Lipids and Membranes

• Fatty Acids with the least double bonds or kink and bigger length have a higher melting point than short and unsaturated fatty acids
• Membrane lipids are amphipathic with a hydrophilic polar head group and a hydrophobic fatty acid tail. Have mostly negative net charge and form lipid bilayer with polar exterior and hydrophobic core
• 5 Types of membrane lipids

  1. Glycerophospholipids
  2. Sphingolipids
  3. Galactolipids
  4. Ether lipids
  5. Sterol Lipids
• Phospholipids are phosphate containing lipids

  • Glycerophospholipids
  • Sphingolipids like sphingomyelin
• Glycolipids are carbohydrate contianing

  • Sphingolipids like cerebrosides, gangliosides etc
  • Inositol Lipids
  • Galactolipids
• Sulfolipids are sulfur containing lipids
• Glycerophospholipids:

  • Has glycerol-3-phosphate as central core
  • Which is chiral unlike glycerol
• Glycerophospholipid Substituents

  • Has Fatty acids attached via ester linkages to C1 and C2
  • C1 is usually saturated C2 is usually unsaturated chain
  • A polar substituent is attached to phosphate that is attached to C3
• Headgroups on glycerophospholipids can contribute positive or negative charges making the whole lipid neutral or negative
• Phosphatidic Acid is glycerophospholipid with no additional polar headgroup
• Adding Ethanolamine to the phosphate makes the charge neutral and named phosphatidyl ethanolamine
• Adding water to phosphate of glycerophospholipids makes the charge -1 or -2 and called phosphatidic acid
• Adding Choline to the phosphate makes charge neutral and called phosphatidyl choline
• Adding serine to phosphate of glycerophospholipid makes charge -1 ad called phosphatidyl serine
• Adding Myo-inositol to phosphate of glycerophospholipids makes charge -1 and called phosphatidyl inositol
• Adding Glycerol to phosphate of glycerophospholipid makes charge -1 and called phosphatidyl glycerol
• Adding phosphatidylglycerol to phosphate of glycerophospholipids makes charge -2 and callign diphosphatidyl glycerol
• Phosphatidylinositiol-4,5-Bisphosphte is glycerolphospholipid with average charge of -4 at pH of 7.0 because it has two phosphate groups attached to sugar that have 2 negative charges each
• Phospholipase: can degrade specific glycerophospholipids has Type-A, Type-C and Type-D
• Type-A phospholipase is a hydrolase that cleaves acyl groups yeilding fatty acid and alcohol. Can cut C1 or C2
• Type-C and Type-D phospholipase cleaves polar headgroup on ither side of phosphate group at C-3
• Type-A1 phospholipase cleaves at C1 so removes Saturated fatty acid side
• Type-A2 cleaves C2 so removes unsaturated fatty acid chains
• Sphingolipids:

  • Have Sphingosine backbones synthesized from serine and palmitate
  • Is a single fatty acyl chain attached via amid bond
  • Has variable polar head group that determines class of sphingolipid
• Sphingolipid Structure:

  • Contains a polar region resembling glycerol with an amino acid group
  • Contains a non polar region
  • Has variable polar group attached to C1
  • Sphingomyelin
  • Cerebrosides
  • Globosides
  • Gangliosides
• Gangliosides contain various derivatives of galactose in linear line with steric acid and sphingosine as well as N-acetylneuraminidate or sialic acid. Negative charged due to carboxyl group
• Galactolipids or sulfolipids are:

  • Common in plant cells
  • do no require phosphate
  • Sulfonates can carry negative charges like phosphate
  • Galactolipids have 1 or two galatcose units at C3 and 2 acyl chains one at C1 and one at C2
  • Unsaturated fatty acids
• Archae membrane lipids:

  • Can have ether-linked that are more resistant to hydrolysis during heat or low pH
  • Have phospholipids
  • Have branched isoprenoid chains
• Sterols are:

  • Rigid membrane lipids with fused ring structure
  • Cholesterol is an example
  • Length similar to 16:0 fatty acyl group
• Lipids can be signalling molecules like hormones or involved in reactions like cofactors
• Membrane proteins are:

  • Flexible and self sealing
  • Thin to enhance reaction rates and because it is small
  • Selectively permeable for transport and signalling limit
  • Form due to hydrophobic effect
• Bilayers are fluid like:

  • Lipids orientate themselves based on distribution of hydrophobic and hydrophilic character
  • Can diffuse laterally (across) rapidly due to non-covalent ineractions
• Phase transitions:

  • Can have temperature dependent transition that affect motion of lipids
  • Increase temperature makes more disordered
  • Maintains fluidity by altering membrane lipids to keep membrane in liquid ordered state
• Membrane Assymetry:

  • glycoproteins or glycolipids have carbohydrate aspect facing exterior to cell or plasma membrane
  • Different leaflets have different compositions
  • Appearance of specific lipids can trigger special events
• Synthesis of lipids carried out by integral membrane proteins in the ER in eukaryotes
• Lipids distribute asymmetrically in membrane as different cells need different strength:

  • Find Sm and PC in outerleaflet mostly
  • Find PE in mostly inner leaflet
  • Find PS only in inner leaflet
• Movement of lipids from one leaflet to another is extremely slow in bilayers but rapid in membranes
• Flippases move PS and PE into the membrane. Is ATP-dependent and form of primary active transporters
• Floppases move things out like PC and Sphinoglipids. Is ATP-dependent and a form of primary active transporters
• Passive transport equalizes concentrations between leaflets and can use scamblases to remove asymmetry