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Transcript
• 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