceramids
Cerebrosides
Addition of an uncharged polar head
= 1-6 sugar residues: * galactose
→ galactocerebrosides
* glucose
→ glucocerebrosides
Steroids
Gangliosides
Addition of a negatively charged polar head
= (ramified) oligosaccharide that includes at least
one sialic acid (N-AcetylNeuraminic Acid = NANA)
60 gangliosides identified to date
- Specific receptors for certain pituitary hormones
- receptors for bacterial toxins (cholera toxin)
Glycosphingolipids
Esterified
fatty
acids
Phospholipids
Glycolipids
Steroids
Recognition
of the
cholera toxin
Ganglioside
GM1
Ceramid: hooks
the lipid into
the membrane
Steroids
Esterified
fatty
acids
Cholesterol
21
Sterol specificities
12
Restricted hydrophilic part
(sterol)
2
3
1
A
4
11
9
10
5
B
6
13
22
20
18
19
Steroids
Glycolipids
Phospholipids
17
16
C 14 D 15
26
24
23
25
27
8
7
Extended hydrophobic part
Important rigidity
Possibility of esterification
by a fatty acid
- Derivative of cyclopentanoperhydrophenanthrene (4 fused, non planar rings)
- Present in the Vertebrate biological membranes (30-40 mol % of plasma membrane lipids)
- Metablolic precursor of numerous steroid hormones (which are not membrane lipids!)
Steroid hormones
Esterified
fatty
acids
Phospholipids
Steroids
Glycolipids
Classified according to the physiological responses they evoke
- Glucocorticoids (supradrenal glands: Cf BIO122, mouse):
reduce the inflammatory reaction
and increase the capacity to cope with stress
- Androgens and estrogens: sex hormones
Progesterone
Estradiol
Testosterone
Ex: Cortisone
Summary of the different classes of lipids
found in membranes
Esterified
fatty
acids
Glycolipids
Phospholipids
Steroids
• Glycerophospholipids • Glycoglycerolipids
•Glycosphingolipids
• Sphingolipids
• Cholesterol
Ionised polar head:
anionic / zwitterionic
gangliosides +
cerebrosides
glycoglycerolipids
MGDG DGDG
Uncharged polar head:
lack of phosphate
neutral
From lipids to membranes
Hydrophilic
polar heads
Hydrophobic
apolar tails
Scheme
Formula
Compact
model
Icon
water
Bilayer of phospholipids
water