Chapter 9 (part 2)

Lipids and Membranes

Triacylglycerols (TAG)

• Fats and oils• Impt source of metabolic fuels• Because more reduced than

carbos, oxidation of TAG yields more energy (16 kJ/g carbo vs. 37 kJ/g TAG)

• Americans obtain between 20 and 30% of their calories from fats and oils. 70% of these calories come from vegetable oils

• Insulation – subcutaneous fat is an important thermo insulator for marine mammals

C9

CH2HCH2C

C16

O O

C OC1

O

C2

C3

C4

C5

C6

C7

C8

C10

C11

C12

C13

C14

C15

C17

C18

C9

C16

C2

C3

C4

C5

C6

C7

C8

C10

C11

C12

C13

C14

C15

C17

C18

O

C O

C9

C16

C2

C3

C4

C5

C6

C7

C8

C10

C11

C12

C13

C14

C15

C17

C18

Olestra

•Olestra is sucrose with fatty acids esterified to –OH groups

•digestive enzymes cannot cleave fatty acid groups from sucrose backbone

•Problem with Olestra is that it leaches fat soluble vitamins from the body

Head

Tail

rubber

amorphous

Poly-isoprene Poly-isoprene (Greater than 80 carbons)(Greater than 80 carbons)

Rubber (>80,000 Carbons)

Gutta-Percha

The reason rubber is elastic and gutta percha is plastic

Gutta-percha forms crystalline arrays

Rubber forms an amorphous structure

Steroids

• Based on a core structure consisting of three 6-membered rings and one 5-membered ring, all fused together

• Triterpenes – 30 carbons• Cholesterol is the most common steroid

in animals and precursor for all other steroids in animals

• Steroid hormones serve many functions in animals - including salt balance, metabolic function and sexual function

cholesterol

• Cholesterol impt membrane component

• Only synthesized by animals

• Accumulates in lipid deposits on walls of blood vessels – plaques

• Plaque formation linked to cardiovascular disease

Steroids

Many steroids are derived from cholesterol

• Barrier to toxic molecules • Help accumulate nutrients • Carry out energy transduction • Facilitate cell motion • Modulate signal transduction • Mediate cell-cell interactions

Membranes

The Fluid Mosaic Model

• The phospholipid bilayer is a fluid matrix

• The bilayer is a two-dimensional solvent

• Lipids and proteins can undergo rotational and lateral movement

• Two classes of proteins: – peripheral proteins (extrinsic proteins) – integral proteins (intrinsic proteins)

The Fluid Mosaic Model

Motion in the bilayer• Lipid chains can bend, tilt and rotate • Lipids and proteins can migrate

("diffuse") in the bilayer • Frye and Edidin proved this (for

proteins), using fluorescent-labelled antibodies

• Lipid diffusion has been demonstrated by NMR and EPR (electron paramagnetic resonance) and also by fluorescence measurements

• Diffusion of lipids between lipid monolayers is difficult.

fusion

After 40 minutes

Flippases• Lipids can be moved from one

monolayer to the other by flippase proteins

• Some flippases operate passively and do not require an energy source

• Other flippases appear to operate actively and require the energy of hydrolysis of ATP

• Active flippases can generate membrane asymmetries

Membranes are Asymmetric

In most cell membranes, the composition of the outer monolayer is quite different from that of the inner monolayer

Membrane Phase Transitions

• Below a certain transition temperature, membrane lipids are rigid and tightly packed

• Above the transition temperature, lipids are more flexible and mobile

• The transition temperature is characteristic of the lipids in the membrane

Phase Transitions

• Only pure lipid systems give sharp, well-defined transition temperatures

• Red = pure phospholipid

• Blue = phopholipid + cholesterol

Structure of Membrane Proteins

• Integral (intrinsic) proteins • Peripheral (extrinsic) proteins • Lipid-anchored proteins

Peripheral Proteins

• Peripheral proteins are not strongly bound to the membrane

• They can be dissociated with mild detergent treatment or with high salt concentrations

Integral Membrane Proteins

• Integral proteins are strongly imbedded in the bilayer

• They can only be removed from the membrane by denaturing the membrane (organic solvents, or strong detergents)

• Often transmembrane but not necessarily

• Glycophorin, bacteriorhodopsin are examples

Seven membrane-spanning alpha helices, connected by loops, form a bundle that spans the bilayer in bacteriorhodopsin.

The light harvesting prosthetic group is shown in yellow.

Bacteriorhodopsin has loops at both the inner and outer surface of the membrane.

It displays a common membrane-protein motif in that it uses alpha helices to span the membrane.

Lipid-Anchored Proteins

• Four types have been found: – Amide-linked myristoyl

anchors – Thioester-linked fatty acyl

anchors – Thioether-linked prenyl

anchors – Glycosyl phosphatidylinositol

anchors

Amide-Linked Myristoyl Anchors

• Always myristic acid • Always N-terminal • Always a Gly residue that links

Thioester/ester-linked Acyl Anchors

• Broader specificity for lipids - myristate, palmitate, stearate, oleate all found

• Broader specificity for amino acid links - Cys, Ser, Thr all found

Thioether-linked Prenyl Anchors

• Prenylation refers to linking of "isoprene"-based groups

• Always Cys of CAAX (C=Cys, A=Aliphatic, X=any residue)

• Isoprene groups include farnesyl (15-carbon, three double bond) and geranylgeranyl (20-carbon, four double bond) groups