From Biolk483

Current revision as of 17:26, 4 November 2009

• The delta of lipid double bond notation stands for double bond, not a certain carbon (Thanks, Neil).

Lipid Diversity

• Why are there so many lipids if one type will suffice to make membranes?
• There are ~1500 different lipids in a single membrane in a single organism.

Phospholipids

• Glycerol + phosphate + 2 fatty acids + one alcohol.
• It generally takes 4 dehydrations to make the phospholipid.
  • These hydrations are reversible.
  • One can use A1 or A2 to get a lisophospholipid: a phospholipid with only one fatty acid
  • Since the lisophospholipid is shaped as a cone (since it only has one fatty acid it is less can-like), several lisophospholipids next to one another start to bend, to cause a dissruption of the normal lamellar phase.
  • Also, the free fatty acid now acts as a soap. These free fatty acids will form a micelle with no water in the center. They can collect small particles in their centers (and hence the washing ability of soap).
    • These micelles will dissolve membrane, so wathc out for lipophospholipids and free fatty acids!
  • Lisophospholipids and free fatty acids clearly aren't very good for you, so it makes sense that they are found in aging and diseased areas (and often as a result of de-isolation --breaking open the compartment in which they were properly housed).

Thylekoid Phospholipids

• We talked about MSDG / DGDG / SDDG earlier
• MGDG forms hexagonal phase, not lamellar phase.

Sphingo Lipids

• These contain sphingosine: a C18 amino alcohol.
  • Sphingosine is highly toxic, so we stick stuff on it to make it safe for the cell (often via esterification).
• We put fatty acids on the sphingolipid via the amine group.
• This addition of a fatty acid gives a compound with two fatty acid chains and a polar head --much like the structural properties of phospholipids.
  • Note, however, that only one of the two hydrophobic chains is variable in a sphingolipid as one is th permanant tail of the sphingosine.
• The most common of the sphingolipids is called sphingomeylin.
  • This lipid is associated with nerves (in fact, most sphingolipids are assocaited with nerves).
• Sphingolipids form the basis of lipid rafts (along with cholesterol)
  • Lipid rafts contain certain proteins that seem to have functions regarding cell signaling.
  • We like the idea of being able to control lipid rafts so we could control cell signaling.

Families of Sphingolipids

1. Ceramide: head group is alcohol of sphingosine
2. Ceribricides: has one sugar (either glucose or galactose, but not both)
3. Gangliocides: have more than one sugar (one of which is always sialic acid which has a negative charge); problems with this sphingolipid often result in lysosome storage diseases

Lipids: Simple Vs. Complex

• We've been talking about complex lipids for a long time now...so we move on to simple lipids now.

Simple Lipids

• Simple lipids often look like polymers of isoprene, but they are not made of isoprene (the stuff in wetsuits)
• Examples: chlorphil, squaline (a precursor to cholesterol), vitamin A, vitamin B, ubiquinone.

Ubiquinone

• AKA: co-enzyme Q, Q10
• This sphingolipid has been shown to be useful against Parkinsons' disease
• The repeating tail of this compound is used as an anchor into the membrane.

Cholesterol

• Cholesterol sits in the membrane and affects the lipids surrounding it.
• Plants and fungi have parallel molecules: stigasterol and ergasterol, repsectively.
  • Note, however, that we do not take up these paralogous sterols so they are not bad for us.
• Cholesterol is a major part of the membrane.
  • It makes up 50-66% of all polar lipids in the plasma membrane.
• We move lots of cholesterol through our body each day: excrete 1100 milligrams, produce 850mg, and consume 250mg.
• The function of cholesterol involves the way it changes the properties of the lipids next to it in the membrane.
  • It acts as a glue that holds the membrane together and makes it less permiable.
• Some kinds of hormones are made from cholesterol, like testosterone and bile salts.

Biological Uses of Lipids

The membrane

• The membrane is a barrier
  • The plasma membrane separates the inside of the cell from the outside of the cell
  • Internal membranes make compartments to keep different reactions in different compartments.
• The membrane is a surface
  • Example: electron transport chain
  • We can make reactions more efficient by putting the correct reagents and enzymes and proteins right next to each other on the lipid surface.
• The membrane identifies the cell
  • The things that stick off the lipid surface give the cell an identity in its environment.

What is holding the bilayer together?

1. Hydrophobic effect

• H2O has to from a surface around the acyl chains if not in bilayer, and it doesn't like this because next to the chain, a water molecule can only make 2 hydrogen bonds but with other water molecules surrounding it, it can make 4 hydrogen bonds. This is surface tension.

2. Entropy at the tails.

• In water, there is no freedom for rotation around all the carbon-carbon bonds in the acyl chains. This is especially important for acy chains with kinks in them (caused by double bonds).

3 & 4. Favoring interactions

• Opposite of hydrophobic effects, this is not about water and acyl chains not liking each other, it is about water liking the polar head and the head groups liking each other.

5. Van der Waals forces

• These are very weak.
• These are interactions between acyl chains.
• A momentary polar distribution of charge in one chain can induce a momentary charge distribution in the chains next to it.

Composition of the Membrane

• The membrane is made up of proteins and lipids and has sugars on the surface (but we'll pretty much ignore the sugars).
• Average by weight: 40% lipid, 60% protein.
  • Where lipids are ~700 AMU and proteins are ~50K AMU.
• Average by number: 50-200 lipids per protein.
  • So we have a very crowded sea of lipid.
• As the number of proteins increases, the biochemical activity increases.
  • Examples: Mitochondrial inner membrane vs myelin sheath
    • Mitochondrial inner membrane has lots of activity, supports the electron transport chain, supports oxidative phosphorylation, supports normal transport, and has 100 different proteins making it 75% protein adn 25% lipid.
    • The myelin sheath supports insulation, has no biochemical activity and had 3 proteins making it 20% protein and 80% lipid.

The Beginnings of Membrane

• 1971: Fluid Mosaic model is presented in a review.
• Nearly all proteins in membranes have a sugar on them
• Many types of membrane-bound proteins (and a lipid):
  • Glycoproteins: a protein with a sugar on it
  • Glycolipid: a lipid with a sugar on it; example: alpha-ganglioside
  • Transmembrane proteins: a protein that crosses the entire membrane, having a presence on the inside of the cell and the outside of the cell.
  • GPI linked proteins: proteins attached to the membrane via Phosphatidyl inositol (a phospholipid).
  • Ectoprotein: a protein that sits slightly embedded on the exterior of the cell membrane.**Endoprotein: a protein that sits slightly embedded on the interior of the cell membrane.
  • Periferal / extrinsic protein: a protein that sits on the exterior surface of the bilipid layer; these wash off very easily with a change of pH or temperature, etc.; example: Cytochrome C
• Endo and ecto proteins may not be a reality --they could just be fragments of transmembrane proteins that we suck at extracting in whole.