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Chapter 5

Make up of Plasma Membrane

• Made up of lipid and protein molecules

• Lipids are the main component in the membrane, especially phospholipids

Phospholipids and Glycerophospholipids

• Phospholipid: Contains a phosphate group.

• Glycerophospholipid: Contains glycerol and phosphate groups.

  • What is glycerol? A poly-alcohol with 3 carbons (propane-1,2,3-triol).

  • What is an Acyl group? A bunch of carbons and hydrogens (long chain fatty acids, 8-24 carbons).

How are Glycerophospholipids Made?

• Two acyl chains (long-chain fatty acids) attach to a glycerol backbone.

• The glycerol backbone also has a phosphate group attached.

• Two fatty acids are esterified to the sn-1 and sn-2 positions of glycerol.

• A phosphate group ($PO_4^{3-}$) is attached to the sn-3 position of glycerol via a phosphodiester bond.

Bonds in Glycerophospholipid Formation

• Reaction of carboxylic acid + alcohol: Produces an ester bond.

• Reaction of an acid (e.g., $H<em>3PO</em>4$ - phosphate) + alcohol: Produces a phosphoester bond.

• Phosphodiester bond: An ester bond on each side of the phosphate group in glycerophospholipids.

Polar and Nonpolar Characteristics of Glycerophospholipids

• Amphipathic: A molecule with both polar (hydrophilic - water-loving) and nonpolar (hydrophobic - water-fearing) components.

• Glycerophospholipid is an amphipathic molecule.

• The phosphate and attached head group form the polar 'head' (negatively charged at physiological pH).

• The two fatty acid chains form the nonpolar 'tails'.

• Choline: Ethanol with an $(+N-CH_3)$ bond, often a head group.

Behavior of Phospholipids in Water

• When phospholipids are introduced to an aqueous environment, they spontaneously arrange.

• Clathrate: A cage-like structure formed by water molecules around the non-polar components of a phospholipid molecule.

• Glycerol molecules shed these organized water molecules when they aggregate.

• Thermodynamic property increased: The entropy of water dramatically increases when it goes from an organized clathrate to bulk solvent.

• Main driving force: The dramatic increase in entropy of the water system.

Formation of the Lipid Bilayer

• The phospholipid bilayer is the fundamental structure of biological membranes.

• It forms spontaneously in aqueous environments.

• Bilayer Composition: Composed of two leaflets.

  • One leaflet faces the exterior.

  • The other leaflet faces the interior.

Other Lipids Present

• Cholesterol: Also considered amphipathic.

  • Most of the molecule is hydrophobic (all C-H bonds).

  • One end is hydrophilic due to a hydroxyl (OH) group.

Molecular Motions in Phospholipid Bilayers

• The membrane is not stationary; there is always motion.

• Small Non-Polar molecules: CAN diffuse past the membrane.

• Types of motion:

  • Rotational Motion: Lipids rapidly rotate around their long axis.

  • Lateral Diffusion (Transverse Motion): Lipids diffuse rapidly within the same leaflet.

  • Transverse Diffusion (Flipping Between Leaflets): Movement of a lipid from one leaflet to the other.

    • This is a much slower process, energetically unfavorable.

    • Often catalyzed by enzymes like Flippases, Floppases, or Scramblases (which rearrange the membrane by flipping lipids).

• Condition for motion to stop: Absolute zero (0 Kelvin or $-273.15$ degrees Celsius).

Nature of Proteins in a Membrane

• Peripheral membrane proteins: Associated with the surface of the membrane.

• Integral membrane proteins: Associated and embedded within the membrane.

  • Ditopic Integral membrane proteins: Span the membrane completely (cross both leaflets).

    • R groups inside membrane: Nonpolar R groups.

    • Groups on opposite ends (outside): Polar groups (N and C terminus).

  • Monotopic Integral membrane proteins: Ends of the protein only cross or associate with one side, not both.

• Lipid-Anchored Proteins: Covalently attached to a lipid in the membrane, but the protein itself doesn't directly enter the bilayer.

Jobs Proteins can have (e.g., Channel Proteins)

• Channel Proteins: Facilitate transport across the membrane.

  • Uniporter: Passage goes in one direction, for one type of molecule.

  • Symporter: Passage goes in two directions (two molecules) across the membrane, in the same direction.

  • Antiporter: Passage goes in two directions (two molecules) across the membrane, in opposite directions.

Membrane Heterogeneity (Figure 5.6)

• The makeup (lipid and protein) is not homogenous from one membrane to another.

• Examples: Plasma membrane vs. Mitochondria vs. ER membranes.

• Why different?: Each membrane has a different function, needing a different structure.

Membrane Dynamics

• Possible to fuse a membrane with another membrane, or split (e.g., during processes like Mitosis).

Signal Transduction (Figure 5.8)

• Definition: The process by which a chemical signal on one side of a membrane gets transmitted to the other side.

• A cell producing a signal molecule.

• The signal molecule (ligand) binds to a receptor protein on the surface of another cell.

• Binding causes a change in protein conformation.

• This change can activate or inactivate another protein.

• Kinase: An enzyme that catalyzes the ATP-dependent phosphorylation of a substrate.

• Cascade: One event triggering another in a sequence.

Signal Transduction Pathway Example (Figure 5.9 - AKA Pathway)

1. A ligand (e.g., epinephrine) binds to a cell surface receptor (e.g., $B$-adrenergic receptor).

2. The hormone-receptor complex causes the alpha subunit of a G protein to exchange bound GDP for GTP ($D \rightarrow T$).

3. The activated alpha subunit dissociates and activates adenylate cyclase.

4. Adenylate Cyclase produces cAMP from ATP (catalyzes conversion of ATP to 5'3 prime cAMP).

5. cAMP binds to the regulatory subunits of PKA (Protein Kinase A), activating it.

6. PKA has 2 catalytic subunits and 4 regulatory subunits.

7. The catalytic subunits of PKA dissociate, becoming active.

8. The active PKA subunits phosphorylate target proteins in the cell, regulating their function.