Lipids and biomembranes

Tomáš Kučeratomas.kucera@lfmotol.cuni.cz

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

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Biological membranesphospholipid bilayer with proteins inserted in it orbound to the surface

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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)

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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