Lipid Membranes & Cells Flashcards
What is the overall function of lipids?
Lipids are the way that life make cells and compartments (organelles)
What are the roles of lipids?
Lipids come together to form membranes
- provide structure
- allow selective transport
- inform communication between cells
- allow electrical conductance
- facilitate control mechanism
What part of cells are a major drug target?
Membrane proteins are a major drug target
This is because although they are outside of the cell, they stimulate chemistry within
What is a lipid?
They have both hydrophobic and hydrophilic character
Soluble in organic solvents and not so soluble in water
Hydrophobic greasy tail
Polar head group which is hydrophilic- water soluble
What are examples of lipids?
Fatty acyl waters (phospholipids, glycolpids)
Steroids (cholesterol)
Waxes
What are fatty acids?
They form fatty acyl esters Hydrocarbon chains of varying lengths They can have different degrees of saturation - no double bonds= saturated - double bonds = unsaturated
What are membrane lipids?
These are phospholipids
They are abundant in all biological membranes
What do phospholipids contain?
1) fatty acid
2) glycerol
3) phosphate
4) charged, polarised hydrophilic
How do chemistry synthesise ester bonds?
1) add SoCl2 to change OH to Cl as Cl- is a better leaving group than water
- react with an alcohol to form an ester
(See mechanism)
How does nature synthesise ester bonds?
It has Sc-OA ( acyl CoA) as it’s leaving group- good
React with alcohol
( see mechanism)
Sc-OA is natures good leaving group
What are the two ways phospholipids can aggregate?
If there is 1 acyl chain- it forms a lipid micelle
If there are two acyl chains- it forms a phospholipid bilayer (most energetically favourable)
What are the driving forces for bilayer formation?
(Self assembly in water)
1) hydrophobic effect- buried acyl chains (hydrophobic)
2) van der waals interactions between acyl chains
3) polar head groups interact with water
- electrostatic and hydrogen bonding
What are membrane proteins?
Responsible for dynomic processes in membranes
How do integral and peripheral proteins interact?
Integral proteins interact extensively with lipid hydrocarbons
Peripheral interact with hydrogen bonding and electrostatic interactions
What is the fluid mosaic model?
The membrane is a fluid mosaic of proteins floating in a sea of lipids
Lipids can laterally diffuse within the membrane- so can proteins
What does the fluid mosaic model contain?
Phospholipid bilayer
Intergalactic membrane protein
Cholesterol
Peripheral membrane protein
What are examples of integral membrane proteins?
7 alpha helical bundle
Rhodopsin
Porins
Beta barrel
What are the role of glycolipids?
Place sugars external
Allow communication within cell
Assymetric within a memebrane
Describe the structure and position in the membrane of cholesterol
Polar head group and hydrophobic carbon tail
Steroid (25% of the membrane)
Sits within the membrane
Hydrophobic rail is embedded and has van der waals with other chains
Polar head forms H bonds to other phospholipid head groups
Describe the role of cholesterol
Modulates membrane fluidity by disrupting the packing of lipids
Inert into bilayer and causes less regular interactions between phospholipids which causes fluidity
What other parts of the membrane control fluidity
Unsaturated fatty acyl chains also make membrane more fluid
They prevent membrane rigidity which is important at low temperatures
What is a LDL?
A low density lipoprotein (with cholesterol)
Transfers lipids around the body
Linked with atherosclerosis which is the thickening of arteries
High cholesterol causes heart disease
How is cholesterol made?
Acetyl CoA to melvanoate (mediated by HmGCoA reductase) to squalene to cholesterol
Describe the role of membrane drug targets
They are G protein coupled receptors GPCRs
Cell surface receptors
They transmit messages across the membrane (light, peptide, lipids or sugars)
Roles in vision, mood behaviour and smell
Sense molecule outside the cell- activates a signal transduction pathway
How do beta1 and beta 2 ad renege in receptors act as drug targets?
Beta 1 receptor heart- controls cardiac output
Beta 2 receptor- lungs, controls muscle relaxation in lungs
What is an antagonist and an agonist?
Antagonist is a receptor inhibitor
Agonist is a receptor activator