lipids: precursors to intracellular messengers other lipid functions hormones –prostaglandins...

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Page 1: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot
Page 2: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

• Lipids: Precursors to Intracellular messengers

Page 3: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

Other lipid functions

• Hormones– Prostaglandins

• Inflammation, wake/sleep, labor

– Thromboxanes• Blood clot formation

– Leukotrienes• Severe allergic

reactions

PLA2

Page 4: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

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.

Page 5: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

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

Page 6: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

Fat soluble vitamins

• Vitamin E– Biological antioxidant– Destroy oxygen

radicals– Prevents oxidative

damage to membrane lipids (and other biomolecules)

Page 7: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

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

Page 8: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

Biological membranes• Define cell boundary• 1° components

– Lipids– Proteins– Carbohydrates

Composition of membranes is variable

Page 9: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

• Hydrophobic interior– Hydrocarbon chains of FAs– Ring of sterols– Integral Proteins

• Polar exterior– Polar head groups of FAs– Peripheral Proteins – Sugars

Lipid bilayer

Page 10: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

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

Page 11: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

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?•

Page 12: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

Integral membrane proteins

• Sometimes hydrophobic alpha helix through membrane– Membrane-spanning

• Interactions with polar headgroups

• “Membrane topology”

Page 13: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

Integral membrane proteins

Multiple membrane-spanning regions: possibility for hydrophilic core

Page 14: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

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

Page 15: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

Membrane dynamics

• Degree of fluidity is similar in all membranes– Cells regulate composition based on growth

conditions

Page 16: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

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

Page 17: Lipids: Precursors to Intracellular messengers Other lipid functions Hormones –Prostaglandins Inflammation, wake/sleep, labor –Thromboxanes Blood clot

Membrane asymmetry

• ‘Rafts’– Thick, more ordered

microdomains– Exclude

glycerophospholipids (shorter sat/unsat chains)

• Glycosphingolipids (long FA chains…mostly sat)

• Cholesterol• Integral membrane

proteins