Chapter 9 (part 2)

Lipids and Membranes

C 4 C 6 C 8 C 3 C 5 C 7 C 10 C 9 C 12 C 11 C 14 C 13 C 16 C 15 C 18 C 17 H C CH 2

Triacylglycerols (TAG)

O C 2 H 2 C C 1 O

• 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 O C O O C C 2 C 2 C 3 C 3 C 4 C 4 C 5 C 5 C 6 C 6 C C 10 C 9 C C 18 8 12 C 14 C 13 C 16 C 15 C C C 17 7 11 C C 8 C 10 C 12 C 11 14 C 7 C 9 C 13 C 16 C 15 C 18 C 17 O

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

Tail Head

rubber

Poly-isoprene

(Greater than 80 carbons) Rubber (>80,000 Carbons) amorphous Gutta-Percha

The reason rubber is elastic and gutta percha is plastic

Rubber forms an amorphous structure Gutta-percha forms crystalline arrays

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

Membranes

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

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.

After 40 minutes fusion

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

in the bilayer

Proteins

• Integral proteins are strongly imbedded • 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