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• Lipids: Precursors to Intracellular messengers
Other lipid functions
PLA2
• Hormones
– Prostaglandins
• Inflammation,
wake/sleep, labor
– Thromboxanes
• Blood clot formation
– Leukotrienes
• Severe allergic
reactions
Steroids: Derivatives of Cholesterol
• More polar than
testosterone: transport
through the blood stream
– Protein-mediated
• Enter cells: regulate gene
expression
– Sex hormones
– Regulate tissue
growth/swelling
– Differentiation
– etc.
Fat soluble vitamins
• Vitamin D (steroid
derivative)
– Regulates Ca+2 levels in
kidney and bone
• Vitamin A
– Retinol
• Visual pigment
– Regulates gene
expression
• epithelial tissue
Fat soluble vitamins
• Vitamin E
– Biological antioxidant
– Destroy oxygen
radicals
– Prevents oxidative
damage to
membrane lipids
(and other
biomolecules)
Fat soluble vitamins
• Vitamin K
– Blood clotting vitamin
– Participates in protein
modification
• Carboxylation of
glutamate: Ca2+ affinity
– Formation of active
prothrombin
• Conversion of
fibrinogen to fibrin
• Fibrin holds the clot
together
g-carboxy
glutamate
Biological membranes
• Define cell boundary
• 1° components
– Lipids
– Proteins
– Carbohydrates
Composition of membranes is variable
Lipid bilayer
• Hydrophobic interior
– Hydrocarbon chains of FAs
– Ring of sterols
– Integral Proteins
• Polar exterior
– Polar head groups of FAs
– Peripheral Proteins
– Sugars
Fluid mosaic model
• Lipid bilayer is dynamic
but stable
– IM Interactions are
constantly changing
• Proteins and lipids can move
laterally
• Rotation about C-C bonds
Asymmetry: inside vs. outside
Different proteins exposed
Different lipids/headgroups
Membrane proteins
• Peripheral
– Globular
– Weakly associated: H-bonds or +/• ‘Easily’ dissociated
• Integral
– Strong association with membrane
• Portion of protein is embedded
a-helical or b-sheet
• Or covalent link to embedded lipid
– Hydrophobic interactions
– What can dissociate?
• Functions?
•
Integral membrane proteins
• Sometimes
hydrophobic alpha
helix through
membrane
– Membrane-spanning
• Interactions with polar
headgroups
• “Membrane topology”
Integral membrane proteins
Multiple membrane-spanning regions:
possibility for hydrophilic core
Membrane dynamics
• Types of motion
– Lateral diffusion
• Moves in same monolayer
• mSecond timescale
• Lipids and proteins
– Flip-flop diffusion
• Uncommon unless catalyzed
(flippase)
• Flippases are very specific
– Membrane lipids synthesis
and transport
– Bacterial plasma
membrane phospholipids
Membrane dynamics
• Degree of fluidity is similar in all membranes
– Cells regulate composition based on growth
conditions
Membrane dynamics
• Experiment on lateral
diffusion
– Attach fluorescent probes to
head group to monitor
– Tag all lipids on outer
membrane
– Bleach the probe
– Measure fluorescence return
Membrane asymmetry
• ‘Rafts’
– Thick, more ordered
microdomains
– Exclude
glycerophospholipids
(shorter sat/unsat chains)
• Glycosphingolipids (long
FA chains…mostly sat)
• Cholesterol
• Integral membrane
proteins