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: Ca 2+ affinity –Formation of active prothrombin Conversion of fibrinogen to fibrin Fibrin holds the clot together  -carboxy glutamate

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 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  -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