membranes Flashcards
what are 3 types of lipids found in membranes
- glycerophospholipids (phospholipids)
- sphingolipids (phospholipids that have an amide bond between a fatty acid and a sphingosine)
- sterols - subgroup of steroids, have a hydroxyl group and hydrocarbon tail
how does membrane curvature occur
occurs due to the relative size of the head group and hydrophobic tails of the membrane.
cyclindrical phospholipids lead to straight membrane
conical phospholipids lead to negative curvature
inverted-conical leads to positive curvature
what are membrane domains/rafts
sections of membrane enriched in cholesterol and sphingomyelin. rafts are thicker than normal membrane due to their lipid composition
what are the 2 forms of carbohydrate found in membranes?
glycolipids and glycoproteins
what is a O-linked glycoprotein?
carbohydrate attached to a serine or threonine amino acid
in proteins the sugars can be attached to the hydroxyl group in the side chain of serine or threonine = O-linked
consist of 3-5 sugars
what are N-linked glycoproteins?
carbohydrate chain attached to an asparagine amino acid only when asparagine is in consensus sequence Asn-X-Ser/Thr, they are large, branched structures with as many as 30-40 sugar residues
what is the functional use of membrane carbohydrates?
located of the extracellular surface of the membrane
- stabilises porteins
- intracellular recognition- blood group antigens (ABO) are on lipids
the role of amyloid beta peptide in alzheimers disease
alzheimers disease is associated with amyloid plaques composed of the protein amyloid beta (AB)
what is the role of cholesterol in alzheimers?
causes increased incidence of amyloid plaques in those dying of heart disease
apolipoprotein E4 involved in cholesterol transport is more prevalent in alzheimers
statins prevent alzheimer but cannot slow its progression
how are rafts involved in alzheimer disease
certain protein clusters in rafts that have important roles in biological processes - e.g alzheimers
the proteolytic processing of APP in rafts produces amyloid beta peptide whereas in other regions, cleavage of APP prevetns formation of amyloid-beta
name 3 different types of membrane protein
integral/intrinsic membrane proteins
lipid-linked membrane proteins
peripheral/extrinsic membrane protiens
what are intrinsic/integral membrane proteins?
membrane proteins that stick all the way through the membrane
they span the membrane with single or multiple transmembrane segments
interact with fatty acid chains in hydrophobic interior bilayer
TM regions made up predominantly of amino acids and hydrophobic side chains
can only be extracted from the membrane by distrupting the membrane with organic solvents or detergents
they come in all shapes and sizes
what are lipid-linked membrane proteins?
lipids stuck in the membrane
proteins are covalently linked to the lipid
this lipid is inserted in the membrane
different proteins use different lipids for attachment
what are peripheral/extrinsic membrane proteins
attached less tightly, on the surface
do not directly kinteract with the hydrophobic core of the bilayer
interact with the lipid headgroups or with other membrane proteins through ionic interactions
interact with lipid headgroups of other proteins
readily removed by high salt concentration
can be cytoskeleton proteins such as spectrin and actin
what are the different types of passive diffusion?
simple diffusion and facilitated diffusion
what is simple diffusion?
transport of gases, hydrophobic molecules and small molecules.
no metabolic energy is required
small molecules only
no specificity
rate of diffusion is proportional to concentration gradient
what is facilitated diffusion? and 4 examples
occurs down conc. gradient
no energy required
proteins are specific
depends on integral membrane proteins (carriers, permeases, channels and transporters)
ionophore - ion carrier of bacteria, used as antibiotic to discharge ion gradient of target cell = kill cell by allowing free movement of K+
ion channels - allow rapid and gated passage of anions and cations (normally closed and opened witha stimulus). highly selective
glucose transport = trasnport of glucose into erythrocytes, facilitated diffusion and integral membrane protein - glucose transporter (GLUT1)
Aquaporins = water channel proteins, abundant in erythrocytes and kidney cells
what are the two types of active trasnport?
ATP-driven and Ion-driven
how does ATP-driven active transport work?
energy from the hydrolysis of ATP e.g. Na+/K+ ATPase
how does ion-driven active trasnport work?
energy is from the movement of an ion down its concentration gradient - either symport (in which both the ion and ther molecule are trasnported across membrane in the same direction) e.g. Na+/glucose transporter or antiport (travel in opposite directions) e.g. Na+/Ca2+ exchanger
what are the two types of membrane trasnport for macromolecules?
exocytosis and endocytosis
what is exocytosis?
constitutive (continuous/regulated) :
all cell, secrete proteins and plasma membrane proteins
regulative (occurs in response of specific signal)
-specialised cells and is Ca2+ dependent
what is endocytosis?
phagocytosis = ingesting of large particles by specialised cells
pinocytosis = cell drinking - taking up of fluid (all cells)
receptor mediated endocytosis
= selective (receptor recognition), involves clathrin-coated pits and vesicles, good for concentrating low levels of macrophages.
e.g. cholesterol uptake - LDL receptor can be exploited by viruses to gain entry to cells
describe oral rehydration therapy
uptake of glucose is dependent on Na+, therefore patients are given an oral solution of glucose and Na+.
this increases the osmotic pressure in epithelial cells so water follows
what are the 3 main stages of intracellular signalling
converts primary messenger into a change in cellular function
- reception
- singal transductase
- cellular response
what are the 4 super families of receptors
ligand-gated ion channels
G-protein coupled receptors
kinase linked receptors
nuclear hormone receptor
what are ligand gated ion channels
ionic receptors, binding and channel
opening is very fast
involved in synaptic trasnmission
binding cuases conformational chnage in the channel protein such that specific ions can flow through to change cells pd
ligand binding sites are on the extracellular side
e.g nicotine acetylcholine receptor nAChR which increases Na+ and K+ permeability as Na+ moves in and K+ moves out of cell = membrane depolarisation
what are G-protein coupled receptors
-metabotropic or heptahelical receptors
couple to an intracellualr effect system via a G-protein
integral membrane protein receptors consisting of a single polypeptide with 7 membrane spanning alpha helical regions connected by alternative extracellular and intracellular loops
bidning of hormones (ligands) to GPCRs is the result of interactions with extracellular loop regions and/or transmembrane domians
targets include peptide hormones and neurotransmitters
e.g. muscarinic Ach receptor, adrenoreceptors, angiotensin ii receptors
what are kinase-linked receptors?
single transmembrane helix - large extracellular binding domains and intracellular catalytic domain
catalytic receptor - receptor is itself an enzyme
non-catalytic receptors - act through cytoplasmic tyrosine kinases e.g. insulin
what are nuclear hormone receptors
intracellular receptors in the cytosol or nucleus - ligand activated transcription factors.
regulate gene transcription
e.g. steroid and thyroid hormones
hormones diffuse across the plasma membrane
interact with cytosolic of nuclear receptors
form hormone receptor complexes
bind to regions of the DNA and affect gene transcription
what are the major neurotrasnmitters?
acetylcholine
monoamines - noradrenaline, adrenaline, dopamine, histamine, seratonin
amino acids -Glutamate, aspartate, glycine, GABA
peptides - endorphins, substance P, neurokinins, neurotensin
lipids - andandamide (natural cannabis)
describe the lifecycle of a neurotransmitter
- synthesis (in the nerve terminal)
- storage (in synaptic vesicles within nerve terminals)
- release (into synaptic cleft from the pres-synaptic vescicles via exocytosis - Ca2+ dependent)
- receptor activation (diffusion across the synaptic cleft and act on specific receptors located on the post synaptic cell)
- neurotransmitter inactivation (action is short-lived due to enzyme metabolism and/or reuptake into pre-synaptic nerve terminal
how can neurotransmitters be targetted for treatment of depression
depression is a functional deficit of monoaminergic trasnmission - noradrenaline, dopamine and seratonin.
monoamine reuptake inhibitors -TCAs (tricyclic antidepressents), SSRIs (selective seratonin reputake inhbitors) and SNRIs (seratonin/noradrenaline reuptake inhibitors) monoamine oxidase inhbitors (MAOIs) miscellaneous atypical antidepressants electroconvulsive therapy (ECT) mood stabilising drugs e.g. lithium
what are the 4 general features of signal transduction pathways
Hierarchy
aplification
specificity
complexity
what are G-proteins?
guanine nucleotide binding proteins. GTP is a high energy molecule that activates G-proteins. G-proteins are GTPases, they hydrolyse GTP to GDP, they are lipid anchored membrane proteins
what are the 2 main groups of G-proteins?
heterotrimeric - receptor associated G-proteins
monomeric GTPases
name 3 types of receptor associated G-proteins
Gs (stimulatory), Gi (inhibitory) and Gq
what does Gi do?
Gi inhibits adenylate cyclase and reduces cAMP levels
what does Gs do?
activates adenylate cyclase so increases cAMP levels
what does Gq do?
effector enzyme = phospholipase C and second messenger is DAG
casues IP3 to increase
what are the effects of the cholera toxin on different G-proteins?
cholera toxin inhibits GTPase activity of Gs therefore GTP remains bound to Gs and stays ‘ON’.
=over stimulation of adenylate cyclase and accumulation of cAMP.
in intestinal epithelial cells, elevated cAMP increases loss of Cl- ions causing water to follow down resultant osmotic gradient into intestinal lumen = dehydration
what is the role of adenylate cyclase?
converts ATP into cAMP and PPi by catalysing the removal of a phosphate group
what is the role of guanylate cyclase?
converts GTP into cGMP and PPi
What is the role of phospholipase C?
catalyses the production of DAG and IP3 from the membrane lipid PIP2.
IP3 causws calcium channels to open and DAG stimulates protein kinase C
name 5 secondary messengers
cAMP, cGMP, IP3, DAG and Ca
what are protein kinases?
enzymes that facilitate the transfer of a phosphate group from ATP to a specific amino acid residue (Ser, Thr, Tyr) on a specific protein
what are the 3 main types of protein kinases?
serine/threonine kinases (phophorylate Ser and/or Thr residues - e.g. PKA, PKC, PKG)
Tyrosine kinases (phosphorylate only Tyr residues, receptor TKs e.g. insulin receptor and non receptor TKs e.g. Src) both receptor and non receptor
dual specificity kinases - phosphorylate Ser/Thr and Tyr residues e.g. MAP kinase kinases (MKKs)
what are phosphatases?
they remove amino acid residues to oppose the effects of kinases and switch the switch in the opposite direaction
what are the 2 main groups of phosphatases?
Ser/Thr directed phosphoprotein phosphatases (PPPs)
Tyr - directed phosphotyrosine phosphatases (PTPs)
what are protein kinase cascades?
signalling pathways that phosphorylate toinduce change in a proteins conformation/function
phosphorylate transcription factor that alters gene transcription and hence protein expression levels.
what is the generalised structure of lipoproteins
the external monolayer contains phospholipids, cholesterol and apolipoproteins. cholesterol esters and triacylglycerides are located in the particle core
each lipoprotein has a distinguishing function mediated by specific protein strands embedded in the surface of lipoproteins - apolipoproteins
what do chylomircons dO?
transport dietary fats from intestine to tissues
what do VLDL do?
transport lipids made in the liver to peripheral tissues
what do LDL do?
provide cholesterol for peripheral tissues . the main cholesterol carrier
what does HDL do?
transport cholesterol to liver from peripheral tissues
what is the role of cholesterol in atherosclerosis
a main constituent if atherosclerotic plaques is cholesterol enriched LDL
how do statins work?
statins inhibit HMG-GaA reductases, this reduces mevalonate and hence synthesis of cholesterol. this causes increased expression of LDL receptor. this leads to increased uptake of cholesterol from the blood
what is pleiotropism?
when a drug has unexpected uses other than the one used for
how are statins pleiotropic?
the benefits of statins cannot be fully explained by cholesterol lowering as other cholesterol lowering drugs do not give the same protections statins improve endothelial dysfunction antioxidant properties inhibition of imflammatory responses stabilisee atherosclerotic plaques
what are the 3 main types of membrane lipids
glycerophospholipids
sphingolipids
cholesterol
which type of lipid makes up 50-90% of membrane lipids
cholesterol
why do phospholipids form a bimolecular layer in water?
becuase the hydrophobic lipids chains are repelled by the water but the polar head can interact with water molecules
give a change in membrane lipid composition that would increase fluidity of the membrane
decreasing length of fatty acid chain
increasing number of saturated bonds in fatty acids
reducing cholesterol
what is the membrane fluid mosaic model
the membrane is a 2D solution of orientated proteins and lipids
in alzheimers disease, what do senile plaques consist of?
amyloid beta peptide
what is the difference between how peripheral and integral membrane proteins can be extracted from the membrane in the labatory
peripheral proteins can be extracted witha solution of high salt but integral proteins can only be exracted by distrupting the membrane with detergent because they are associated with the hydrophobic core of the bilayer
why would a protein be prenylated?
to anchor the protein to the membrane
in glycoproteins O-linked sugars are attached to which 2 amino acid residues?
serine or threonine
why is facilitated diffusion kinetics saturable
Because it requires transport proteins, which will be saturated at high levels of the molecule being transported.
why is D-glucose taken up more readily than L-glucose by erythrocytes?
the transporter protein has a much higher affinity for D-glucose
why is the Na+/K+ pump not an example of facilitated diffusion
energy is required from ATP to pump Na+ and K+ against their concentration gradients
why does oral rehydration therapy include glucose and NaCl
glucose transport into intestinal cells is coupled to trasnport of Na+
as these two are taken up by cells, the osmotic pressure increases and water flows in by osmosis
what is autocrine signalling?
when the cell responds to a signal released by the same cell
what is homeostasis?
bodys ability to physiologically regulate its internal environment
in relation to hormones what is negative feedbakc
the hormone released by the target gland acts on the tissue that releases the hormone to switch off release of the hormone
what is a ligand gated ion channel?
an ion channel that opens when it is bound to the ligand
how many membrane spanning regions are present in G-protein coupled receptors
7
what is the common property of hormnes that bind to nuclear receptors
they are lipophillic, as they must cross the lipid membranes to reach the nucleus
in RAS which protein is cleaved by renin
angiotensinogen
which molecule binds to the AT1 receptor?
angiotensin ii
what is the effect on blood pressure of vasoconstriction
BP increases
why is ACE inhibitor drug such as captopril used to treat heart disease caused by high blood pressure
inhibiton of the engiotensin coverting enzyme reduces the amount of angiotensin ii that can bind to AT1 receptor, thus lowering blood pressure
why are some monoamine uptake inhibitors used to treat depression
it is thought that depresion involves reduced function of monoamine nerve signalling in the CNS
monoamines are released by one nerve to stimulate the next nerve. they are then taken back up by the nerve that released them. inhibition of this uptake process will increase the length of time that the signalling molecule is available to stimulate the nerve on which it acts on
what conversion is catalysed by G-proteins
GTP –> GDP
they have GTPase activity
what is the molecular mechanism of action of cholera toxin
inhibits GTPase activiy of the Gs subunit
which enzymes break down cyclic nucleotides
phophodiesterases
which effect enzyme produces DAG and IP3 as second messengers>
phospholipase C
Which amino acids can be phosphorylated by protein kinases
serine
threonine
tyrosine
NFkB is a transcription factor, what happens when it binds to a gene promoter
transcription of the gene increases
what is vacuole based exocytosis called and where is this seen?
merocrine
seen in the salivary glands and pancreas
