membranes and lipids Flashcards
describe the 2D fluid mosaic of membrane structure
lipids form bilayer in 2D sea which proteins float in and can move around
describe the formation of the lipids in the bilayer
headgroups of the lipids are hydrophilic and (polar) are on the outside
lipid tails are hydrophobic (non polar) and stay in the middle of the layer
what is the most abundant phospholipid in cells and what are they derived from
glycerophospholipids derived from glycerol-3-phosphate
give examples of different types of lipids
PIP glycerophospholipids sphingolipids glycosphingolipids sterols cholesterol
what are fatty acid chains and why are they unique
they are made by acetate and added via CoE A
what are sphingolipids made from
sphenoid base, N acyl chain and head group
what characteristic of sphinoglipids allows them to interact with polar molecules or cholesterol
can form hydrogen bonds
explain the structure and role of glycopsphingolipids (glycolipds)
composed mainly of sugars
make around 5% of outer leaflet of the membrane
they play an important role in cell to cell adhesion and can act as recognition sites
what are gangliocydes
they are abundant in the brain, they are a sphingosine plus sugar groups which can present receptors - they attach to lipid rafts and only found on the outer surface of the membrane
where is cholesterol found in animal membranes
between the lipid molecules
what is a lipid raft
they are subdomains of the plasma membrane which contains high concentrations of cholesterol and glycosphingolipids
what are the functional significances of lipid rafts
can attach receptors
can drift
what are caveolae
a type of lipid raft which invaginate the cell membrane which can contain many proteins and can be used for taking up nutrients
what is lipid bilayer asymmetry
the fact that the monolayers that make up the bilayer an have different structures within them
why does lipid interdigitation occur
due to lipid length asymmetry which reduces the lipid bilayer thickness
what are translocaze enzymes
flip phospholipids across the membrane
what do scrambles enzymes do
randomise the normal distribution and oppose translocaze enzymes
what does phosphatidylserine do in apoptosis and blood clotting
acts as a pro coagulation surface. it is externalised by collagen and thrombin mediated activity
externalisation of phos.. can also lead to recognition of cell and therefore apoptosis
what causes membrane curvature
the relative size of the head group and the tail affect the shape fo the bilayer and the curvature
why is spontaneous negative curvature a bad thing
can lead to bilayer disrupting properties which can lead to fusion and non-bilayer intermediates
what is the role of desaturates
introduce double bonds into fatty acids
what are the three types of membrane proteins
integral (intrinsic) membrane protein (span inside and out)
lipid linked membrane protein
peripheral (extrinsic membrane protein (only found on one side)
what is the structure of integral membrane proteins
what is the problem with extracting them
can be single or multiple transmembrane segments - these regions are mainly made up of amino acids and hydrophobic side chains
extracting them will disrupt the membrane using organic solvents or detergents
what are PIP lipids
head group phosphorylation at position 3 4 and 5
PIP(4,5)2 is most abundant
found in the inner leaflet of the membrane
they usually face inside of the cell and are signalling molecules for cascade pathways
give an example of an integral membrane protein - simple and multiple
glycophorin A - single domain
extra cellular domain is glycosylated
bacteriorhodopsin - multiple domain - 7 transmembrane domains
how are proteins bound to lipids in the membrane
covalently linked to lipid which is inserted into the membrane
give some examples of lipid bound proteins
prion protein
trial proetins
signalling proteins
insulin receptor
where do peripheral proteins interact (they can be readily removed by high salt concentration and soluble in aqueous solution)
only with the hydrophilic heads and with other proteins via ionic interactions
what are some examples of peripheral membrane proteins
cytoskeletal proteins such as: spectrin - form long filaments actin - joins spectrin filaments ankyrn - bridges spectrin and band 3 band 4.1 - stabilises spectrin-actin interaction
what is the role of peripheral membrane proteins in RBC’s
maintains shape and rigidity and restricts lateral motion of integral membrane proteins
what is hereditary spherocytosis / elliptocytosis
mutations in genes encoding spectrin and ankyrin result in abnormal shape which become degraded by the spleen and results in anaemia
what is the role of amyloid b peptide in alzheimers
amyloid beta peptide forms plaques in the brain causing neuronal atrophy which causes loss of part of brain dealing with memory
where are carbohydrates found in the cell membrane
either watched to proteins or attached to the bilayer ie glycoprotein or glycolipid - they are found near exclusively on the extracellular face of the cell
what is the difference between O linked and N linked glycoproteins
O linked - carb attached to serine or threonine - often shorter
N linked sugars - often large and unbranched - connected to asparagine
why are carbs important to the cell
stabilises proteins and used in intracellular recognition eg blood group antigens on RBC
what is amyloid precursor protein and what is it cleaved by - what does it lead to
integral membrane protein with transmembrane spanning domain which is cleaved by beta secretase, then by sAPPB and Y secretase - leads to AB42 leads to formation of senile plaques
where do senile plaques tend to from in alzheimers
cholesterol rich lipid rafts which produces amyloid beta protein
what is the relevance of ApoE4 in Alzheimers
it is involved in cholesterol transport and is more prevalent in alzheimer’s patients
what do statins do
lower amyloid beta production in cells and cholesterol content
what is prenylation and where does it occur
it is the addition of hydrophobic molecules to a protein or compound. it occurs at cysteine residues at C terminus and allows proteins to be inserted into the membrane
what is palmitolyation
covalent attachment of fatty acids to a cysteine residue
which molecules can pass through a pure lipid bilayer the easiest
gases
what is a pure bilayer permeable to
water, gases, small polar molecules and hydrophobic molecules (benzene)
what is the rate of diffusion proportional to and what is the movement direction
the concentration gradient
from areas of high to low concentration
what is facilitated diffusion
occurs down the gradient - no energy required and is dependant on integral membrane proteins
similar kinetics to enzymes
what are ionophores types
give examples
(facilitated diff)
they can be carrier or channel forming
carrier - carry across the membrane to shield from hydrophobic area eg antibiotic vanomycin (specific to K+)
channel forming - channel that allows free flow of ions eg antibiotic grimicidin specific to Na+ and K=
what are ion channels and what are they used for
facilitated diff
allow rapid and gated movement of Na+ and K=
ions flow down gradient
nerves, signal transduction
how does glucose cross the barrier
attaches to GLUT-1 which undergoes conformational change and allows diffusion of glucose into the cell - dependant on glucose conc
what happens to glucose uptake in RBC
converted to G6P by hexokinase
what are aquaporins
water channel proteins - responsible for water flow - its is a tetrameter with 4 pores fro H20 to pass
28KDa with 6 trasndomain a helices
what are the two types of active transport
ATP driven
Ion driven
what are some examples of ATP driven transport
Na+/K+ ATPase
which maintains high k+ inside the cells and low Na+ inside the cell
3 Na out and 2 K in - works against concentration gradient
what is ion driven active transport, give examples
movement of a molecule coupled with an ion
symport - both in one direction eg Na+ glucose transporter
antiport (opposite direction) eg Na+ Ca2+
what are the two different types of exocytosis
constitutive - occurs in all cells constantly for secreted proteins and plasma membrane proteins
regulated - occurs via specific signal eg release of insulin or neurotransmitters
explain exocytosis at the nerve terminal
calcium dependant - impulse means ca into cell causes synaptic vesicles to fuse with membranes and release neurotransmitter
give three examples of endocytosis
phagocytosis
pinocytosis
receptor mediated endocytosis
describe process of phagocytosis by dendritic cells, neutrophils and macrophages
pathogen engulfed by pseudopodia and ingested into vacuole which fuses with lysosome then foreign antigens displayed on membrane
describe receptor mediated endocytosis
Receptor-mediated endocytosis is the selective uptake of macromolecules from the extracellular fluid via clathrin-coated pits and vesicles. The ligand being taken up must first bind to a specific cell surface receptor. The receptor-molecule complexes accumulate in a clathrin coated pit and then endocytosed in a clathrin-coated vesicle
describe gluoce transport in the intestinal epithelium
- Na+/glucose transporter only in apical membrane, glucose transporter only in basolateral
- Movement of glucose from gut into epithelial cell driven by movement of Na+ ions down conc. gradient through Na+/glucose symporter
- Glucose diffuses across basolateral membrane into blood stream
- Conc. of Na+ ions maintained at low level in cell by Na+/K+ ATPase in basolateral membrane
- As glucose moves through epithelial cell, water follows by osmosis
what is an oral rehydration therapy
contains water salts such as Na K and glucose
needed as with cholera can’t just have water as uptake of glucose is dependant on Na+ which then allows water to flow back into cells
what are the three stages of remote cell signalling
1) reception of extracellular signal by cell
2) transduction of signal from outside to inside the cell
3) response, activation of cellular response
what is contact signalling and give an example
juxtacrine - where cell displays plasma membrane bound molecules
eg T helper cell activated by antigen presenting cell which causes activation if the correct binding shape
what are the 3 types of cell signalling
paracrine - remote cell signalling
contact signalling (juxtacrine)
contact signalling via gap junctions
describe the process of cell communication via gap junctions and give an example
cytoplasms are directly joined by connexion proteins to adjacent cells eg cardiac myocyte cells
what are the four main types cells communicate around the body
autocrine - acts on itself
paracrine - signal acts on nearby cells
endocrine - released into blood and distant target
neuronal - nerve impulses - uses neurotransmitters
what is the difference between lipid hormones and hydrophilic hormones give examples
hydrophilic bind to the cell surface but lipid hormones act on the inside
hydrophilic - catecholamines and peptide hormones
lipid base - steroids
thyroid hormones
sterol hormones
what are the 4 receptor classes and what are the sub class differences
ligand gated ion channel g protein coupled receptors kinase linked receptors nuclear hormone receptors nuclear hormone receptors are the only ones that act intracellularly
describe how ligand-gated binding channels work
works very fast, binding of ligand causes conformational change to allow specific ions to flow through and alter the cells electrochemical gradient. electrons flow down gradient.
these channels typically open in response to change in membrane potential
describe how GPCR’s work
they are integral membrane proteins which are coupled with intracellular effector system. transmembrane regions. when a hormone binds to a specific GPCR receptor - conformational change facilitating inside cell with G protein which inhibits or activates down stream proteins or DNA
describe how kinase linked receptors work
they have a single transmembrane helix with a large extracellular binding domain and an intracellular catalytic domain. the receptor itself is an enzyme which directly effects gene expression by affecting phosphorylation of different tyrosine
describe how nuclear hormone receptors work
they are present in the cytosol or nucleus - hormones diffuse across the cell membrane and interact with receptors which then causes translocation into the nucleus to form a hormone receptor complex which binds to regions of DNA affecting transcription
what does the RAS affect
Controls BP, blood volume and electrolyte homeostasis
describe the mechanism of the RAS
it is stimulated by decrease in blood volume, blood pressure or Na+
Renin from the kidney cleaves angiotensin 1 from angiotensinogen which is made in the liver. ACE then cleaves to angiotensin 2
this causes vasoconstriction of arterioles, retains water and salts in he blood so blood volume increases and is controlled by negative feedback
where is ACE found
membrane bound in the pulmonary and renal epithelium
give some examples of monoamines
noraA adren dopamine histamine serotonin
give some examples of amino acids
glutamate
aspartate
glycine
GABA
give some examples of peptides
endorphins, substance P, neurokinins
neurotensin
what does AG2 target and what are the effects
receptors are al GPCRs AT1 - vasoconstriction increased NA release Na reabsorption aldosterone growth AT2 - antihypertrophic antihyperssensitive opposes AT1 effects
give an example of a lipid neurotransmitter
anandamide
describe the life cycle of a neurotransmitter
synthesis in nerve terminal
storage in synaptic vesicles
release into synaptic cleft by exocytosis in response to action potential
receptor activation on post synaptic membrane
neurotransmitter deactivation via enzyme metabolism or reuptake
what is depression believed to be caused by
functional deficit of monaminergic transmission eg NA, dopamine, serotonin
what are the 5 ways depression is treated
monoamine reuptake inhibitors such as TCA’s, SSRI’s, SNRI’s
monamine oxidase inhibitors (stop the breakdown of monoamines in the presynaptic knob so more is available)
atypical antidepressants
electroconclusive therapy
mood stabilising drugs such as lithium
give three examples of gastrotrasnmitters and what they are
they are gaseous molecules synthesised in the body which act as signalling molecules such as NO, CO and H2S
what is the problem with gastrotransmitters
they are environmental pollutants which can readily cross the cell membrane and induce paracrine signalling
what are the effects of CO and high vs low conc
high conc leads to neurological and cardiovascular disorder
in low conc can stimulate vasodilation and be cardio/neuro protective
what effect does NO have
causes relaxation of smooth muscle and therefore vasodilation
what is signal transduction
converts extracellular 1st signal from messenger into a change in cellular function
what are the three main stages of signal transduction
reception
transduction (hierarchy, amplification, specificity, complexity)
response
describe with an example what hierarchy is in signal transduction
components of a pathway arranged in a particular way to transmit a signal from the outside to change something on the inside of the cell
what is amplification
from a single molecule of the primary messenger which could induce many downstream molecules leading to many changes inside the cell from secondary messengers affecting kinases which affect protein activity
how are signal transduction pathway specific and give an example
one messenger molecule may bind to the same receptor but on different cells and elicit a very different response between them
adrenaline can binds to different tissues and caused a different response depending on the cell type
why is signal transduction complex
many different types of receptors, G proteins, enzymes, 2nd messengers - lots of cross talk and cell type specificity
what do GTPases do?
hydrolyse GTP to GDP
how are G proteins secured to the cell
anchored to internal surface of cell membrane via lipid tails ie prenylation
what are the two major groups of G proteins and give examples
g protein - receptor associated - heterotrimeric such as A, B, Y subunits (Gas, Gai, Gaq)
small GTPases - monomeric such as RAS and RHO
how are G proteins activated and stopped
switch on by ligand binding then switched off by GTPase activity - inactive when GDP (no Pi) bound but active when GTP bound
describe how the Gs pathway works
stimulatory pathway - alpha subunit of Gs bound to GDP and in inactive state. binding of ligand to receptor causes G protein to release GDP and attach GTP. the a unit bound to GTP dissociates from the g protein and binds to adenylate cyclase which converts ATP into cAMP (secondary messenger). GTPases convert GTP back to GDP releasing inorganic phosphate and a unit rebinds with b and Y
what affect does Gs have vs Gi on cAMP
Gs increases
Gi decreases
after inactivation of Gs what breaks down cAMP
phosphodiesterase breaks it down into water and H2O
what is the role and mechanism of the Gq pathway
Gq stimulates phospholipase which increases DAG and IP3. Phospholipase C turns PIP two into DAG and IP3
what is the role of DAG
it stays in the membrane where it activates protein kinase C (which can also be activated by Ca)
what is the role of IP3
released into the cytosol where it triggers Ca release
which g proteins do cholera and pertussis toxin affect
cholera = Gs pertussis = Gi
what are the symptoms and mechanism behind cholera toxin and treatment
bacterial infection through dirty water or food causes diarrhoea and vomiting (severe dehydration) - treated with ORT
toxin stimulates Gs pathway and inhibits GTPases so remains in an active state - in intestinal epithelial cells high cAMP results in excess loss of Cl- so water moves with it from cells into the lumen
what are the symptoms behind whooping cough (pertussis toxin) and the mechanism of action
airborne through droplets which can be treated by antibiotics and prevented with vaccination this pathway inhibits Gi therefore an overall stimulatory effect on cAMP leading to increased insulin secretion and sensitivity to histamine
what are some examples of PDEs inhibitors
caffeine and viagra (stop breakdown of cAMP)
name 5 secondary messengers
cAMP cGMP DAG IP3 Ca
where does Ca come from to take effect on a cell
can come from extracellular routes or from stores within the ER - also founding the mitochondria
how is cGMP produced
from GTP via enzyme guanylyl cyclase or by NO
what are the three main groups of protein kinases
serine/threonine kinases
tyrosine kinases
dual specificity kinases
where is phosphate added to on an amino acid
to the OH group
what are protein kinase inhibitors used for
therapeutic agents fro cancer, HIV, RA, cardiovascular disease
what is gleevec (imatinib)
used to treat myelogenous kinases inhibits receptors kinase tyrosine
what are the functions of lipids
energy store component of cell membrane soluble fat soluble vitamins biosynthetic precursors signalling molecules
where does cholesterol come from and why does it need a carrier
25% from diet and the rest made from the liver (also intestine but small)
it is insoluble so is attached to a lipoprotein
what are the four types of lipoprotein classification
chylomicrons (largest)
VLDL
LDL
HDL (smallest)
what is the role of VLDL
transport lipids made in the liver to peripheral tissues
what is the role of LDL’s and why can they be bad
provide cholesterol for peripheral tissues - it is the main cholesterol carrier.
can be damaging - has single layer of ApoB on outside - can be oxidised leading to pro inflammatory response and protherogenic leadings to CVD
what is the role of HDL and why are they good
tranport cholesterol to liver from peripheral tissues - contains mainly apoA which is protected against oxidation and has anti-inflammatory properties
what is the general structure of a lipoprotein
The external monolayer contains phospholipids, cholesterol and apolipoproteins. Cholesterol esters and triacylglycerols are located in the particle core.
what are the four classes of apolipoproetins
ApoA - present in HDL mediates taking away of cholesterol from peripheral cells and influx to the liver
ApoB - recognises ApoB/E receptors - facilitates LDL uptake
ApoC - activator of lipoprotein lipase - transferred between lipoproteins
ApoE - stabilises VLDL for cellular uptake
what does lipoprotein lipase do
hydrolyses triglycerides to fatty acids that can be taken up by target tissues and used fro energy production
describe the life cycle of VLDL
made by liver - transport lipids to tissues broken down by LPL and become LDL which causes release of cholesterol
why is HDL good
takes up cholesterol from the blood and transports back to the liver
how does the liver remove cholesterol
in the form of bile slats
what does a scavenger receptor do
recognises mature HDL and takes in liver to secrete bile
what is the role of cholesterol in atherosclerosis
major constituent of atheromatous plaques in cholesterol enriched LDL as excess is deposited in arteries
describe the development of atherosclerosis over many decades
fatty streak
fibrous plaque
advanced plaque
myocardial infarction
how do statins work as a treatment for lowering cholesterol
cholesterol is made by HMG-CoA reductase (from mevalonate) - statins inhibit this enzyme
this increases expression of LDL receptor which means more cholesterol is taken up from the blood
how do statins have a pleiotropic effect
they have mulitbenefical effect - improve endothelial function
antioxidant properties , inhibition of inflammation and stabilise atherosclerotic plaques to reduce risk of rupture
