Transcript Lipids

高等生化學
Advanced Biochemistry
Lipids
陳威戎
Lipids
Lipids
1. Storage Lipids
2. Structural Lipids in Membranes
3. Lipids as Signals, Cofactors, and Pigments
4. Working with Lipids
Storage Lipids
1. Fatty acids are hydrocarbon derivatives.
2. Triacylglycerols are fatty acid esters of glycerol.
3. Triacylglycerols provide stored energy and insulation.
4. Many foods contain triacylglycerols.
5. Waxes serve as energy stores and water repellents.
Fatty acids are hydrocarbon derivatives
Carboxylic acids with hydrocarbon chains ranging from 4 to
36 carbons long (C4 to C36).
Unbranched and fully saturated; one or more double bonds
Nomenclature: chain length; number and position of double
bonds.
The most commonly occurring fatty acids: even numbers of
carbon atoms in an unbranched chain of 12~24 carbons.
The double bonds of polyunsaturated fatty acids are almost
never conjugated, and are in the cis configuration.
The longer to fatty acyl chain and the fewer the double
bonds, the lower is the solubility.
In unsaturated FA, a cis double bond forces a kink in the hydrocarbon
chain. FA with such kinks cannot pack tightly, and their interactions with
each other are weaker, thus having markedly lower melting points.
Polyunsaturated fatty acids (PUFAs)
The packing of fatty acids into stable aggregates
The packing of fatty acids into stable aggregates
Triacylglycerols are fatty acid esters of glycerol
Simple triacylglycerols: same kind of FA in all three positions.
- name after the FA. ex: tristearin, tripalmitin, and triolein.
Mixed triacylglycerols: two or more different FAs
- specify the name and position of each FA
Nonpolar, hydrophobic, essentially insoluble in water.
Lipids have lower specific gravities than water.
Glycerol and triacylglycerol
Triacylglycerol: triglycerides, fats, neutral fats.
Triacylglycerols provide stored energy and insulation
Oily droplets in the aqueous cytosol of most eukaryotic cells
serve as depots of metabolic fuel.
- vertebrates: adipocytes (fat cells)
- plants: germinating seeds
Advantages to using TG as stored fuels:
- carbon atoms are more reduced
- TGs are hydrophobic and unhydrated
In some animals, TGs stored under the skin serve not only as
energy stores but as insulation against low temperature.
Fat stores in cells- guinea pig adipocytes
Fat stores in cellscotyledon cell from seed of Arabidopsis
Many foods contain triacylglycerols
Most natural fats are complex mixtures of simple and mixed
TGs, containing a variety of FAs differing in chain length
and degree of saturation.
- Vegetable oils: unsaturated FAs, liquid at RT
- Catalytic hydrogenation
- Animal fats: saturated FAs, greasy solids at RT
Lipid-rich foods exposed too long to the oxygen in air:
- become spoiled and rancid
- oxidative cleavage of double bonds in FAs
Fatty acid composition of three food fats
Waxes serve as energy stores and water repellents
Biological waxes are esters of long-chain (C14 to C36) FAs with
long-chain (C16 to C30) alcohols.
Melting points (60-100 oC) are generally higher than those of TGs.
Chief storage form of metabolic fuel for some free-floating algae.
Waxes serve a diversity of other functions related to their waterrepellent properties and their firm consistency.
Biological waxes also find a variety of applications in the
pharmaceutical, cosmetic, and other industries. Lanolin,
beeswax, and wax extracted from spermaceti oil are widely
used in the manufacture of lotions, ointments, and polishes.
Biological wax
Lipids
1. Storage Lipids
2. Structural Lipids in Membranes
3. Lipids as Signals, Cofactors, and Pigments
4. Working with Lipids
Structural lipids in membranes
1. Glycerophospholipids are derivatives of phosphatidic acid.
2. Some phospholipids have ether-linked fatty acids.
3. Chloroplasts contain galactolipids and sulfolipids.
4. Archaebacteria contain unique membrane lipids.
5. Sphingolipids are derivatives of sphingosine.
6. Sphingolipids at cell surfaces are sites of biological recognition.
7. Phospholipids and sphingolipids are degraded in lysosomes.
8. Sterols have four fused carbon rings.
Some common types of storage and membrane lipids
Amphipathic; membrane lipid bilayers
Five general types of membrane lipids: glycerophospholipids,
galactolipids and sulfolipids, archaebacterial tetraether lipids,
sphingolipids, and sterols.
L-Glycerol 3-phosphate, the backbone of phospholipids
Glycerophospholipids (Phosphoglycerides)
Glycerophospholipids (Phosphoglycerides)
Ether lipids
About half of the heart phospholipids are plasmalogens.
Ether lipids
A potent molecular signal released from basophils which stimulates
platelet aggregation and the release of serotonin from platelets, also
exerts effects on liver, smooth muscle, heart, uterine, and lung, and
plays an important role in inflammation and the allergic response.
Three glycolipids of chloroplast membranes
Galactolipids are localized in the thylakoid membranes
(inner membranes) of chloroplasts; they make up 70% to
80% of the total membrane lipids of a vascular plant.
Three glycolipids of chloroplast membranes
Phosphate is often the limiting plant nutrient in soil, and
perhaps the evolutionary pressure to conserve phosphate
for more critical roles favored plant that made phosphatefree lipids.
Three glycolipids of chloroplast membranes
Sulfolipids contain a sulfonated glucose residue and
bear a fixed negative charge like that of the phosphate
group in phospholipids.
Archaebacteria contain unique membrane lipids
Long-chain (C32) branched hydrocarbons
Twice the length of phospholipids and sphingolipids
Glycerol dialkyl glycerol tetraethers (GDGTs)
Sphingolipids are derivatives of sphingosine
Sphingosine (4-sphingenine)
Ceramide: structural parent of all sphingolipids
Three subclasses of sphingolipids:
1. Sphingomyelins
2. Glycosphingolipids:
- cerebrosides and globosides (neutral glycolipids)
3. Gangliosides
Sphingolipids
Sphingolipids
Sphingolipids at cell surfaces are sites of biological
recognition
Johann Thudichum discovered sphingolipids a century
ago and named them after the Sphinx.
In human, at least 60 different sphingolipids have been
identified in cellular membranes.
The carbohydrate moieties of certain sphingolipids
define human blood groups.
Gangliosides are concentrated in the outer surface of
cells, where they present points of recognition for
extracellular molecules.
Phosphatidylcholine vs. sphingomyelin
Glycosphingolipids as determinants of blood groups
Phospholipids and Sphingolipids are degraded in
lysosomes
Phospholipase A series
remove one of the two
FAs, producing a
lysophospholipid.
Gangliosides are degraded
by a set of lysosomal
enzymes that catalyze
the stepwise removal of
sugar units, finally
yielding ceramide.
The specificities of phospholipases
Sterols have four fused carbon rings
Steroid nucleus: four fused rings,
three with C6, and one with C5,
which is almost planar and rigid.
Cholesterol is amphipathic.
Similar sterols: stigmasterol in plants
and ergosterol in fungi.
Bacteria cannot synthesize sterols.
All sterols are synthesized from
isoprene subunits.
Steroid hormones
Cholesterol
Bile acids
Inherited human diseases
resulting from abnormal
accumulations of
membrane lipids
Lipids
1. Storage Lipids
2. Structural Lipids in Membranes
3. Lipids as Signals, Cofactors, and Pigments
4. Working with Lipids
Lipids as signals, cofactors, and pigments
1. Phosphatidylinositols and sphingosine derivatives act as
intracellular signals.
2. Eicosanoids carry messages to nearby cells.
3. Steroid hormones carry messages between tissues.
4. Plants use phosphatidylinositols, steroids, and
eicosanoid-like compounds in signaling.
5. Vitamins E and K and the lipid quinones are oxidationreduction cofactors.
6. Dolichols activate sugar precursors for biosynthesis.
Phosphatidylinositols in cellular regulation
Eicosanoids carry messages to nearby cells
Eisosanoids: paracrine hormones
Involved in reproductive function; inflammation, fever, pain, blood
clotting, regulation of blood pressure, gastric acid secretion,
and in a variety of other processes important to human health.
All eicosanoids are derived from arachidonic acid, the 20-C PUFA.
Three classes of eicosanoids:
- Prostaglandins (PG)
- Thromboxanes (Tx)
- Leukotrienes (LT)
Arachidonic acid and some eicosanoid derivatives
In response to hormonal signals, phospholipase A2 cleaves
arachidonic acid (AA) -containing membrane phospholipids to
release AA, the precursor to various eicosanoids.
Arachidonic acid and some eicosanoid derivatives
Nonsteroidal antiinflammatory drugs (NSAIDs): aspirin, ibuprofen, and
meclofenamate - inhibit cyclooxygenase (PGH2 synthase).
Prostaglandins (PG)
Two groups originally defined: PGE (ether-soluble)
PGF (phosphate buffer-soluble)
Affect a wide range of cellular functions by regulating the synthesis
of the intracellular messenger: 3’, 5’-cyclic AMP (cAMP).
Stimulate contraction of the smooth muscle of the uterus.
Affect blood flow to specific organs, the wake-sleep cycle, and the
responsiveness of certain tissues to hormones such as
epinephrine and glucagon.
Elevate body temperature (producing fever), cause inflammation
and pain.
Thromboxanes and Leukotrienes
Thromoboxanes (Tx) - produced by platelets (thrombocytes)
- act in blood clotting and the reduction of blood flow to the site
of a clot.
Leukotrienes (LT) - first found in leukocytes
- three conjugated double bonds
- powerful biological signals
- induces contraction of the muscle lining the respiratory tract
- overproduction causes asthmatic attacks
Steroid hormones carry messages between tissues
Steroids: oxidized derivative of sterols
- more polar than cholesterol
Steroid hormones:
- bind to highly specific receptors
- trigger changes in gene
expression and metabolism
Major groups:
- male and female sex hormones
- produced by the adrenal cortex
- antiinflammatory drugs for
asthma and rheumatoid arthritis
Fat-soluble vitamins
Four vitamin groups: A, D, E, K
All are isoprenoid compounds synthesized by
the condensation of multiple isoprene
units.
Vitamins A (retinol) and D (cholecalciferol) are
hormone precursors.
Vitamins E (tocopherol) and K (phylloquinone
and metaquinone) and the lipid quinones
are oxidation-reduction cofactors.
Vitamin D3 production and metabolism
Regulates calcium uptake in the intestine and calcium levels in
kidney and bone.
Deficiency of Vit. D leads to defective bone formation and rickets.
Vitamin D3 production and metabolism
Vitamin A and its various forms
Function as a hormone and the visual pigment of the vertebrate eye.
Retinoic acid:
- regulates gene expression in the development of epithelial tissue
- active ingredient in the drug tretinoin (Retin-A)
Retinal:
- pigment that initiates the response of rod and cone cells to light
- producing a neuronal signal to the brain
Retinol:
- good dietary sources: fish liver oil, liver, eggs, whole milk, butter
- converted from b-carotene
Deficiency in Vit. A leads to dryness of the skin, eyes, and mucous
membranes; retarded development and growth; night blindness.
Vitamin A1 and its precursor and derivatives
Vitamins E and K and the lipid quinones are
oxidation-reduction cofactors
Vitamin E (tocopherols):
- substituted aromatic ring with a long isoprenoid side chain
- hydrophobic and associates with membrane and lipoproteins
- biological antioxidants (the aromatic ring destroys ROSs)
- eggs, vegetable oils and wheat germ
- laboratory animals fed diets depleted of Vit. E develop scaly
skin, muscular weakness and wasting, and sterility
- Vit. E deficiency in human is very rare
Vitamins E and K and the lipid quinones are
oxidation-reduction cofactors
Vitamin K:
- aromatic ring undergoes a cycle of oxidation and reduction
during the formation of active prothrombin
- prothrombin: protease, convert fibrinogen to fibrin
- deficiency in Vit. K slows blood clotting, rare in human
- Vit. K1 (phylloquinone):
green plant leaves
- Vit. K2 (menaquinone):
bacteria in small intestine
Vitamins E and K and the lipid quinones are
oxidation-reduction cofactors
Warfarin:
- a synthetic compound that inhibits the formation of active
prothrombin
- a potent rodenticide
- also an anticoagulant drug for surgical patients with
coronary thrombosis
Ubiquinone (coenzyme Q) and plastoquinone:
- electron carriers in the oxidation-reduction reactions that
drive ATP synthesis in mitochondria and chloroplast
Dolichols:
- activate sugar precursors for biosynthesis
- anchor sugars to the membrane via hydrophobic interactions
Some other biologically active isoprenoid
compounds or derivatives
Some other biologically active isoprenoid
compounds or derivatives
Lipids
1. Storage Lipids
2. Structural Lipids in Membranes
3. Lipids as Signals, Cofactors, and Pigments
4. Working with Lipids
Working with Lipids
1. Lipid extraction requires organic solvents.
2. Adsorption chromatography separates lipids of
different polarity.
3. Gas-liquid chromatography resolves mixtures of
volatile lipid derivatives.
4. Specific hydrolysis aids in determination of lipid
structure.
5. Mass spectrometry reveals complete lipid structure.
Common procedures in the extraction,
separation, and identification of cellular lipids
Common procedures in the extraction,
separation, and identification of cellular lipids
Common procedures in the extraction,
separation, and identification of cellular lipids
Common procedures in the extraction,
separation, and identification of cellular lipids
Determination of the structure of a fatty acid
by mass spectrometry