1.4 Lipids and Carbohydrates Flashcards
What are the three broad functions of lipids in biology?
- Storage
- Structural
- Signals
What specific lipids are the storage lipids?
Fatty acids
Triacylglycerol
Waxes
What specific lipids are the membrane lipids?
Phospholipids
Glycolipids
Cholesterol
What specific lipids are the signalling and cofactor lipids?
- Phospholipid derivatives (inositol phospholipids)
- Steroid hormones (cholesterol derivatives)
- Eicosanoids (paracrine hormones eg. prostaglandins)
- Lipid soluble vitamins (vitamin A)
What defines a fatty acid?
Carboxylic acids with hydrocarbon chains containing between 4 to 36 carbons. Usually even number of carbons and unbranched naturally
Types of fatty acids
What is the trend seen with increasing length of the carbon backbone of fatty acids for melting point and solubility in water?
Melting point increases and solubility decreases
How are saturated fatty acids able to pack more closely?
- The fully saturated C backbone is usually in a fully extended conformation
- Saturated fatty acids can therefore pack into a nearly crystalline array, stabilised by extensive hydrophobic interactions of the hydrocarbon chain
How are the dobule bonds usually found in unsaturated fatty acids?
The double bond is usually in the cis form and is usually NOT conjugated
How is the double bond affected by unsaturated fatty acids?
- 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 unsaturated fatty acids so they have a lower melting point
What is the difference between simple and mixed fatty acids?
Simple = all three fatty acids are identical (triolein, tripalmitin)
Mixed = fatty acids differ
Why are fatty acids advantageous as storage lipids?
- Higher energy yield than oxidation of other fuel sources such as glycogen or starch
- Not hydrated so they weigh less
When drawing a model of the fluid mosaic model what components should you include?
- Glycolipid
- Oligosaccharide
- GPI anchored protein
- Sterol
- Integral protein
- Phospholipid
- Sphingolipid
- Peripheral protein
- Peripheral protein covalently linked to lipid
How can phospholipids be further classed?
Glycerophospholipids are based on the glycerol molecule
Sphingolipids are based on sphingosine
Each has a polar head group and two non polar tails
What is the most common glycerophospholipid and its structure?
Phosphatidylcholine
What is the simplest example of a glycerophospholipid?
Phosphatidic acid where X = H
What is the simplest example of a sphingolipid?
Ceramide where X of the alcohol = H
How else can the structure of sphingolipids be changed apart from this?
What is the role of sphingolipids?
They perform distinctive structural and signalling roles (not simply redundant with phospholipids)
How can glycolipids contribute to recognition?
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
What is the structure of sterols?
- Have 4 fused carbon rings (A, B & C = 6 carbon rings, D = 5 carbon ring)
- The fused ring structure constrains their conformation
- almost planar and relatively rigid
What is the role of cholesterol?
- Structural role in membranes
- Role in signalling acting as a precursor for steroid hormones
What shapes do fatty acids with one tail form vs those with two tails?
What shapes do fatty acids form vs phospholipid bilayers?
Fatty acids form MICELLES
Phospholipids form BILAYERS
How does a bilayer convert to a liposome?
- Hydrophobic regions at the edges of the bilayer are exposed to water and therefore unstable
- Bilayers fold back on itself to form a hollow vesicle
- Continuous bilayer with aqueous cavity
What factors influence the fluidity of the membrane?
- Fatty acid composition
- Length of fatty acyl chains
- Degree of unsaturation
- More unsaturated more fluid
- Cholesterol content
- moderates membrane fluidity
- Low cholesterol breaks up the packing making it more fluid
What happens to the lipid bilyaer as temperature increases?
There is a phase transition temperature
- Temperature at which the membrane goes from paracrystalline state to fluid state
- At 37o all biological membranes are fluid
What are the two types of lipid movement in membranes?
How can lateral diffusion be measured?
Experimentally by Fluorescence Recovery After Photobleaching FRAP experiments
How does the flip flop lipid movement occur?
- It occurs very slowly if at all
- Catalysis is essential
- Use of specialised proteins embedded in the bilayer providing an energetically favourable path that is faster than uncatalysed movement
Is the lipid composition the same on the inside and outide of the lipid bilayer?
- No there is an asymmetry
- The exact composition dictates the packing of the lipids within each membrane leaflet
- Spontaneous flip flop is not favoured
What is seen to be a marker of cell death in the lipid bilayer?
Phosphatidylserine is usually found on the inner monolayer of the cell membrane so disruption which exposes the inside contents to the outside suggests there are dead cells
What are membrane rafts?
Where sterols and sphingolipids cluster together in microdomains of the membrane
What roles do membrane proteins play?
- Permit selective entry and exit of molecules from cell via transporters
- Provide recognitions signals. eg receptors for growth factors
- Provide structural support to the cell
What are the two types of proteins that interact with the membrane?
- Intergral membrane protein
- Peripheral protein
How do peripheral membrane proteins associate with membranes?
Ionic interactions and H bonding with:
- Polar head groups of lipids
- Integral membrane proteins
How do integral membrane proteins interact with the membrane?
Hydrophobic interactions with acyl chains of membrane lipids
How are peripheral membrane proteins released from the membrane?
By reagants that disrupt ionic interactions
- high salt
- change of pH
- Chelating agent
How are integral membrane proteins released from the membrane?
By reagants that disrupt hydrophobic interactions
eg detergents such as SDS - sodium dodecyl sulphate
How can we determine the arrangement of membrane proteins?
Protease sensitivity of proteins from intact cells
How can protease be used to determine trypsin sensitivity?
- Trypsin cleaves on the carbonyl side of lysine and arginine but only has access to the outside part of the protein
- After trypsin digestion analysis of remaining protein identifies the domains of protein buried in the bilayer or exposed on the inner surface
How can we predict that there will be a transmembrane protein domain based on the sequence?
We look at if there is hydrophobic amino acids in the sequence with alpha helix conformation and if this spans the width of the membrane (20 amino acids)
WHat does the hydropathy index tell us about an amino acid?
It is a measure of the polarity of each amino acid.
The free energy change required to move from an organic solvent to water.
What does a positive hydropathy value indicate?
It is hydrophobic if it is a positive value
What are the two classes of membrane transport proteins?
Carriers (transporters) and channels
What define a carrier protein?
Carriers undergo a conformational change during the transport process
What is the mechanism of glucose transport inside the cell?
- Glucose transporter exists in two conformations (T1 and T2)
- Binding of glucose (from blood plasma) may induce a conformation change from T1 to T2
- net transport of solute down its concentration gradient
What is one example of anctive transporters that transport ATP?
One class of membrane proteins that uses ATP hydrolysis to pump ions across membranes are the ubiquitous P-type ATPases
What are some examples of the P type ATPases?
- Na+/K+ ATPase (pumps Na+ out, increase K+ in cell)
- H+/K+ ATPase (pumps H+ out, K+ in; acidifies stomach)
- Ca2+ ATPase (pumps Ca2+ out of cytosol)
What is the mechanism for P type ATPases?
What is the funciton of Na+/K+ ATPase?
Na and K gradient in animal cells is important to maintain cell volume and create transmembrane electrical potential
What are the three different roles of sugars in biology?
- Source of energy/stored fuels
- Provide structure to cells and organism
- Cell biology as part of the cell surface, influencing protein function or specific recognition interactions
What are some examples of carbohydrates providing structure to cells and organisms?
Cellulose in plants
CHitin in arthropods
What is the basic definition of monosaccharides?
Aldehydes or ketones that have two or more hydroxyl groups
Formula [CH2O]n “carbon hydrate”
What is the difference between an aldose and a ketose sugar?
It is aldose because it contains an aldehyde group
What stereoisomer is seen in naturally occuring sugars?
D rather than L
What does the D in D aldose indicate?
D designates the configuration of the asymmetric carbon furthest from the aldehyde group
What are epimers? Give an example
How do hexoses cyclise to form pyranose rings?
The C1 aldehyde reacts with the C5 hydroxyl group to form an intramolecular hemiacetal
Results in 6 membered ring called pyranose
Why is the chair conformation favourable?
Pyranose rings adopt an energetically favourable chair form.
Results in bulky hydroxy groups orientated in less hindered periphery of the sugar
Name these common disaccharides
How many different ways can two D glucose units be linked?
11
What is the structure of glycogen
How can monosaccharides be used as reducing agents?
- Ring opens up and the free aldehyde reduces the copper.
- Itself is oxidised to carboxylic acid.
- Cu2O is a product andc measuring this tells you sugar concentration for blood glucose levels in diagnosing diabetes
What defines the reducing end?
If the anomeric carbon can open up and expose the aldehyde carbon to becoming a reducing sugar
How does the structure of glucose depend on its linkage?
–Glucose residues are linked by (B 1→4) glycosidic bonds
– structure is stabilized by H bonds
– Results in a long flat molecule
How does the properties of cellulose between chains give rise to its structure?
- Chains of cellulose can form interchain hydrogen bonds
- Many chains pack together
- Results in stable supramolecular fibres of great strength
What is the structure of chitin?
- Linear homopolymer of N-acetylglucosamine residues
- Linked B 1,4
- The only difference between it and cellulose is the presence of acetylated amino group at C2
What is the structure of glycogen/starch in terms of the linkage?
- Homopolymer of glucose residues
- Linked alpha 1,4
- Open helix structure rather than linear so that it is an accessible store of sugar
What are the two ways carbohydrates can be linked to proteins?
- Via asparagine residues (N glycans)
- Via serine or threonine residues (O glycans)
What is the structure of an N glycan linkage between protein and carbohydrate?
Sugars are linked to the amide side chain of asparagine
Therefore called N linked oligosaccharides or N glycans
What does the O glycan linkage between proteina and carbohydrate involve>
- Sugars linked to the O atom in the side chain of serine or threonine residues (O linkage)
- Called O linked oligosaccharides or O glycans
How is an oligosacchatide assembled/added to the acceptor?
To what end of the carbohydrate acceptor is the monosaccharide added to?
The monosaccharide is transferred from the nucleotide sugar to the NON reducing end of the carbohydrate acceptor
How is the disaccharide lactose synthesised?
What is the structure of the human ABO antigens
They are glycosphingolipids and A,B differ from O by adding one extra monosaccharide
Which antigen is this?
O antigen
Which antigen is this?
A antigen
Which antigen is this?
B antigen
Genetically what gives rise to the different ABO blood groups?
- There is a single gene encoding the synthesis of ABO blood groups.
- This gene encodes a glycosyltransferase (enzyme) and three forms of it exist.
- An individual inherits one allele from each parent.
How does the glycosyltransferase encode different ABO antigens?
WHat are lectins?
A broad family of proteins which recognise carbohydrates, found in animal plants and microbes
How is the specificity of C type lectins achieved?
- DifferentC-type lectins have different carbohydrate binding specificities
- Changes in residues that interact with the sugar alter the carbohydrate binding specificity of the lectin
What are selectins?
- They are C type Lectins
- Involved in cell to cell adhesion
- Bind white blood cells to sites of injury and allow movement of cells from blood stream to site of infection
How do viruses attach to host cells in terms of binding?
- To infect host cell viruses need to bind to receptors on the cell surface, which may be carbohydrates
How does the influenza virus bind to the host cell?
- Recognises the sialic acid residues present on cell surface glycoproteins
What is the mechanism of anti viral drugs for such as relenza?
- It is an analogue for sialic acid and attacks the sugar binding site of sialic acid binding proteins
- It inhibits the enzyme neuriminidase so that there is no cleavage of sialic acid and the virus remains stuck
- Virus can’t leave the infected cell stopping propagation
What is the structure/conformation of the GLUT transporters?
- 2 states changing from T1 to T2
- 12 transmembrane alpha helices each 20 residues long
What are the common GLUT transporters?
