4. Fatty Acids - Physical
Properties
• Solubility
• Longer chains
• more hydrophobic, less soluble
• Double bonds increase solubility
• Melting points
• Depend on chain length and saturation
• Double bonds lead acyl chain disorder and
low melting temps
• Unsaturated FAs are solids at Room Temp
5.
6. Triacylglycerols
• Glycerol head
group HO-CH2-
CH(OH)-CH2-OH
• Ester linkage from
each hydroxyl to
Fatty acid
• Carboxylate
charge is lost
• TAGs more
hydrophobic than
FAs
7. Triacylglycerols in Energy
Storage & Thermal insulation
• Concentrated source of energy
– Energy derived from oxidation reactions
– More completely reduced state yields 2x the
energy/g as Carbohydrates
• Pure non-aqueous phase
– Lipases hydrolize the ester linkages to release
Fatty Acids
8. Triacylglycerols in food
• Vegetable Oils – unsaturated
- catalytic hydrogenation reduces
double bonds
- less specific than enzymatic
methods makes some trans-fats
9. Waxes
• Esters of long chain fatty Acids with long chain
alcohols
• Higher melting points
• Hydrophobic
10. 10.1 Summary
• Lipids are water insoluble
• Common Fatty Acids have 12-24 carbon
atoms (an even number)
• Triacyl glycerols primary storage fats in
food.
12. Glycerophospholipids
• Phosphorylation of
Glycerol creates a
stereocenter on C2
– L glycerol 3 phosphate
head group adds a
negative charge
– Phospho diesters with:
• Ethanolamine, Choline,
Serine, Glycerol, Inositol
Phosphate, Phosphatidyl
Glycerol
13.
14. 2 Fatty Acid chains esterified to
remaining hydroxyls (diacyl
glycerol)
• Common Glycerophospholipids have
– 16:0 or 18:0 at C1
– 18:1 (Δ 2
) or 20:1 (Δ 2
) at C2
15. Ether
Lipids
• Ether linkage instead
of ester at C1
• Plasmalogens have a
C1=C2 double bond
• Platelet activating
factor is a signalling
lipid with:
– saturated acyl chain at
CI (ether linkage)
– acetyl ester at C2
– phospho-choline on C3
16. Galactolipids and Sulfolipids
in Chloroplasts
• Galactose (or DiGal)
attached to Glycerol
C3
• Sulpho lipids contain
sulphonate on sugar
• Sulphonate charge
replaces typical
phosphate charge
17. Archael "Extremophile" Lipids
• Longer acyl chains and dual head groups can
can replace 2 normal phospholipids
– Replace a bilayer with a monolayer
• Ether linkages
• More stable at high temperatures, Acid
Environments
18. Sphingolipid
s
• Sphingosine is a combination
acyl chain & Head group
(HO-1
CH-CH=CH-(CH2)12-CH3
2
CH-NH3
3
CH2-OH
• Acyl chain in amide linkage at C2
makes a ceramide
19. Head groups at C3
• Sphingomyelins
– Phosphocholine or
Phosphoethanolamine
• Glycosphingolipids
– Cerebrosides have
Glucose, galactose
– Globosides have
simple neutral
Oligosaccharides,
– Gangliosides have
more complicated
anionic
oligosaccharides
21. Lipid Degradation in
Lysosomes
• Phospholipase A1 cleaves
ester linkage at C1
– glycerophospholipid =>
lysophospholipid + FA1
• Phospholipase A2 is a
lysophospholipase
– cleaves ester linkage at C2
– lysophospholipid =>
Glycerophosphate head group +
FA2
• Phospholipase C cleaves
phospho-glycerol ester linkages
– glycerophospholipid => diacyl
glyceral + phospho head group
22. Sterols
• Have 4 fused rings
• Cholesterol is the
major sterol in
vertebrates
• Steroid Hormones
– Testosterone,
Estrogen
23. 10.2 Summary
• Polar Lipids major constituent of membranes
• Glycerophospholipids are charged depending
on constituents
• Galactolipids are abundant in chloroplasts
• Archaebacteria have extreme lipids
• Sphingolipids are built on a sphingosine
framework
• Sterols have a polycyclic aromatic ring
structure
24. 10.3 Lipids as Signals,
Cofactors and Pigments
• Phosphatidylinositol signalling
• Sphinogosine
• Eicosanoids
• Steroid Hormones
• Plant signalling
• Vitamin A and D
• Vitamin E and K - Redox Cofactors
• Dolichols
25. Phosphatidylinositol signaling
• PI is phosphorylated to give PI 4,5
bisphosphate
• On the inner (cytoplasmic) leaflet of the cell
membrane
• Phospholipase C cleaves PI 4,5
bisphosphate to give
– IP3 and DAG
– both molecules active in signalling through protein
kinase C
• Pleckstrin homology domains bind to inositol
3,4,5 triP
27. Eicosanoids
• Are derived from Arachadonic Acid 20:4(Δ5,8,11,14
)
• NSAIDs (Aspirin and ibuprofin) block production of
Prostaglandiins and thromboxanes
• Prostaglandins - C8-C12 bond generates 5 membered ring. Stimulate
adenylyl cyclase
• Thromboxanes - C8 -C12 bond + Oxygen in heterocyclic ring
• Leukotrienes involved in asthma and other processes
28. Steroid Hormones
• low solubility in
water
• transported by
proteins,
• can pass through
membranes
29. Vitamin A and D
• Isoprene is a common
precursor for sterols,
Vitamin D and Vitamin A
– CH2=C(CH3)-CH=CH2
• D vitamins derived from
Sterols
30.
31. Vitamin E and K - Redox
Cofactors
• Vitamin E and other tocopherols are antioxidants
• Vitamin K is an isoprenoid blood Clotting cofactor
– Warfarin is a vitamin K derivative (named after the
Wisconsin Alumni Research Foundation WARF)
– rat poison that kills by inducing hemorrhage, internal
bleeding
– Can be used medically to inhibit clotting
• Dolichols
– Serve as membrane anchors for the assembly of
oligosaccharides by glycosyl transferases
32.
33. 10.3 Summary
• Minor lipids are essential cofactors
• PI bisP => inositol trisP + DAG
• Eicosanoid hormones from arachidonic acid
• Steroid Hormones
• Fat Soluble Vitamins
• Fat soluble quinones - electron transport
• Dolichols - membrane anchors for "solid
phase" oligosaccharide synthesis
34. 10.4 Working with
Lipids
• Lipid Extraction
• Adsorption Chromatography
• Gas Liquid Chromatography
• Specific Hydrolysis
• Mass Spectrometry
35. Lipid Extraction
• Lipid Definition: Any of a group of organic
compounds, including the fats, oils, waxes,
sterols, and triglycerides, that are insoluble in
water but soluble in nonpolar organic
solvents, are oily to the touch, and together
with carbohydrates and proteins constitute
the principal structural material of living cells.
- First step is an organic solvent extraction to
separate the lipids (by definition) from
everything else - Commonly Chloroform
Methanol Water Mixtures
36. Adsorption
Chromatograph
y
• Silica gel is insoluble
in and more polar
than CHCl3
• Polar lipids adsorb
from the solvent,
bind to the column
• Elution with
successively more
polar solvents eg.
Acetone then MeOH
37. Gas Liquid
Chromatography
• Good for analysis of
volatile components
• Fatty acids analysed as
Methyl esters after acid
or base hydrolysis in
MeOH
• Adsorption from gas
phase to the liquid
(instead of solid from
liquid) slows the passage
through the column
38. Specific Hydrolysis
• Acid or base hydrolysis is non-specific
• Enzymatic hydrolysis requires specific
interactions
• Lipid identity can be deduced from
Chromatograms taken before and after
hydrolysis
39. Mass Spectrometry
• Chromatography fractions or continuous flow can be
monitored by MS
• Accurate masses of intact lipids, specific hydrolysis products,
and internal fragments can be used to deduce structure
40. 10.4 Summary
• Extraction and Chromatography
• Phospholipase hydrolysis
• ID by chromatagraphy, specific hydrolysis
and/or Mass. Spec.
Editor's Notes
FIGURE 10-9 (part 2) Glycerophospholipids. The common glycerophospholipids are diacylglycerols linked to head-group alcohols through a phosphodiester bond. Phosphatidic acid, a phosphomonoester, is the parent compound. Each derivative is named for the head-group alcohol (X), with the prefix "phosphatidyl-." In cardiolipin, two phosphatidic acids share a single glycerol (R 1 and R 2 are fatty acyl groups).
FIGURE 10-21 Vitamin A 1 and its precursor and derivatives. (a) β -Carotene is the precursor of vitamin A 1 . Isoprene structural units are set off by dashed red lines (see p. 359). Cleavage of β -carotene yields two molecules of vitamin A1 (retinol) (b). Oxidation at C-15 converts retinol to the aldehyde, retinal (c), and further oxidation produces retinoic acid (d), a hormone that regulates gene expression. Retinal combines with the protein opsin to form rhodopsin (not shown), a visual pigment widespread in nature. In the dark, retinal of rhodopsin is in the 11- cis form (c). When a rhodopsin molecule is excited by visible light, the 11- cis -retinal undergoes a series of photochemical reactions that convert it to all- trans -retinal (e), forcing a change in the shape of the entire rhodopsin molecule. This transformation in the rod cell of the vertebrate retina sends an electrical signal to the brain that is the basis of visual transduction, a topic we address in more detail in Chapter 12.
FIGURE 10-22 Some other biologically active isoprenoid compounds or derivatives. Units derived from isoprene are set off by dashed red lines. In most mammalian tissues, ubiquinone (also called coenzyme Q) has 10 isoprene units. Dolichols of animals have 17 to 21 isoprene units (85 to 105 carbon atoms), bacterial dolichols have 11, and those of plants and fungi have 14 to 24.
