,Membranes
-prokaryotes have either one cell membrane (gram-positive bacteria) or have inner and outer membranes (gram negative bacteria)
-eukaryotic cells have many membranes
-different membrane in the nucleolus and in mitochondria, chloroplasts in plants, lysosomes, endoplasmic reticulum, golgi and other vesicles involved in intracellul
Membrane functions
1. Provide functional barrier- compartmentalisation of cells
2. Provide cells with energy ( from chemical and charge gradients)
3. Organise and regulate enzyme activity
4. Facilitate signal transduction
5. Supply substrates for biosynthesis and for signalling molecules
6. Protein recruitment platform
Membrane structure
-membranes consist of proteins and lipids
-depending on location of membrane, it contains different ratios of lipids and proteins
-membrane lipid composition changes under homeostatic control
-membranes contain:
aEEEQEEidcahrabinsaka
1.Glycerophospholipids (phospholipids)
2. Sphingolipids
3. Sterols with terminal carboxylic
acid .
Lipid bilayer
-hydrophilic molecules- dissolve in water, contain charged groups or uncharged
groups that can form electrostatic interactions or hydrogen bonds with water molecules
-hydrophobic molecules- insoluble in water- most atoms uncharged and non polar,
cannot form energetically favourable interactions with water
-in water, hydrophobic molecules force adjacent water molecules to reorganise
-if hydrophobic molecules cluster together a smaller number of water molecules is affected- lower free energy cost
-lipids spontaneously aggregate to bury their hydrophobic tails in interior and expose their hydrophilic heads to water
-depending on their shape lipids can form bilayer or micelles
Fatty acids
-fatty acid chains vary in length, double bond number, double bond position and hydroxylation
-the two fatty acid chains in a lipid can be different in length
Nomenclature
-XX:Y n-y -
-XX denotes number of carbons in the chain
-Y indicates the level of chain saturation ( number of double bonds )
-n-y is the position of the first double bonded carbon counting from the methyl terminus
Diversity of membrane lipids
e
Saturated lipid tails: fatty acids in lipid tails that do not have double bonds between adjacent carbon atoms. Lipid tails are relatively straight
Unsaturated lipid tails: fatty acids in lipid tails that contain one or more double bonds between adjacent carbon atoms. Can have a cis double bond (30 degree kink)
-differences in length and saturation of the fatty acid tails influence how phospholipids pack against one another (membrane rigidity)
Glycerophospholipids
-chemical diversity arises from the combination of the two fatty acids, the linkage at the sn-1 position and the head group
-the sn-1 fatty acid is usually saturated (without double bonds) or monounsaturated
-the sn-2 fatty acid is more often monounsaturated or polyunsaturated (multiple double bonds)
n
PS and PE contain reactive
n The anionic phospholipids (PS, PI,
CL) have a net negative charge.
, Sphingolipids
-glycerophospholipids are built on sphingoid base, N-Acyl chain and head group
-most common sphingolipid is sphingomyelin (SM) that has a PC head group
-An acyl chain is attached via an amide linkage.
-The amide group has the ability to form hydrogen bonds- allows interactions of sphingolipids with cholesterol or polar parts of proteins
-N-acyl chains of sphingolipids tend to be more saturated and can be longer than the acyl chains of glycerophospholipids
-Sphingolipids in mammals usually have saturated acyl chains (up to 24 carbons that enable them to pack tightly)
Glycosphingolipids (glycolipids)
-Complex glycosphingolipids have different oligosaccharides as head groups. Their structures are composed of various building blocks (mainly sugars).
-found excusive in the outer leaflet of the membrane.
-Small percentage of the outer leaflet ~5%.
-In plasma membrane, sugar groups are exposed at cell surface.
-Important role in interactions of the cell with its surroundings (cell-cell adhesion).
:
-Allow membranes to act as recognition sites for certain chemicals.
-Ganglioside GM1, Ganglioside GM2, Ganglioside GM3.
-The glycolipids tend to self-associate via hydrogen bonds between their sugars and through their lipids tails
-Self-aggregation of GM1 lipids may be driven by the sugars in GM1 lipids
-Patches of glycosphingolipids can be seen in simulations.
Sterols
-have hydroxyl group and hydrocarbon tail
-cholesterol is most common sterol in animals
-ergosterol found in yeast and fungi membrane
- sitosterol and stigmasterol are found in plants
-the size and shape of cholesterol allows it to interact with pockets in membrane proteins
-its presence increases thickness, packing, compressibility of membranes while it decreases mobility of lipids and proteins
Cholesterol
-Because of its shape cholesterol can align better with saturated side chains e.g. with sphingomyelin.
-Interactions with POPC - its OH group is not buried in the complex.
-Interactions with sphingomyelin - a hydrogen bond is formed between the OH group of cholesterol and the NH group of the sphingolipid.
-The OH group of cholesterol is masked by the polar head of sphingomyelin.
Membrane curvature
-relative size of head group and hydrophobic tails of lipids affect the shape of the lipids and the spontaneous curvature of the membrane
-negative spontaneous curvature of PE leads to bilayer disrupting properties e.g generation of non bilayer membrane intermediates, such as fusion
Lipid diversity
There is two types of diversity
1. Chemical/ structural - specific properties of lipids
2. Compositional diversity between tissues, organelles, and leaflets within the same membrane, affects the collective behaviour of lipids
-Biological membranes contain hundreds of lipids types.
-Bacterial membranes contain PG lipids and cardiolipins – these lipids are only found in mitochondria in eukaryotic membranes.
-In eukaryotic membrane lipid composition varies throughout the cell.
Asymmetry
-erythrocyte membrane has a complex lipid composition
-50% cholesterol
-high concentration of PC and SM lipids in the outer leaflet
-high concentration of PS and PE lipids in the inner leaflet
-lipid asymmetry is functionally important
-phosphatidylserine in animal cells translocates to the extracellular monolayer when such cells undergo cell death, apoptosis
-this acts as signal to neighbouring cells e.g macrophages, to phagocytose the dead cells and digest it
-movement of PS lipids occurs via scramblases
-glycolipids are orientated towards the exterior of the cell
-Second messengers in signalling pathways are oriented towards the interior of the cell e.g. hydrolysis of PI(4,5)P2, results in the formation of secondary me
-prokaryotes have either one cell membrane (gram-positive bacteria) or have inner and outer membranes (gram negative bacteria)
-eukaryotic cells have many membranes
-different membrane in the nucleolus and in mitochondria, chloroplasts in plants, lysosomes, endoplasmic reticulum, golgi and other vesicles involved in intracellul
Membrane functions
1. Provide functional barrier- compartmentalisation of cells
2. Provide cells with energy ( from chemical and charge gradients)
3. Organise and regulate enzyme activity
4. Facilitate signal transduction
5. Supply substrates for biosynthesis and for signalling molecules
6. Protein recruitment platform
Membrane structure
-membranes consist of proteins and lipids
-depending on location of membrane, it contains different ratios of lipids and proteins
-membrane lipid composition changes under homeostatic control
-membranes contain:
aEEEQEEidcahrabinsaka
1.Glycerophospholipids (phospholipids)
2. Sphingolipids
3. Sterols with terminal carboxylic
acid .
Lipid bilayer
-hydrophilic molecules- dissolve in water, contain charged groups or uncharged
groups that can form electrostatic interactions or hydrogen bonds with water molecules
-hydrophobic molecules- insoluble in water- most atoms uncharged and non polar,
cannot form energetically favourable interactions with water
-in water, hydrophobic molecules force adjacent water molecules to reorganise
-if hydrophobic molecules cluster together a smaller number of water molecules is affected- lower free energy cost
-lipids spontaneously aggregate to bury their hydrophobic tails in interior and expose their hydrophilic heads to water
-depending on their shape lipids can form bilayer or micelles
Fatty acids
-fatty acid chains vary in length, double bond number, double bond position and hydroxylation
-the two fatty acid chains in a lipid can be different in length
Nomenclature
-XX:Y n-y -
-XX denotes number of carbons in the chain
-Y indicates the level of chain saturation ( number of double bonds )
-n-y is the position of the first double bonded carbon counting from the methyl terminus
Diversity of membrane lipids
e
Saturated lipid tails: fatty acids in lipid tails that do not have double bonds between adjacent carbon atoms. Lipid tails are relatively straight
Unsaturated lipid tails: fatty acids in lipid tails that contain one or more double bonds between adjacent carbon atoms. Can have a cis double bond (30 degree kink)
-differences in length and saturation of the fatty acid tails influence how phospholipids pack against one another (membrane rigidity)
Glycerophospholipids
-chemical diversity arises from the combination of the two fatty acids, the linkage at the sn-1 position and the head group
-the sn-1 fatty acid is usually saturated (without double bonds) or monounsaturated
-the sn-2 fatty acid is more often monounsaturated or polyunsaturated (multiple double bonds)
n
PS and PE contain reactive
n The anionic phospholipids (PS, PI,
CL) have a net negative charge.
, Sphingolipids
-glycerophospholipids are built on sphingoid base, N-Acyl chain and head group
-most common sphingolipid is sphingomyelin (SM) that has a PC head group
-An acyl chain is attached via an amide linkage.
-The amide group has the ability to form hydrogen bonds- allows interactions of sphingolipids with cholesterol or polar parts of proteins
-N-acyl chains of sphingolipids tend to be more saturated and can be longer than the acyl chains of glycerophospholipids
-Sphingolipids in mammals usually have saturated acyl chains (up to 24 carbons that enable them to pack tightly)
Glycosphingolipids (glycolipids)
-Complex glycosphingolipids have different oligosaccharides as head groups. Their structures are composed of various building blocks (mainly sugars).
-found excusive in the outer leaflet of the membrane.
-Small percentage of the outer leaflet ~5%.
-In plasma membrane, sugar groups are exposed at cell surface.
-Important role in interactions of the cell with its surroundings (cell-cell adhesion).
:
-Allow membranes to act as recognition sites for certain chemicals.
-Ganglioside GM1, Ganglioside GM2, Ganglioside GM3.
-The glycolipids tend to self-associate via hydrogen bonds between their sugars and through their lipids tails
-Self-aggregation of GM1 lipids may be driven by the sugars in GM1 lipids
-Patches of glycosphingolipids can be seen in simulations.
Sterols
-have hydroxyl group and hydrocarbon tail
-cholesterol is most common sterol in animals
-ergosterol found in yeast and fungi membrane
- sitosterol and stigmasterol are found in plants
-the size and shape of cholesterol allows it to interact with pockets in membrane proteins
-its presence increases thickness, packing, compressibility of membranes while it decreases mobility of lipids and proteins
Cholesterol
-Because of its shape cholesterol can align better with saturated side chains e.g. with sphingomyelin.
-Interactions with POPC - its OH group is not buried in the complex.
-Interactions with sphingomyelin - a hydrogen bond is formed between the OH group of cholesterol and the NH group of the sphingolipid.
-The OH group of cholesterol is masked by the polar head of sphingomyelin.
Membrane curvature
-relative size of head group and hydrophobic tails of lipids affect the shape of the lipids and the spontaneous curvature of the membrane
-negative spontaneous curvature of PE leads to bilayer disrupting properties e.g generation of non bilayer membrane intermediates, such as fusion
Lipid diversity
There is two types of diversity
1. Chemical/ structural - specific properties of lipids
2. Compositional diversity between tissues, organelles, and leaflets within the same membrane, affects the collective behaviour of lipids
-Biological membranes contain hundreds of lipids types.
-Bacterial membranes contain PG lipids and cardiolipins – these lipids are only found in mitochondria in eukaryotic membranes.
-In eukaryotic membrane lipid composition varies throughout the cell.
Asymmetry
-erythrocyte membrane has a complex lipid composition
-50% cholesterol
-high concentration of PC and SM lipids in the outer leaflet
-high concentration of PS and PE lipids in the inner leaflet
-lipid asymmetry is functionally important
-phosphatidylserine in animal cells translocates to the extracellular monolayer when such cells undergo cell death, apoptosis
-this acts as signal to neighbouring cells e.g macrophages, to phagocytose the dead cells and digest it
-movement of PS lipids occurs via scramblases
-glycolipids are orientated towards the exterior of the cell
-Second messengers in signalling pathways are oriented towards the interior of the cell e.g. hydrolysis of PI(4,5)P2, results in the formation of secondary me
