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Lipids and biomembranes
Tomáš Kuč[email protected]
Department of Medical Chemistry and Clinical Biochemistry2nd Faculty of Medicine, Charles University in Prague and Motol University
Hospital
2017
Lipids
Definitionnon-polar (hydrophobic) compounds of biologicalorigin, soluble in organic solvents (in water limitedly ornot at all)
Major rolesstructural components of biological membranesenergy storage (triacylglycerols)thermal (and electric) insulatorsprotective layers against infection, clashes anddessicationvitamins and hormones and their precursorsbile acids – lipid solubilization
Fatty acids
FAimportant components of most other lipidsa hydrocarbon chain (4–36 C) with a carboxyl at oneendamphipathic
non-polar endpolar enda 16-C fa�y acid: CH3 (CH2)14 COO−
saturated or unsaturatedfree rotation around C–C bondsno rotation around C=C bonds
esterified or “free”salts with alkali metals – soaps
Fatty acids
of various length
SCFA (< 6 C)MCFA (6–12 C)LCFA (12–22 C) (14–20)VLCFA (> 22 C)
lower (< 10 C)higher (> 12 C)
Fatty acids
Example: octadeca-9,12-dienoic acid
OH
O
1α
2
β
3γ
4
nω
18-C FA with two cis double bonds in positions 9 and 12
linoleic acid (9,12-octadecadienoic)
cis,cis-C18:2 ∆9,12 or C18:2 cis,cis-ω6or cis,cis-C18:2 n−6 or all cis-C18:2 ∆9,12 or C18:2-ω6or all cis-C18:2(9,12)or C18:2(9c,12c)
Fatty acids
usuallylinear hydrocarbon chainan even number of carbon atomsdouble bonds in cis configuration
a rigid kink at each C C bond
OH
O
stearic acid
acid C18:1(11c)
oleic acid
linoleic acid
FA melting points decrease withshorter chainsunsaturationvicinity of the first C=C to the carboxyl
Some common fatty acids
Triviální název Zkratka Systematický název m.p. (◦C) Vzorec
Saturatedlauric C12:0 dodecanoic 44.2
COOH
myristic C14:0 tetradecanoic 52.0COOH
palmitic C16:0 hexadecanoic 63.1COOH
stearic C18:0 octadecanoic 69.6COOH
arach(id)ic C20:0 eicosanoic 75.4COOH
behenic C22:0 docosanoic 81.0COOH
lignoceric C24:0 tetracosanoic 84.2COOH
With one double bond (MUFA)palmitoleic C16:1ω7 hexadec-9-enoic −0.5 COOH
oleic C18:1ω9 oktadec-9-enoic 13.4 COOH
erucic C22:1ω9 docosa-13-enoic COOH
nervonic C24:1ω9 tetracosa-15-enoic 39.0 COOH
With two double bondslinoleic C18:2ω6 octadeca-9,12-dienoic −9.0
COOH
With three double bonds (↓PUFA↓)α-linolenic C18:3ω3 octadeca-9,12,15-trienoic −17.0 COOH
γ-linolenic C18:3ω6 octadeca-6,9,12-trienoic COOH
With four double bondsarachidonic C20:4ω6 eicosa-5,8,11,14-tetraenoic −49.5
COOH
With five double bondstimnodonic (EPA) C20:5ω3 eicosa-5,8,11,14,17-pentaenoic −54.0 COOH
clupanodonic (DPA) C22:5ω3 docosa-7,10,13,16,19-pentaenoic COOH
With six double bondscervonic (DHA) C22:6ω3 docosa-4,7,10,13,16,19-hexaenoic
COOH
essential: linoleic and α-linolenic
Some less common fatty acids
Triviální název Zkratka Systematický název ω Vzorec
With odd-numbered chainC13:0 tridecanoic COOH
C15:0 pentadecanoic COOH
C17:0 heptadecanoic COOH
C17:1(9c) cis-heptadec-9-enoic 8COOH
Branched (MUFA)iso-tridecanoic isoC13:0 11-methyldodecanoic 7
COOH
iso-tetradecanoic isoC14:0 12-methyltridecanoic COOH
iso-pentadecanoic isoC15:0 13-methyltetradecanoicCOOH
iso-hexadecanoic isoC16:0 14-methylpentadecanoic COOH
iso-heptadecanoic isoC17:0 15-methylhexadecanoicCOOH
anteiso-tridecanoic anteisoC13:0 10-methyldodecanoicCOOH
anteiso-pentadecanoic anteisoC15:0 12-methyltetradecanoicCOOH
anteiso-heptadecanoic anteisoC17:0 14-methylhexadecanoicCOOH
phytanic 3,7,11,15-tetramethylhexadecanoic COOH
pristanic 2,6,10,14-tetramethylpentadecanoic COOH
Conjugated linoleic acid (CLA)C18:2(9c,11t) 9-cis,11-trans-octadeca-9,11-dienoic 8 COOH
C18:2(10t,12c) 10-trans,12-cis-octadeca-10,12-dienoic 7 COOH
With a triple bondtariric C18:1(6a) octadec-6-ynoic
COOH
Some really exotic fatty acids
e.g. haliclonyne (47C FA): 14-oxo-4,5,6,28,33,37,42,45-octahydroxy-trans-26,trans-43-dien-2,31,34,46-tetrayn-heptatetracontanoicacid
HOOC
OH
OH
OH
(CH2)7
O
(CH2)10
OH
OH
OH
(CH2)4
OH
OH
cyclopropane tocyclohexane ringepoxy-, cyclic peroxides,–SH, disulfides. . .fa�y alcohols – similardiversity
HOOC
HOOC
HOOC
Overview of lipids
Simple lipids – esters of FA with alcoholsfats & oils (acylglycerols, glycerides): alcohol = glycerolwaxes: alcohol = long-chain (mono)alcohol
Complex lipids – esters FA+alcohols + other itemsphospholipids – FA + glycerol + phosphate + somethingglycolipids – contain sugars
glycoacylglycerols – FA + glycerol + sugarglycosphingolipids – FA + sphingosine + sugar (+ sialic acid)
sphingolipids – contain ceramide (amide FA+sphingosine)sphingomyelins – ceramide + phosphocholineglycosphingolipids – see above
Derived lipidsother biological hydrophobic substances, e.g. steroids,eicosanoids, docosanoids, carotenoids and otherterpenoids, lipophilic vitamins
Simple lipids
Esters of fa�y acids with alcohols
Waxes (cerides)the alcohol is long, monovalent – “fa�y”the “most fa�y” of the lipidsin animals final metabolitesusually a protective function
plant cuticulelanolinbeeswax
beeswax – main component C15H31COOC30H61
myricyl palmitate – triacontyl hexadecanoatecarnauba wax – main component C25H51COOC30H61
myricyl cerotate – triacontyl hexacosanoate
Simple lipidsOHCH2
CH OH
CH2 OH
glycerol
HO CO R
FA
O CO R1CH2
CH O CO R2
CH2 O CO R3
triacylglycerol
Triacylglycerols(triglycerides, neutral fats and oils)the most abundant dietary lipidsenergy storage
reduced“compact” (dehydrated)
protective layersglycerol “backbone” + 3 esterified FAmost are “mixed ”
Complex lipids
sphingolipids, glycerolipidsphospholipids
glycerophospholipids (PE, PS, PC, PG, DPG, PI;plasmalogens)sphingomyelins
glycolipidsglycoacylglycerolsglycosphingolipids
cerebrosidesgangliosides
all complex lipidsinclude non-polar FA chains (“tails”)include polar region (glycerol, FA carbonyls, usually Pi,the “polar head” group⇒ they are amphipathic
Glycerophospholipids(phosphoglycerides)
common constituents of biological membranesglycerol “backbone”hydroxyls at C1 & C2 esterified with fa�y acidsC3 esterified with Pi
Phosphatidic acids
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O–
the simplest phospholipidsonly small amounts in themembranesonly intermediates in thesynthesis of triacylglycerolsand glycerophospholipids
Glycerophospholipids
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O X
polar head – usually, Pi is further esterified to OH of apolar head group (signed X in the figure) – e.g. serine,choline, ethanolamine, glycerol, or inositolThe 2 fa�y acids tend to be non-identical.amphipathic (complex polar region)
Glycerophospholipids
Phosphatidylinositols (PI)
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O
OHOH
OH
OHOH
membrane lipidscellular signaling molecules
Phosphatidylcholines (lecithins, PC)
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O CH2 CH2 N+
CH3
CH3
CH3
common membranelipids
Glycerophospholipids
Plasmalogens
R2 C
O
O CH
CH2 O CH R1
CH2 O P
O
O–
O X
glycerol enol-ether phospholipidsin mammals
R1 (the fa�y alcohol) usually C16:0, C18:0, or C18:1R2 usually PUFAX=usually ethanolamine or choline (or serine)
brain and musclesPAF (platelet activating factor) – platelet aggregation
R1 = C16:0, R2 = acetyl, X= cholinR2 acetyl⇒ higher solubility
Sphingolipidsderivatives of the amino alcohol sphingosine
H2C
OHHC
NH2
CH
OH
CH
CH
CH2)12 (10−14)(
CH3sphingosine
H2C
OHHC
NH
CO
R
CH
OH
CH
CH
CH2)12(
CH3ceramide
amides of sphingosine with FA = ceramidesother sphingolipids include a polar head group,esterified to the terminal OH of the sphingosine.
Sphingolipids
Sphingomyelins (phosphosphingolipids)
H2C
O
P O–
O
OH2CH2C+N
CH3
CH3
CH3
HC
NH
CO
R
CH
OH
CH
CH
CH2)12(
CH3
ceramides with the phosphocholine orphosphoethanolamine “head” groupcommon constituent of plasma membranesin brain and nerve tissue
Glycosphingolipids
Cerebrosides
H2C
O
Glc (or β,D-Gal)β,D-
HC
NH
CO
R
CH
OH
CH
CH
CH2)12(
CH3
ceramides with a monosaccharidesuch as glucose or galactose aspolar head group
GangliosidesNHC
O
CH3
OHOH
COOHO
OHOH
CH2 OH
N-acetylneuraminic acid
ceramides with a polar headgroup that is a complexoligosaccharide, containinga sialic acid
common in the outer layer of the plasma membranesugar chains extend outwards
Glycolipids
glycoacylglycerols
R2 C
O
O CH
CH2 O C
O
R1
CH2 O
β-D-Gal 1,6-α-D-Gal
mono- and digalactosyl diacylglycerols
R2 C
O
O CH
CH2 O C
O
R1
CH2 O
OH
OH
OH
CH2SO3–
O
sulfoquinovosyl diacyl glycerols
important constituents of plant membranesthylakoid membrane
Derived lipids
Isoprenoids
isoprene
geranene
farnesene
geranylgeranene
phytene
squalene
phytoene
monoterpenes (menthol, limonene, camphor, pinene,geraniol)sesquiterpenes (humulene, zingiberene)diterpenes (geranylgeraniol, taxadiene, kahweol,cafestol, phytol (chains of chlorophyll, vitamins E and K)triterpenes (steroids)tetraterpenes (carotenoids⇒ vitamin A)
Steroids – cholesterol
HO3 4 5 6 7
814 15
1617
H321C
2022
23 2425
H327C
26CH3
13
18CH3
1211
910
19CH3
12
important constituent of cell membranesa rigid ring system and a short branched hydrocarbon“tail”hydrophobicamphipathy (weak) conferred by the –OHprecursor of
D vitaminbile acidssex hormonesadrenocortical hormones
Biological membranes
lipids in polar environments – aggregation tocomplexes in which polar regions are in contact withwater and hydrophobic regions away from water.possible molecular arrangements:
various micelle structuresspherical micelles – stable form of FAa bilayer – stable form for amphipathic lipids such asphospholipids
zdro
j
Biological membranesphospholipid bilayer with proteins inserted in it orbound to the surface
zdro
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integral proteins – embedded in the bilayertrans-membrane
peripheral proteins – bound to the surface of themembranemany of the proteins and lipids carry oligosaccharidechains
Biological membrane fluidity
the interior of a lipid bilayer is normally highly fluid.liquid (fluid) state – hydrocarbon chains disorderedand in constant motion (higher temperatures)crystalline state – fa�y acid tails are fully extended,packing is highly ordered (lower temperatures)
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Biological membrane fluidityFA types – see aboveCholesterol inserts into bilayer membranes
hydroxyl group oriented outpolar environmenthydrogen bonds with polar heads of membrane lipids
hydrophobic ring system adjacent to FA chains ofmembrane lipids
hydrophobic interactionsrather rigid molecule – interactions with membrane lipidhydrocarbon chains decreases the membrane fluidity
HO
CH3
H3C
CH3
CH3
CH3
zdro
j
Biological membrane assymmetry
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lateral mobility of a lipid is hightransversal mobility (flip-flop)
of lipids is very lowof proteins has never been observed
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Biological membrane assymmetry
the two leaflets are di�erent⇒ assymmetry inlipid compositionprotein composition and orientationsaccharides of glycoproteins and glycolipidesfunction
Membrane microdomainslipid ra�s
moresphingolipids (by 50 %)cholesterol (3–5×)saturated FA
lessphosphatidylcholine (⇒∼ equal choline)
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Glycerophospholipids(phosphoglycerides)
common constituents of biological membranesglycerol “backbone”hydroxyls at C1 & C2 esterified with fa�y acidsC3 esterified with Pi
Phosphatidic acids
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O–
the simplest phospholipidsonly small amounts in themembranesonly intermediates in thesynthesis of triacylglycerolsand glycerophospholipids
Glycerophospholipids
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O X
polar head – usually, Pi is further esterified to OH of apolar head group (signed X in the figure) – e.g. serine,choline, ethanolamine, glycerol, or inositolThe 2 fa�y acids tend to be non-identical.amphipathic (complex polar region)
GlycerophospholipidsPhosphatidylinositols (PI)
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O
OHOH
OH
OHOH
membrane lipidscellular signaling molecules
Phosphatidylcholines (lecithins, PC)
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O CH2 CH2 N+
CH3
CH3
CH3
common membranelipids
Glycerophospholipids
Phosphatidylinositols (PI)
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O
OHOH
OH
OHOH
membrane lipidscellular signaling molecules
Phosphatidylcholines (lecithins, PC)
R2 C
O
O CH
CH2 O C
O
R1
CH2 O P
O
O–
O CH2 CH2 N+
CH3
CH3
CH3
common membranelipids
GlycerophospholipidsPlasmalogens
R2 C
O
O CH
CH2 O CH R1
CH2 O P
O
O–
O X
glycerol enol-ether phospholipidsin mammals
R1 (the fa�y alcohol) usually C16:0, C18:0, or C18:1R2 usually PUFAX=usually ethanolamine or choline (or serine)
brain and musclesPAF (platelet activating factor) – platelet aggregation
R1 = C16:0, R2 = acetyl, X= cholinR2 acetyl⇒ higher solubility
Sphingolipids
derivatives of the amino alcohol sphingosine
H2C
OHHC
NH2
CH
OH
CH
CH
CH2)12 (10−14)(
CH3sphingosine
H2C
OHHC
NH
CO
R
CH
OH
CH
CH
CH2)12(
CH3ceramide
amides of sphingosine with FA = ceramidesother sphingolipids include a polar head group,esterified to the terminal OH of the sphingosine.
Sphingolipids
derivatives of the amino alcohol sphingosine
H2C
OHHC
NH2
CH
OH
CH
CH
CH2)12 (10−14)(
CH3sphingosine
H2C
OHHC
NH
CO
R
CH
OH
CH
CH
CH2)12(
CH3ceramide
amides of sphingosine with FA = ceramidesother sphingolipids include a polar head group,esterified to the terminal OH of the sphingosine.
SphingolipidsSphingomyelins (phosphosphingolipids)
H2C
O
P O–
O
OH2CH2C+N
CH3
CH3
CH3
HC
NH
CO
R
CH
OH
CH
CH
CH2)12(
CH3
ceramides with the phosphocholine orphosphoethanolamine “head” groupcommon constituent of plasma membranesin brain and nerve tissue
GlycosphingolipidsCerebrosides
H2C
O
Glc (or β,D-Gal)β,D-
HC
NH
CO
R
CH
OH
CH
CH
CH2)12(
CH3
ceramides with a monosaccharidesuch as glucose or galactose aspolar head group
GangliosidesNHC
O
CH3
OHOH
COOHO
OHOH
CH2 OH
N-acetylneuraminic acid
ceramides with a polar headgroup that is a complexoligosaccharide, containinga sialic acid
common in the outer layer of the plasma membranesugar chains extend outwards
Glycosphingolipids
Cerebrosides
H2C
O
Glc (or β,D-Gal)β,D-
HC
NH
CO
R
CH
OH
CH
CH
CH2)12(
CH3
ceramides with a monosaccharidesuch as glucose or galactose aspolar head group
GangliosidesNHC
O
CH3
OHOH
COOHO
OHOH
CH2 OH
N-acetylneuraminic acid
ceramides with a polar headgroup that is a complexoligosaccharide, containinga sialic acid
common in the outer layer of the plasma membranesugar chains extend outwards
Glycolipidsglycoacylglycerols
R2 C
O
O CH
CH2 O C
O
R1
CH2 O
β-D-Gal 1,6-α-D-Gal
mono- and digalactosyl diacylglycerols
R2 C
O
O CH
CH2 O C
O
R1
CH2 O
OH
OH
OH
CH2SO3–
O
sulfoquinovosyl diacyl glycerols
important constituents of plant membranesthylakoid membrane
Glycolipids
glycoacylglycerols
R2 C
O
O CH
CH2 O C
O
R1
CH2 O
β-D-Gal 1,6-α-D-Gal
mono- and digalactosyl diacylglycerols
R2 C
O
O CH
CH2 O C
O
R1
CH2 O
OH
OH
OH
CH2SO3–
O
sulfoquinovosyl diacyl glycerols
important constituents of plant membranesthylakoid membrane
Derived lipidsIsoprenoids
isoprene
geranene
farnesene
geranylgeranene
phytene
squalene
phytoene
monoterpenes (menthol, limonene, camphor, pinene,geraniol)sesquiterpenes (humulene, zingiberene)diterpenes (geranylgeraniol, taxadiene, kahweol,cafestol, phytol (chains of chlorophyll, vitamins E and K)triterpenes (steroids)tetraterpenes (carotenoids⇒ vitamin A)
Steroids – cholesterol
HO3 4 5 6 7
814 15
1617
H321C
2022
23 2425
H327C
26CH3
13
18CH3
1211
910
19CH3
12
important constituent of cell membranesa rigid ring system and a short branched hydrocarbon“tail”hydrophobicamphipathy (weak) conferred by the –OHprecursor of
D vitaminbile acidssex hormonesadrenocortical hormones