Lipids I

Lipids: The Biomolecule That’s Not a Polymer

  • Divided into 3 categories:

    • Fats (Triglycerides)

    • Glycerophospholipids

    • Steroids (includes cholesterol & steroid hormones)

  • Fats and membrane lipids have fatty acid subunits

Fatty Acids: Building Blocks

  • Composed of carboxylic acids with long hydrocarbon chain

  • HC tail is usually between 12 - 20 C, 

  • Carboxyl group exists in deprotonated form

  • Saturated are able to pack together more closely, and can form more intermolecular bonds, increasing the melting point

Triglycerides

  • 3 fatty acids + glycerol

  • Numbering system of triglyceride comes from 

  • Scientists replace H with deuterium in glycerol to give it higher priority than other CH2OH group

    • Called proS position → becomes sn1 position

    • Results in S configuration

  • Melting point of triglyceride is impacted by fatty acid chains (more saturated chains = higher melting point; more unsaturated chains = lower melting point)

Cell Membranes Contains 3 Types of Lipids

  1. Glycerophospholipids (phospholipids)

  2. Sphingolipids (some sphingolipids are phospholipids)

  3. Cholesterol (sterol)

  • Both glycerophospholipids and sphingolipids utilize fatty acid subunits, but have different backbones

  • All are amphipathic


Glycerophospholipids

  • Built form glycerol-3-phosphate backbone + 2 fatty acids at position 1 and 2 of backbone

    • One is saturated, the other is unsaturated

  • Head group is bound to phosphate at position 3 (can vary)

    • Phosphate + Inositol (PI) carry negative charge

  • Amphipathic

    • Head = hydrophilic; tail = hydrophobic


Sphingolipid

  • Derivative of sphingosine

  • Attachment of fatty acid through amide linkage

  • Head group attaches to hydroxyl of sphingosine

  • Sphingoglycolipids are enriched in lipid rafts (non-covalent interactions between sugar groups of neighboring lipids)

  • Sphingoglycolipids are found in outer leaflet


Cell Membranes Contain Cholesterol

  • Orientation within membrane mirrors orientation of glycerophospholipids and sphingolipids

  • Composed of hydrophobic ring and tail → oriented with / like fatty acid tails

  • Hydroxyl group (polar) → oriented with / like polar head


Lipids Form Organized Structures Spontaneously

  • Lipids are driven to form aggregates to reduce exposure of hydrophobic regions to water (hydrophobic effect)

  • Structure that forms is dependent on the type of lipid

    • Single tailed lipids → form micelles

    • Two tailed lipids → forms lipid bilayers

      • Half of lipid bilayer → leaflet

      • Leaflet pointing toward cytosol → cytosolic face

      • Leaflet pointing away from cytosol → exoplasmic

  • Sheets of lipid bilayers are energetically unfavorable because hydrophobic tails are exposed to water

  • Due to this, it forms a sphere to seal away hydrophobic tails


Composition of Lipids in Membranes Vary

  • Glycolipids are exclusive found on exoplasmic leaflet due to how they are synthesized

    • Due to fact that sugars are added on inside the golgi apparatus

  • Phospholipases

    • Composition of lipids is determine by cleavage of lipids with phospholipases exposed to outside the cell

    • Analysis of composition of each type of lipid before and after enzymatic treatment

  • Phospholipase A cleaves the fatty acid 1

  • Phospholipase C cleaves phosphate and head group

  • Phospholipase D cleaves head group


Membrane Lipids are Fluid Within Leaflet

  • Flip-flopping is promoted by proteins like flipasses/scramblases, and phospholipids translocators

  • Fluidity is promoted by shorter hydrocarbon chains and unsaturated fatty acids (more fluidity)

    • This is due to decreased interactions between fatty acid tails

  • Fluidity restricted by insertion of cholesterol (lipid raft formation = less fluidity)


Lipid Rafts are Specialized Membrane Domains

  • Regions of membrane hypothesized to exhibit less mobility

    • They are envisioned as “rafts” in the “sea” of fluid lipids surrounding it

  • Lipid rafts - specialized domain enriched in sphingoglycolipids, cholesterol, saturated tails (contributes to decreased fluidity)

  • Enriched in proteins → protein-protein interactions → help facilitate formation of lipid raft

  • Enriched in glycolipid → non-covalent interactions between sugars → help facilitate formation of lipid raft

  • Organize proteins that function together


Critical Features of a Cell Membrane

  1. Compartmentalization

  2. Solute Transport

  3. Scaffold for Biochemical Activity

  4. Cell Signaling

  5. Cell Structure

Schematic of Cell Membrane