Lipids Flashcards
Describe 3 broad areas for lipid functions and provide examples
The biological function of lipids
- Storage
- Structural
- Signals
Functional Classification of lipid
1. Storage lipid
- Fatty acids, triacylglycerol, waxes
2. Membrane lipids
- Phospholipids, glycolipids, cholesterol
3. Signalling and cofactor lipids (present in smaller quantities)
- Phospholipid derivatives (inositol phospholipids)
- Steroid hormones (cholesterol derivatives)
- Eicosanoids (paracrine hormones e.g. prostaglandins)
- Lipid soluble vitamins (vitamin A)
Role of lipids in the properties of cell membranes
1. Animal cell
- surrounded by a plasma membrane
- Within the animal cell, there are a number of membrane bound organelles that compartmentalise the cell providing the environments for different biological functions
- Plant cell
- Surrounded by a cell wall that has structural integrity because it has a large carbohydrate component
Define the term “lipid” and be able to distinguish lipids from other major classes of biological molecules
Functional definition of lipids
> Biological lipids:
- A chemically diverse group of compounds that play an equally diverse set of functions in the cell
- Are compounds that generally have non-polar properties (entirely or in part) and are therefore characterised by their low solubility in water
- Can be subclassified into functional groupings:
- Abundant
* Energy storage
* Structural (components of biological membranes)
- Lower concentrations of these in cells
* Signals and cofactors
Name saturated and unsaturated fatty acids
Fatty Acids:
- Carboxylic acids with hydrocarbon chains containing between 4-36 carbons
o Almost all natural fatty acids have an even number of carbons
o Most natural fatty acids are unbranched
- Saturated: no double bonds
- Monosaturated: one double bond between carbons in the alkyl chain
- Polyunsaturated: more than one double bond in the alkyl chain
Fatty Acid Nomenclature:
- Fatty acids:
o Are hydrocarbon derivatives
o Contain 1 carboxylic acid group (at physiological pH, charge = -1)
o + hydrocarbon chain (4-36 carbons are common)
- Short hand nomenclature eg. 18:0 means 18 C and 0 C=C
Draw fatty acids from their name
Yes
Predict and explain trends in fatty acid melting temperatures and solubilities
Conformation of Fatty Acids:
> Saturated fatty acid can pack into stable aggregates
- The fully saturated C backbone is usually in a fully extended conformation
- Saturated fatty acids can therefore pack into a nearry crystalline array, stabilised by extensive hydrophobic interactions of the hydrocarbon chain
> Trends of physical properties
- Longer carbon chains require more energy to disrupt the packing
- Higher melting temperatures
> Unsaturated fatty acids
- = 1 carboxylic acid group (-1 charge at physiological pH)
- + hydrocarbon chain containing 1 or more double bonds
- Unsaturated CIS fatty acids pack less orderly due to the kink
- less-extensive favourable interactions
- It takes less thermal energy to disrupt disordered packing of saturated fatty acids
- Unsaturated CIS fatty acids have a lower melting point
> Trans fatty acids
- Trans fatty acids form by partial dehydrogenation of unsaturated fatty acids
- Done to increase shelf life or stability at high temperature of oils used in cooking (especially deep frying)
- A Trans double bond allows a given fatty acid to adopt an extended conformation
- Trans fatty acids can pack more regularly and show higher melting points than cis forms
- Consuming trans fats increases risk of cardiovascular disease
Avoid deep frying partially hydrogenated vegetable oils
Current trend: reduce trans fats in foods
Explain trends in melting temperatures of natural fats
Solubility and Melting Point of Fatty Acids
- Solubility in Water
o Decreases as the chain length increases
- Melting point
o Decreases as the chain length decreases
o Decreases as the number of double bonds increases
Identify omega-3 and omega-6 fatty acids
Omega-3 fatty acids are essential nutrients
- Humans need them but cannot synthesise them
- They include ALA, DHA, and EPA
o Although DHA and EPA can be synthesised from ALA
o ALA = alpha-linoleic acid
o DHA = docosahexaenoic acid
o ONLY NEED TO KNOW HOW TO USE SHORT HAND NOMENCLATURE
Draw molecular and schematic representations of triacylglycerols, name the different molecular groups within these lipids, and explain how these molecular groups contribute to the properties of these lipids
Storage Lipids (Fatty Acids & Triacylglycerols)
- Triacylglycerols (=triglycerides, fats)
o = fatty acid esters of glycerol
- 3 OH of glycerol provide the 3 sites for fatty acid linkage
- Simple = all 3 fatty acids identical (e.g. tristearin, triolein, tripalmitin)
- Mixed = fatty acids differ (as shown)
- HYDROPHOBIC
- Triacylglycerols
- provide stored energy and insulaton
- Higher energy yield than oxidation of other fuel sources such as glycogen or starch
- Not hydrated (less weight)
Triacylglycerol composition:
- 1 glycerol backbone
- 3 fatty acid chains
- Each fatty acid is linked to the glycerol (3 OH sites) by ester bonds (condensation reaction)
Explain the differences between the major structural lipids – glycerophospholipids, sphingolipids and glycolipids.
Membrane lipids –
- Biological membranes are a double layer of lipids (Lipid bilayer) with a hydrophobic core, acting as a barrier to the passage of polar molecules and ions
Phospholipids
- Are defined by the phosphate group within their polar head group
- Can be drawn by analogy with the triacylglycerols
- (but 3 non-polar tails)
- Can be further classified by their chemical components
- Glycerophospholipids (based on the glycerol molecules)
- Sphingolipids (sphingophospholipids) (based on sphingosine)
- The most common glycerophospholipid is phosphatidylcholine
Concept map:
> Phospholipids
1. Glycerphospholipids (important structural/signalling lipids)
- The most common glycerophospholipid is phosphatidylcholine
- Glycerol backbone
- Two fatty acid chains
- One phosphate-alchohol group
- simplest example is phosphatidic acid
- the charge of each glycerophospholipid will depend on the identity of the head group
- sphingolipids
- sphingosine backbone
- two fatty acid chains (sphingosine contributes one of the two fatty acid chains)
- one phosphate-choline group
- the simplest example is ceramide
> Glycolipids
- As components of the outer membrane leaflet, can contribute to sites of biological recognition, as seen for the use of glycosphingolipids as determinants of the blood groups A, B and O
- contain mono or oligosaccharide units in their head groups
> Sterols
Draw schematic representations of membrane lipids and name the different molecular groups within these lipids.
Yes
Explain how sterols (e.g. cholesterol) are described as amphipathic molecules
Sterols
- have 4 fused carbon rings (3 rings are 6C rings and 1 ring is a 5C ring)
- the fused ring structure constrains their conformation
- almost planar and relatively rigid
> Example: cholesterol
- the main sterol in animal tissues
- has both hydrophilic and hydrophobic characteristics - AMPHIPATHIC
- In addition to structural roles in membranes, cholesterol plays important roles in signalling acting as a precursor for steroid hormones
Draw an annotated schematic diagram of the fluid mosaic model - describe organisation of lipids in an aqueous environment (micelles, bilayers, liposomes)
Biological membrane are Phospholipid Bilayers
- The fluid mosaic model of membranes incorporates proteins within the lipid bilayer:
- Proteins embedded in the bilayer sheet are held by hydrophobic interactions
- The interactions among the components are NONcovalent (allowing fluid, dynamic properties)
- Charges of the lipid head groups contribute significantly to surface properties of membranes
Yes - refer to diagram
- Amphipathic molecules in aqueous environments favour packing that keeps their hydrophobic regions together and orients their hydrophilic regions together the polar water environment
- Shape (cross section of head group relative to side chain determines the packing arrangments:
- Fatty acids form MICELLES
- Phospholipids form BILAYERS
Micelles:
- hydrophobic regions are buried in the cores of these structures
- individual units are wedge-shaped (cross-section of head greater then that of side chain)
Bilayers:
- individual units are cylindrical (cross-section of head equals that of side chain)
Bilayer conversion to liposome:
- hydrophobic regions of bilayer are exposed to water. Unstable
- Bilayers fold back on self to form a hollow vesicle (liposome)
- continuous bilayer formed
- phospholipid bilayer with aqueous cavity
Define the differences between lateral diffusion and transbilayer translocations and describe how these might be measured experimentally
- Lateral Diffusion in Membranes:
- Membrane lipids (and membrane proteins) diffuse laterally in each leaflet of the membrane lipid bilayer structure, i.e. they stay within the plane of the leaflet and exchange places with their immediate neighbours
- Lateral diffusion can be measured experimentally by Fluorescence Recovery After Photobleaching (FRAP) experiments
FRAP:
- react cell with fluorescent probe to label lipids
- intense laser beam bleaches small area
- over time, unbleached phospholipids diffuse into the bleached area (Measure the rate of fluorescence return)
- Transverse diffusion/transbilayer translocation (flip flop)
- very slow
- the lipid moves from outer leaflet (membrane facing ECM) to the leaflet
- Catalysis (use of specialised proteins embedded in bilayer to facilitate transbilayer movement of lipids) provide a path that is energeticall more favourable and faster than uncatalysed movement
> Flippases
- moves from outer to cytosolic leaflet
> Floppases
- Move phopspholipids from cytosolic to outer leaflet
> Scramblases
- move lipids in either direction, toward equilibrium
Describe how temperature and composition impact on membrane fluidity
The fluidity of a membrane depends on its composition:
- Depends on what types of fatty acids are present
- How long the chains are and their degree of unsaturation
o The more saturated the fatty acids are the better they will pack and the more rigid they will be
o The higher the content of unsaturated fatty acids in the tails, the more fluid the membrane will be due to disruptions of the packing
- Cholesterol content
o At low concentrations, cholesterol breaks up the packing and causes membranes to be more fluid
o At high concentrations, it stiffens the membrane, as cholesterol molecules pack against each other
Temperature
- Phase transition temp: temp at which membrane goes from paracrystalline structure to fluid state
- At 37C all biological membranes are in fluid state
Describe the asymmetry of biological membranes
Chemical analysis of biological membranes shows an assymetry of distributions of proteins and lipids between te two membrane leaflets
- membranes show “sidedness”
Explain how membrane rafts form
> Membrane rafts are modifiers of membrane fluidity
- Sterols (cholesterol) can prevent phospholipid packing, but has rigidity to facilitate packing themselves –> there conc’s will thus modulate membrane fluidity
- Sterols and sphingolipids cluster together in “membrane rafts” (also called lipids rafts/microdomains)
- They are thick, more ordered and harder to dissolve
- behave like a liquid-ordered RAFT in the SEA of liquid-disordered phosphilipids
- Lipid rafts remain in non-ionic detergents which will dissolve the rest of the membrane
List the roles of membrane proteins
What roles do membrane proteins play?
- Permit selective entry and exit of molecules from cell (e.g. via transporters)
- Provide recognition signals (e.g. receptors for growth factors)
- Provide structural support to the cell
Compare the properties of peripheral and integral membrane proteins
Behaviour of proteins in membranes:
- Most membrane proteins are free to diffuse laterally in lipid matrix
- How do proteins interact with the membrane?
o Integral membrane protein
o Peripheral protein
Integral membrane proteins are firmly attached (a b and c)
Peripheral membrane proteins associate with outside surfaces (d and e)
Peripheral membrane proteins associate with membranes by:
- Ionic interactions and H-bonding with:
o Polar head groups of lipids
o Integral membrane proteins
- Released from membranes by reagents that disrupt ionic interactions:
o High salt
o Change pH
o Chelating agent
Integral membrane proteins interact with membranes by:
- Hydrophobic interactions with:
o Acyl chains of membrane lipids
- Released from membrane by reagents that disrupt hydrophobic interaction:
o E.g. detergents (such as SDS – sodium dodecyl sulphate)
Describe how peripheral and integral membrane proteins can be experimentally released from biological membranes
All membrane proteins have a unique orientation in the membrane
- How can we determine the orientation/arrangement of membrane proteins?
o Protease sensitivity of proteins from intact cells
Treating the proteins with an enzyme that breaks it up to determine the parts of the protein that are exposed to the protease and which aren’t
Protease sensitivity (determining trypsin sensitivity)
- trypsin cleaves on the carbonyl side of lysine and arginine but only has access to the outside party of the protein of an intact cell
- analysis of remaining protein after trypsin digestion of cells identifies the domain of the protein buried in the bilayer and/or exposed on the inner surface
Analyze hydropathy index plots to predict numbers of typical membrane helices in a membrane protein
Predicting membrane spanning domains (transmembrane domains)
- membrane is ~3nm thick
- alpha-helix
- 3.6 residues/turn of a helix
- each turn of helix spans
0.54nm in length
- 0.15nm/residue
- ~ 20 hydrophobic residues
to span a 3nm membrane
- A hydropathy index is a number assigned to each amino acid that reflects its tendency to interact with water (or its hydrophobicity or hydrophilicity)
o It quantifies how much an amino acid side chain prefers to be in a watery environment vs a non-watery environment
o It reflects the free energy change required to move from an organic solvent to water - If the hydropathy index is negative value – indicates it’s a favourable conversion
- If the hydropathy index is positive value – indicates it’s an unfavourable/non-spontaneous conversion – the amino acid will want to remain in the organic phase and not move into the water
Explain the differences and similarities between active and passive transport across a biological membrane
- Transport proteins in membranes are responsible for transferring small water-soluble molecules across the lipid bilayer
o Artificial lipid bilayers are impermeable to most water-soluble molecules
o Each transport protein transfers a particular type of molecule (eg. Specific) - Membrane transport proteins can be divided into two classes ~ carriers (transporters) and channels
- ONLY NEED TO KNOW CARRIERS
Provide an example of an active transporter and a passive transporter, describing their mechanism of action
- Glucose transporter GLUT1 is a passive transporter
- Nearly all mammalian cells use glucose as major source of energy
- GLUT1 Is a transporter found in membranes of many cells
- GLUT1 facilitates passive transport (facilitated diffusion) of glucose down a concentration gradient
- No other substance transported
- Glucose transporters exists in two conformations (T1 and T2)
- binding of glucose (from blood plasma) may induce a conformation change from T1 to T2
- explains net transport of solute down its conc gradient - Active transporters
- Transport of solutes against a concentration gradient
- Requires energy input
- One class of membrane proteins that uses ATP hydrolysis to pump ions across membranes are the ubiquitous P-type ATPases
> examples:
- Na+/K+ ATPase (pumps Na+ out, K+ in cell)
- H+/K+ ATPase (pumps H+ out, K+ in (acidifies stomach))
- Ca2+ ATPase (pumps Ca2+ out of cytosol)
Main example:
1. P-type ATPases
- transporter binds 3Na_ from the inside of the cell
- phosphorylation favours P-enz
- Transporter releases 3 Na+ to opposite and binds 2K+ from the outside of the cell
- dephosphorylation favours Wnz
- transporter releases 2K+ to inside
> Na+K+ ATPase-function
- Na and K gradient in animal cells is important to maintain cell volume and create transmembrane electrical potential
