Biochemistry I Fall Term, 2004 November 3, 2004

Lecture 24: Biological Membranes

Assigned reading in Campbell: Chapter 7.3-7.5

Key Terms:

Integral membrane protein Electrochemical potential

Peripheral membrane protein ∆G = RTln([in]/[out])

Cholesterol ∆G = ZAF∆Ψ

Fluid mosaic model Receptor proteins

Links:
(I) Review Quiz on Lecture 24 concepts
(I) Membranes: Flash tutorial and key features
(S) Examples of integral membrane proteins on Chime pages:
Bacteriorhodopsin Maltoporin Hemolysin.

Overview of Biological Membranes

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).
Phospholipid bilayers are impermeable to molecules or ions without protein transporters.

1. Transport of molecules and ions occurs across membranes.

2. Signal transduction occurs across the membrane.

3. Nerve conductance involves membrane potential changes.

4. Generation and maintenance of an electrochemical potential

Membrane Energetics

1. 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:
∆G = RTln([in]/[out])
For example, a concentration difference of 103 (mM versus µM) corresponds to 17 kJ/mol.

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 2. The unequal distribution of ions across cellular membranes results in an electric
potential difference. Typically, the voltage difference is about -100 mV inside. The free energy
available from the membrane potential for transport of ions is calculated from:

∆G = ZAF∆Ψ
where ZA, is the charge on A; F is the Farraday constant, 96.5 kJ/volt-mol; and ∆Ψ is the
membrane potential.

Consequently, if a charged molecule or an ion (A) is transported into the cell, we must
consider both the chemical and the electrical work required. At equilibrium, the electrochemical
potential of A is

∆G = RT1n([A]in/[A]out) + ZAF∆Ψ

Cholesterol

HO

• 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 steep phase transition of pure lipid membranes, thereby keeping the
membranes fluid.

• Synthesized in mammals, where the levels can be elevated by:

• High intake.

• 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.

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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. Surface residues are more hydrophobic
than the hydrophobic core.

• Usually span the entire membrane.

• Asymmetry is required for most functions:

Cell surface markers

Transport (e.g. of protons, metabolites, electrons)

• Fluid mosaic model (Campbell, Fig. 7.18)

Examples of Membrane Protein Structures and Functions

1. Membrane receptors: the LDL receptor (Campbell, Fig. 7.27)

The LDL receptor participates in endocytosis.

Hormone receptors signal physiological conditions to the cell interior.

2. Three examples of integral membrane proteins on Chime pages (Not in Campbell):

Note some of these features in common:

a) All have hydrophobic surfaces exposed to the bilayer.
b) Lateral motion in the bilayer plane occurs, but not "flip-flop" across.
c) Glycosylation occurs at residues on the outside surface
d) Most have two "girdles" of Trp residues at the inner and outer leaflet surfaces.

Bacteriorhodopsin

a. The protein has seven α-helices that span the bilayer.

b.The charged/polar residues are at the solvent interfaces and line the internal
hydrophilic channel.

Maltoporin

a. This trimeric bacterial protein has 18 β-strands in each β-barrel spanning the
bilayer.
b. Several aromatic side chains line the sugar binding site.

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 Hemolysin

a. Another all β-protein made up of seven subunits that assemble in the

membrane.
b. The 15 Å pore created in red blood cell membranes accounts for the cytolytic
properties of this bacterial toxin.

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.

10.18.04