lipids: precursors to intracellular messengers other lipid functions hormones –prostaglandins...
TRANSCRIPT
• Lipids: Precursors to Intracellular messengers
Other lipid functions
• Hormones– Prostaglandins
• Inflammation, wake/sleep, labor
– Thromboxanes• Blood clot formation
– Leukotrienes• Severe allergic
reactions
PLA2
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
-carboxyglutamate
Biological membranes• Define cell boundary• 1° components
– Lipids– Proteins– Carbohydrates
Composition of membranes is variable
• Hydrophobic interior– Hydrocarbon chains of FAs– Ring of sterols– Integral Proteins
• Polar exterior– Polar head groups of FAs– Peripheral Proteins – Sugars
Lipid bilayer
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 exposedDifferent lipids/headgroups
Membrane proteins• Peripheral
– Globular– Weakly associated: H-bonds or +/-
• ‘Easily’ dissociated
• Integral– Strong association with membrane
• Portion of protein is embedded-helical or -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• Second 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