Chapter 12 Lipids and Cell Membranes

The surface of a soap bubble is a bilayer formed by detergent molecules.

The polar heads(red) pack together, leaving the hydrophobic groups(green).

The boundaries of the cells = Biological membranes (the barriers that define the inside and the outside of a cell).

Prevent

molecules leaking out and unwanted molecules from diffusing in.

Allow the cell to take up specific molecules and remove unwanted ones.

Internal membranes : mitochondria, chloroplasts, peroxisomes, lysosomes…

Many common features underlie the diversity of biological membranes 1. Membranes are sheetlike structures , only two molecules thick.(60Å~100Å) 2. Membranes consist of lipids and proteins .

3. Membrane lipids are small molecules that have both hydrophilic and hydrophobic moieties.

4. Specific proteins mediate distinctive functions of membranes (pumps, channels, receptors, energy trasnducers and enzymes).

5. Membranes are noncovalent assemblies .

6. Membranes are asymmetric .

7. Membranes are fluid structures .

8. Most cell membranes are electrically polarized .

12.1 Fatty acids are key constituents of lipids

Fatty acid names are based on their parent hydrocarbons -Fatty acid : long hydrocarbon chains of various lengths and degrees of unsaturation terminated carboxylic acid groups.

-Fatty acid name is derived from the name of its parent hydrocarbon. -Ex> C18 saturated fatty acid = octadecanoic acid (18:0) parent hydrocarbon = octadecane C18 with one double bond = octadecenoic acid(18:1) C18 with two double bond = octadecadienoic acid(18:2) C18 with three double bond = octadecatrienoic acid(18:3) 16:0 18:1

- Fatty acid carbon atoms are numbered starting at the carboxyl terminals.

-Carbon atom 2 = α -Carbon atom 3 = β -Methyl carbon atom at the distal end of the chain = ω -carbon atom -The position of double bond = Δ -Ex> cis-Δ 9 = cis double bond between carbon 9 and 10.

-Double bond counting from the distal end = ω-carbon as number1.

-Ex> ω-3

Fatty acids vary in chain length and degree of unsaturation -16~18 carbon fatty acid are most common.

-The properties of fatty acid and of lipids derived from them are dependent on chain length and degree of saturation .

※ Unsaturated fatty acid = lower melting points saturated fatty acid = higher melting points (same length)

12.2 There are three common types of membrane lipids

※ Three major kinds of membrane lipids 1.Phospholipids

2.Glycolipids

3.Cholesterol

※ Lipids have a variety of biological roles : 1.Fuel molecules.

2.Signal molecules and messengers in signal transduction.

3.Components of membranes.

Phospholipids are the major class of membrane lipids -One or more fatty acids -Platform to which the fatty acids are attached -Phosphate -alcohol -Phospholipids are abundant in all biological membranes.

- Composed with 4 components.

-Platform are built may be glycerol, a three carbon alcohol, or sphingosine.

-Phosphoglyceride : phospholipid derived from glycerol.

-C1 and C2 are esterified to the carboxyl groups of the two fatty acid chains.

-C3 hydroxyl group is esterified to phosphoric acid.

-When no more addition → the simplest fatty acid, phosphatidate

They can be attached to phosphate group as alcohol moieties.

- Sphingomyelin : backbone is sphingsine (amino alcohol that contains a long, unsaturated hydrocarbon chain). -The amino group of the sphingosine bachbone is linked to a fatty acid by amide bond. -The primary hydroxyl group is esterified to phosphorylcholine.

Membrane lipids can include carbohydrate moieties -Glycolipid : sugar containing lipid.

-Derived from sphingosine.

-Amide group is acylated by a fatty acid.

-Primary hydroxyl group is linked to one or more sugars.

-Sugar residues always on the

extracellular side

of the membrane.

Cholesterol is a lipid based on a steroid nucleus -Cholesterol : a lipid with different structure.

steroid, built from four linked hydrocarbon rings.

Hydrocarbon Hydroxyl group -Only found in virtually all animal membranes.

-Almost 25% of the membrane lipids in nerve cell.

-Absent from some intracellular membranes.

Archaeal membranes are built from ether lipids with branched chains - Archaea membranes differ from eukaryotes or bacteria membranes.

1.Nonpolar chains are joined to a glycerol backbone by ether resistant to hydrolysis) than ester linkages.(ether is more 2.Alkyl chains are branched .(branched chain is more resistant to oxidation) 3.Stereochemistry of the central glycerol is inverted .

A membrane lipid is an amphipathic molecule containing a hydrophilic and a hydrophobic moiety -Membrane lipids are amphipathic .

-Contains both a hydrophilic and hydrophobic moiety.

-Overall shape : rectangular.

-Polar head : hydrophilic, red circle.

-Hydrocarbon chain : hydrophobic, straight or wavy lines.

12.3 Phospholipids and glycolipids readily form bimolecular sheets in aqueous media

-Polar head groups favor contact with water, hydrocarbon chains interact with one another. -Micelle : globular structure. -Lipid bilayer : two lipid sheets.

-A micelle is a limited structure (less than 200Å in diameter) -Bimolecular sheet can extend to millimeter or more.

-Lipid bilayers are held together by many noncovalent interactions (hydrophobic), they are cooperative structures .

-Hydrophobic interactions have three significant biological consequences.

1. Extensive 2. Close on themselves (no edges) 3. Self-sealing (no holes) Idealized view Realistic view

Lipid vesicles can be formed from phospholipids -Lipid vesicles , or liposomes are aqueous compartments enclosed by a lipid bilayer. -Can be used to study membrane permeability or to deliver chemicals to cells .

-Liposomes are formed by suspending a suitable lipid, such as phosphatidylcholine, in an aqueous medium. -Sonicating -Vesicles formed.(diameter of about 500Å) -Ions or molecules can be trapped in the vesicles.

-Molecule containing vesicles can be separated by dialysis or gel filtration chromatography .

-A bilayer membrane is formed across a 1-mm hole in a septum that separates two aqueous compartments. -This arrangement permits measurements of the permeability and electrical conductance of lipid bilayers.

Lipid bilayers are highly impermeable to ions and most polar molecules 1/10 9 -Lipid bilayer membranes have a very low permeability for ions and most polar molecules. Why?

-Na+ and K+ traverse the membranes 10 9 times as slowly as does H 2 O.

12.4 Proteins carry out most membrane processes

-Specific proteins mediate membrane functions.

-Membranes differ in their protein contents.

-Ex> Myelin(nerve fiber) = 18% Plasma membrane = chloroplast) = 75% 50% Energy transduction membrane(mitochondria and - Membranes contains many proteins, but has a distinct protein composition .

Proteins associate with the lipid bilayer in a variety of ways - Integral membrane protein : interact with the hydrocarbon chains of membrane lipids(a, b, and c). Can be released by a detergent or an organic solvent.

- Peripheral membrane protein : bound to membranes primarily by electrostatic and hydrogen bond interactions with the head groups of lipid(d and e). Can be released by adding salts or changing the pH.

Proteins can span the membrane with alpha helices -Bacteriorhodopsin : uses light energy to transport protons from inside the cell to outside → proton gradient.

-Almost α helices ; 7 closely packed α helices. -Span its 45Å width.

-Examination of the primary structure of bacteriorhodopsin : most of the amino acid in α helices are

nonpolar(yellow)

and only a very few are

charged(red)

.

-Membrane-spanning α helices are the most common structural motif in membrane proteins.

A channel protein can be formed from beta strands -Porin : built from β strands and contain essentially no α helices. -Each strand is hydrogen bonded to its neighbor in an antiparallel arrangement. -The outside surface of porin is nonpolar.

Interact with the hydrocarbon chains. -The inside of the channel is hydrophilic and is filled with water.

-Alternation of hydrophobic and hydrophilic amino acids along each β strand. Why?

-Hydrophobic – yellow

Embedding part of a protein in a membrane can link the protein to the membrane surface Prostaglandin H 2 synthase-1 : catalyzes the conversion of arachidonic acid into prostaglandin H2 in two steps.

1. Cyclooxygenase reaction 2. Peroxidase reaction - Prostaglandin H 2 promotes inflammation and modulates gastric acid secretion

- Lies along the outer surface of the membrane firmly bound by a set of

α

helices with hydrophobic surfaces that extend from the bottom of the protein into the membrane.

- Partially embedded.

-The location of prostaglandin H 2 synthase-1 in the membrane is crucial to its function.

-The substrate(arachidonic acid) : hydrophobic, generated by the hydrolysis of membrane lipids.

-The substrate reaches the active site through a hydrophobic channel(yellow).

-Drug(aspirin) block the channel.

(transfer acetyl group to Ser530) Membrane proteins: all alpha helix or beta sheet?

Some proteins associate with membranes through covalently attached hydrophobic groups Palmitoyl group attached to a cystein by a thioester bond.

Farnesyl group attached to a cystein at the carboxyl terminus.

mannose GlcNAc By enzymes Glycosylphosphatidylinositol(GPI) anchor attached to the carboxyl terminus.

Transmembrane helices can be accurately predicted from amino acid sequences Phe : hydrophobic amino acid.

unfavorable(+15.5kJ/mol) Arg : positively charged amino acid.

favorable(-51.7kJ/mol)

30Å ≈ 20 residues -Window : the span of 20 residues chosen for this calculation.

-The free energy change for each window is plotted against the first amino acid at the window to create a

hydropathy plot

.

- ≥80kJ/mol in a hydropathy plot : membrane spanning α helix.

- Some membrane proteins contain membrane-spanning features that escape detection by these plot.

12.5 Lipids and many membrane proteins diffuse rapidly in the plane of the membrane

-Lateral diffusion : lipids and many membrane proteins are in lateral motion.

- FRAP(fluorescence recovery after photobleaching) 1. Cell-surface component is labeled with a fluorescent chromophore .

2. A small region is viewed through a fluorescence microscope.

3. Fluorescent molecules in this region are destroyed by laser.

4. This region is monitored.

5. Bleached molecules leave and unbleached molecules enter.

6. Recover the fluorescent intensity in this region.

-The rate of recovery depends on the lateral mobility of the component, which can be expressed in terms of a diffusion coefficient, D .

-The average distance S = (4Dt) 1/2 -Rhodopsin ‘s D = 0.4

μ m 2 /s -Fibronectin’s D = 10 through integrin.) -4 μm 2 /s (because it is anchored to actin filaments on the inside of the plasma membrane

The fluid mosaic model allows lateral movement but not rotation through the membrane -Fluid mosaic model : membranes are two-dimensional solutions of oriented lipids and globular proteins.

- lipid bilayer’s roles : a solvent for integral membrane proteins.

: a permeability barrier .

-The lateral diffusion can be rapid.

-The transition of a molecule from one membrane surface to the other is very slow = transverse diffusion or flip-flop .

Membrane fluidity is controlled by fatty acid composition and cholesterol content -Membrane transport or signal transduction depend to the fluidity of the membrane lipids. - The transition from rigid to the fluid state takes place rather abruptly as the temperature is raised above Tm, the melting temperature.

-Tm depends on the length of the fatty acid chains and on their degree of unsaturation .

-A cis double bond produces a bend in the hydrocarbon chain. This bend interferes with a highly ordered packing of fatty acid chains, and so Tm is lowered.

-Bacteria regulate the fluidity of their membranes by varying the number of double bonds and length of fatty acid chains -In animals, Cholesterol is the key regulator of membrane fluidity, (hydroxyl group : phospholipid head group, hydrocarbon tail : nonpolar core of the bilayer) -Cholesterol disrupts the interactions between fatty acid chain increasing the membrane fluidity. -Cholesterol forms specific complexes with some phospholipids to make lipid rafts

All biological membranes are asymmetric

-Membranes are structurally and functionally asymmetric .

-Different component and enzymatic activity between outer and inner membrane.

※ Na + - K + PUMP -Na + out of the cell.

-K + into the cell.

12.6 Eukaryotic cells contain compartments bounded by internal membranes

Protection -Gram negative bacteria (E.coli) -When staining, pink color -Double membrane -Thin cell wall (peptidoglycan) between them.

-LPS (lipopolysaccharide) -Small molecules permeable due to porin Plasma membrane Permeability barrier -Gram positive bacteria and archaea.

-When staining, violet color -Single membrane surrounded by cell wall (thick peptidoglycan layer)

-Eukaryotic cells are distinguished from prokaryotic cells by the presence of membranes inside the cell that form internal compartments.

(peroxisome, mitochondria, nucleus)

- Membranes must be able to separate or join together so that cells and compartments may take up, transport, and release molecules.

- Breaks off and fuses to form a vesicle .

- The vesicle containing the LDL fuses with a lysosome → degradation.

- Many cells take up molecules through the process of receptor mediated endocytosis proteins .

- Hormones, antibodies, transport ※ LDL receptor : recycled.

※ Cholesterol and amino acid : store or use

Iron is essential but Free iron ions are toxic because of free radical formation. Special transport is necessary

- The reverse process (the fusion of a vesicle to a membrane) is a key step in the release of neurotransmitters from a neuron into the synaptic cleft.