Biochemistry: A Short Course

1
Phospholipids and Glycolipids Self-Assemble to
Form a Lipid Bilayer

• Driving Forces
• H-bonding
• Hydrophobic effect
• Electrostatic interactions
• Van der Waals attractions (close packing)

2
Membrane Fluidity Temperature, Cholesterol and
Fatty-Acid-Composition Regulated
How does membrane composition alter with elevated
temperature?
3
Significant Lateral Albeit Minimal Transverse
Lipid Movement
4
Liposome for Potential Drug Delivery
5
Peripheral and Integral Proteins
Different membrane orientation (a and e),
surface position (f and e) and membrane
componentassociation (d and e)
What tethers peripheral proteins to the
membrane? What secondary structure is common in
membrane hydrophobic regions?
6
Hydropathy Plots Identify Potential
Trans-Membrane Peptide Regions
Hydrophobicity Index the free energy needed to
transfer
successive segments of a polypeptide from
a non-polar solvent to water
Hydropathy Plot
7
Alpha Helices Compose the Integral Protein
Bacteriorhodopsin
Bacteria light-harvesting protein that generates
proton gradient a-Helix most common 2
membrane structure Helical (yellow) and charged
(red)residues
8
Bacterial Channel - Porin
Beta barrel with a hydrophobic exterior and a
hydrophilic core Hydrophobic (yellow) and
hydrophobic (white) residues shown
9
Partially-Embedded Prostaglandin Synthase
Converts arachi-donic acid (204) to
prostaglandin H2
10
Aspirin Blocks Prostaglandin Synthase Hydrophobic
Channel
Prostaglandin stimulates inflammation responses
and reduces gastric acid secretion
11
Sodium Gradient Formed via a Na-K ATPase
Antiport Pump

• P-type ATPases form a phosphorylaspartate and
  include
• Ca2 ATPases for muscle contraction
• Gastric H-K ATPases

Link
http//highered.mcgraw-hill.com/sites/0072495855/s
tudent_view0/chapter2/animation__how_the_sodium_po
tassium_pump_works.html
12
Secondary Transport via a Common Sodium
Concentration Gradient

• Na-K ATPase antiporter gradient drives
• Glucose import via a Na- glucose symporter
• Calcium ion export
• via a Na-Ca2
• antiporter

13
Digoxin Na-K Pump Inhibition via
Dephosphorylation Blocking
Digoxin a cardiotonic steroid medication used
for atrial fluttering and heart failure.
How can digoxin be chemically described?
Digitalis purpurea
14
Motor Protein
Actin interacts with the thick filament of myosin
causing muscle contraction
Thick Filament
15
Myosin Head and Neck Region
16
Myosin-Actin Reaction Cycle
17
Ca2 Allows for Myosin-Actin Binding
Actin
How does digoxin affect muscle contraction?
Actin
18
Digoxin Na-K Pump Inhibition via
Dephosphorylation Blocking
Calcium ion export via a Na-Ca2 antiporter
How does digoxin affect Ca2 abundance?
Digitalis purpurea
19
Size Selective Channel Only Allows Potassium Ion
Passage

• K movement
• Down the concentration gradient
• From cytosol to cell exterior

Cell exterior
Cytosol
20
Selectivity Filter Determines the Preference of
K Over Other Ions
Two of four trans-membrane alpha helices
shown Dehydrated K ions move across the
membrane Ionic diameter K 2.66 Å and Na
1.9 Å
Why does Na not move through this pore?
21
Energetic Basis of Ion Selectivity
K energy balance Dehydration versus Carbonyl
oxygen resolvation in selectivity-filter lining
Does tight K binding slow transport across the
channel?
22
Electrostatic Repulsion Forces Pushes and Speeds
K Through Ion Channel

• Selectivity filter contains 4 binding sites
• Ions move down the concentration gradient

23
Na Channel Blocker
Specific in blocking Na while having no effect
on K Reversible binding hydrated Na (nsec),
tetrodotoxin (0.3 min) Lethal dose in humans
10 ng
How does this cork-like toxin position itself?
Host-toxicity prevention mechanism?
24
Chapter 11 Problems 1, 2, 3, 4, 5, 6, 8, 9, 10,
11, 12, 13, and 17