Biochemistry I Fall Term, 2000

Lecture 25: Biological Membranes

Assigned reading in Campbell: Chapter 6.3-6.6

Take the Review Quiz on Lecture 25 concepts.

Bacteriorhodopsin embedded in a bilayer membrane (156K): a Chime page showing an integral membrane protein.

Different types of lipids — composition varies (type & acyl chain) by organism, tissue type, and for prokaryotes, growth temperature.

Defines cellular topology (i.e. an inside and an outside)

1. Signal transduction occurs across the membrane.
2. Transport of molecules and ions occurs across membranes.
3. Nerve conductance involves membrane potential changes.
4. Generation and maintenance of an electrochemical potential:
   A concentration difference across the membrane can be used to generate free energy. ATP synthesis in the mitochondria utilizes the concentration gradient generated by pumping protons out. The free energy that results due to a concentration difference can be calculated from:
       DG = RTln([in]/[out])
   For example, a concentration difference of 10³ (mM versus mM) corresponds to 17 kJ/mol (4 kcal/mol).

Cholesterol:

• About the same length as C₁₆ fatty acid; therefore it reaches across half of the bilayer.
• Required as a precursor for steroid hormone synthesis.
• Used to make bile acids: a biological 'detergent' used to solubilize fats in the small intestine.
• Essential component of most mammalian membranes.
• Destroys the phase transition of pure lipid membranes, thereby keeping the membranes fluid.
• Synthesized in mammals, where the levels can be elevated by:
    1. High intake.
    2. Genetic deficiencies, e.g. in the LDL carrier protein

Peripheral Membrane Proteins:

• Loosely attached to membranes via electrostatic interactions — released with high salt.
• Often involved in electron transport and, as specific binding proteins, sugar transport in bacteria.

Integral Membrane Proteins:

• Largely contained in the membrane (requires disruption of the membrane by detergents for solubilization).
• Stability energetics are similar to water soluble proteins, except that non-polar groups interact with acyl chains in the membrane. The rule here is: "hydophobic outside--hydrophilic inside", thereby matching the location.
• Usually span the entire membrane.
• Asymmetry is required for most functions:
    1. Cell surface markers
    2. Transport (e.g. of protons, metabolites, electrons)
• Fluid mosaic model (Campbell, Fig. 6.15)

1. Active transport: the Na⁺/K⁺ pump (Campbell, Fig. 6.19)
     ATP is the energy source.
     Stoichiometry is 3 Na⁺ (pumped out):2 K⁺ (pumped in).
2. Membrane receptors: the LDL receptor (Campbell, Fig. 6.21)
     The LDL receptor participates in endocytosis.
     Hormone receptors signal physiological conditions to the cell interior.
3. Bacteriorhodopsin (Not in Campbell)
   
   1. Major membrane protein (~75%) of Halobacter halobium when grown at low levels of O₂ and 4 M NaCl. The "purple membrane" is a two dimensional crystalline array.
   2. Note these features on the Chime page:
      The protein has seven a-helices that span the bilayer.
      The membrane-exposed surface is highly hydrophobic.
      The charged/polar residues are at the solvent interfaces and line the internal hydrophilic channel.
   3. The protein is a light-driven proton pump. Light is absorbed by the retinal pigment, which is bonded to Lys 216. A [H⁺] gradient is generated that is used to synthesize ATP.

Lipid-Linked Proteins:

• S-Farnesyl/geranylgeranyl cysteine methyl ester (anchor and trafficking)
• Myristalization (attached to amino-terminal Glycine)
• Attachment of palmitic acid to Cys.
• GPI (glycosylphosphatidylinositol ) linked.

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