Lipids: Chapter 10

• Major characteristic: hydrophobicity (water insolubility)– But typically amphipathic

• Lipophilic (hydrophobic) chain• Polar/charged (hydrophilic) headgroup

“Fatty acids”

• “Fatty” = lipid component: chain of hydrocarbons, “acid” = carboxylic acid (hydrophilic headgroup)

• Lipids components interact via hydrophobic and van der Waals forces– Stronger forces = higher melting points, less fluidity

• Variation in chains: determines physical properties of the lipid portion (mp, fluidity, water solubility)– Length: ~4-40 carbons in the backbone

• Longer chains = stronger forces

– “Saturation”: refers to # double bonds (fully saturated means saturated with hydrogens, no double bonds)

• Unsaturation: lack of free rotation around double bond– Typically in ‘cis’ conformation: introduces a kink in the chain– Reduces intermolecular interactions

Saturation

Derivation of the carboxylic acid

• Commonly ester linkage to glycerol– Three positions for acylation

Storage lipids

• Energy storage: triacylglycerol– Three fatty acid groups linked to glycerol– Efficient relative to sugar

• Energy in C-C bonds is higher• Water insolubility aids storage• But sugars are better as ‘quick’ sources of energy

• Waxes– Typically solid (vs. oils)

• What types of lipids will form waxes?– Length? Saturation?

Membrane Lipids

• Lipid bilayer: lipid component cluster together, polar headgroup exposed to aqueous environments– Again, these lipids are amphipathic

• Types of membrane lipids:– Glycerophosphates– Galactolipids/sulfolipids– Tetraether lipids– Sphingolipids– Sterols

Glycerophospholipids

• Glycerol: three –OH groups

• Glycerophospholipids:1. Phosphate plus polar/charged group

2. Fatty acid ester

3. Fatty acid ester

Polar headgroup constituents of GPLs

-3?

Phosphatidylinositol can be phosphorylated enzymatically on multiple –OH groups

“Combinatorial complexity”

PI (net -1)

PI 4-kinase

PI (4) P

PI(4)P 5-kinase

adds phosphateto 4 position

adds phosphateto 5 position

PI (4,5) P2

PI(4,5)P2 3-kinase

PI(3,4,5)P3

(-2) (-3)

(-4)

Galactolipids

• Plant-specific

• Similar to glycerophospholipids– Glycerol “backbone” with two fatty acid esters– Polar headgroup: no phosphate linkage,

typically galactose (polar) or sulfonated galactose (charged)

Sphingolipids

• Common part of mammalian membranes• Sphingosine backbone

– Similar idea as glycerol– Intrinsic long chain– Fatty acid attached in amide linkage– Polar headgroup

Mammalian cell membrane

Liver cell plasma membrane: Percent of total lipid by mass

• Phosphatidylcholine: 24• Sphingomyelin: 19• Cholesterol: 17• Phosphatidylethanolamine: 7• Glycolipids: 7• Phosphatidylserine: 4• Others: 22

Alberts: The Molecular Biology of the Cell

But, lipid composition is dynamic

eg. phosphorylation of phosphatidylinositoleg. enzymatic addition/removal of lipid headgroupseg. removal/addition (typically through vesicles) of

lipids: changing fatty acid composition

Why multiple compositions?

ie. what effect do lipids have on cell function?

Effects of lipid composition of cell physiology

1. Membrane fluidity• Length/saturation of the fatty acid chain• Attraction/repulsion among headgroups

2. Activity of integral membrane proteins

•Lipids act as the solvent•Composition of the membrane can have drastic effects on the proteins’ activities

3. Binding sites for peripheral membrane proteins

Effects of lipid composition of cell physiology

PH domain from DAPP1 bindingto PI (3,4,5)P3

Effects of lipid composition of cell physiology

4. Precursors to other molecules:• Membrane acts as a store of other important compounds:

typically released enzymatically

Hydrolysis by phospholipase enzymesPhospholipase A1/2: yield glycerophospholipid plus fatty acid

Phospholipase C: yields diacylglycerol plus free phosphorylated headgroup

Phospholipase D: yields phosphatidic acid (ie. phosphorylated DAG) plus free headgroup

Role of cholesterol

• Amphipathic compound: incorporates into lipid bilayer• Disrupts close packing of lipid chains: increases

membrane fluidity• Precursor to steroid hormones (eg. estrogen,

testosterone)• Excess (water-insoluble) cholesterol

can clog the arteries during

transport