S7- membranes Flashcards
1
Q
functions of cell membranes include:
A
- functional barrier- compartmentalization of cells
- provide cells with energy (chemical and charge gradients ie: electron transport chain)
- organise and regulate enzymes
- facilitate signal transduction
- supply substances for biosynthesis and for signalling molecules
- protein recruitment platfom
2
Q
3 main lipids that make up cell membrane are:
A
- glycerophospholipids (phospholipids)
- Sphingolipids
- sterols
3
Q
most lipids are…(have hydrophillic/ head and hydrophobic/ tail regions)
A
amphipathic
4
Q
fatty acids can be…or…
cis double bonds make…
trans double bonds make…
A
saturated lipid tails= no double bonds- chain is relatively straight
unsaturated= 1+ double bonds- 2 types
cis= 30 degree kink/ twist
trans= doesnt affect structure/ straight
5
Q
glycerophospholipids have 3 parts:
fatty acid linkage is called…
A
- head group (phosphate+ alcohol)
- glycerol backbone (triol= each OH group is numbered 1-3)
- acyl chains/ 2 fatty acid chains
Ester/ acyl (OH from glycerol and fatty acid form H2O- esterification)
6
Q
sn-1 fatty acid (on first OH of glycerol) is usually…
Sn-2 fatty acid is usually…
A
saturated or monounsaturated
monounsaturated or polyunsaturated
7
Q
the basic structure of the membrane glycerophospholipids is called…
the rest of the phospholipids are derived from it, the phosphate group is further…
A
phosphatidic acid/ phosphatidate
esterified tot he hydroxyl group of one of several acohols (serine S, choline C, glycerol G, ethanolanime E, inositol I)
8
Q
the anionic phospholipid are…and they have a net…
A
PS, PI, PG, CL (cardiolipin)—> they have more O- then positive charges (NH3+)
negatie charge
9
Q
zwitterionic phospholipids have…
A
zero charges
10
Q
PS and PE contain reactive…that can participate in…
A
Amines
hydrogen bonding
11
Q
PI, PC, and CL are relatively…which affects their…
A
bulky
packing
12
Q
some phospholipids are…specific
Ie: PG and CL are only found in the…
A
organelle
mitochondria
13
Q
sphingolipids are built on 3 parts:
A
sphingoid base backbone, N-acyl (fatty acid) chain, head group (phosphate and another molecule attched to backbone)
14
Q
N-acyl chains of phospholipids tend to be more…and…in sphingolipids than in glycerophospholipids
A
saturated
longer
15
Q
N-acyl chain is attched via…in sphingolipids and the other amide group has the ability to form…(to allow interaction with cholesterol or polar parts of protein)
A
amide linkage
H bonds
16
Q
the most common sphingolipid is…and it has a…head group
A
sphingomyelin
phosphocoline
17
Q
glycosphingolipids have different…as head groups and are found exclusively in the…of the membrane and make around…% of that layer
A
oligosaccharides
outer lealflet of the membrane
5%
18
Q
glycosphingolipids are exposed at surface membranes because it has an important role in…and allows membranes to act as….for certain chemicals
A
Cell-cell adhesion
recognition sites
19
Q
sterols structure has…
A
4 fused rings (tetracyclic), hydroxyl group on A ring and a hydrocarbon tail (attached to last ring)
20
Q
…is the most common sterol in animals
….is found in yeast and fungi
….and…are found in plants
A
Cholesterol
ergosterol
Sitosterol and stigmasterol
21
Q
the size and shape of cholesterol allows it to…
its presence increases…and decreases…
A
interact with pockets in membrane proteins
thickness, packing, compressibility
mobility/ flexibility of lipids and proteins
22
Q
in water, lipids bury their… in the interior and expose their….to water
They create a…or..shape
A
hydrophobic tails
hydropholic heads
Bilayer or micelles
23
Q
3 types of membrane curvature are:
A
- cylindrical lipids= flat membrane (PC, PS)
- conical lipids= negative curvature (PE, acid)
- inverted-conical= positive curvature (PI)
24
Q
membrane curvature is determined by…
negative curvature leads to…properties which might rpomote processes that involve…
A
relative sixe of head group and hydrophobic tails of lipids
Bilayer-disrupting
generation of non-bilayer membrane intermediates such a fusion
25
lipid asymmetry is…
-phosphatidylserine translocates to the…which cell undergoes apoptosis to act as…to macrophages to...
functionally important
extracellular monolayer
signal
come and digest it
26
glycolipids are oriented towards the…for cell-cell adhesion
second messengers in signalling pathways are oriented towards...
exterior of cell
the interior of cell
27
lipids in bilayer move with 3 different movements:
1. Rotational: spinning of lipids around its axis (doesnt alter its position but affects interaction with neighbouring cells)
2. lateral: neighbouring lipids exchange places= allows to change position within a bilayer leaflet
3. Transverse: exchange of molecules between leaflets (move across bilayer) by transverse diffusion or mediated by proteins (unidirectional or bidirectional)
28
protein-mediated transverse lipid translocation may need…
some proteins are non-specific while other only translocate..
energy input (ATP)
specific lipids
29
3 types of proteins that translocate membrane lipids:
1. P-types flippase: need ATP+ carry out inward movement of lipids+ specific
2. ABC flippase: need ATP+ carry out outward movement of lipids+ specific
3. scramblase: no ATP+ bidirectional, non-specific+ Ca2+ dependent
30
the fluid mosaic model emphazises the…
the bilayer is fluid due to…
it is mosaic because...
fluidity of the bulk of lipids allowing random diffusion
lateral mobility of lipids and some proteins
proteins are scattered across it
31
there is some…organisation in membranes
The concept of membrane….or…which are enriched in…and…
proteins are either exculded or included in the raft regions
lateral
domain or rafts
Cholesterol and sphingomyelin
32
lipid rafts are expected to be different in their...
lipid composition, lifetimes and sizes
33
3 types of membrane proteins are:
1. integral (intrinsic)
2. Lipid-linked
3. peripheral (extrinsic)
34
5 functions of integral membrane proteins:
1. trasnport (move molecules by changing shape)
2. enzymatic activity (electron transport/ metabolism of phospholipids and sterols)
3. signal transduction (after ligand/ molecule binding)
4. Cell-cell interactions (glycoproteins= short-lived cell interaction)
5. attachment to cytoskeleton or the extracellular matrix
35
integral proteins can be non-covalently bound to... in cell’s cytoskeleton
this can regulate cell…or stabilise…
they can also bind to extracellular matrix which facilitates...
proteins
Shape
protein position in the membrane
cell-cell adhesion
36
4 examples of integral proteins:
1. Glycophorin A (1st integral protein to be sequenced)
2. bacterio-rhodopsin (1st integral protein whose structure was determined)
3. glucose transporter (GLUT)
4. ion channels
37
GLUT is found in nealry all cells and is abundant in…
the membrane spanning region is composed of…
glucose binds to…surface site and causes a…
glucose is released at the…side of the membrane into the...
cell lining the small intestine
12 a-helicases
outer
confrontational change (of shape)
inner
internal aqueous solution
38
Bacterio-rhodopsin has….helices with short loops on…
it has…amino acids in an…
it is made of multiple transmembrane…packed in a bundle
7 transmembrane
either side of the membrane
20-30
alpha helix
Domains
39
ion channels do not require…changes unlike…
there is a…variety of channels and they are…
channels can open in response to…(6 things)
large confrontational
transporters
wide
selective
ligand binding, electric potential, pH, temperature, pressure, lipids
40
perioheral membrane proteins bind to…
they interact with…lipid headgroups or…or both
they also interact with…chains
surface of the membrane
anionic
charged groups on proteins (ie:integral proteins)
hydrophobic lipid acyl
41
Lipid-linked membrane proteins are…linked to a lipid which is..in the membrane
different proteins use…for attachments
covalently
inserted
different lipids
42
2 ways peripheral proteins can bind to the membrane
1. lipid linked
2. positively charged surfaces (to anionic lipids)
43
often proteins bind to…lipid chain as one is not sufficient for binding
Myristoyl (lipid) groups are connected to…
Palmitoyl (lipid) groups are…linked to…or...
more than one
glycine residue
covalently, cystine or serine residues
44
mutations of myristoyl and palmitoyl sides result in…
glycosylphosphatidylinositol (GPI) anchor is a...
loss of binding pf pertipheral proteins
Post-translational modification that anchors a modified protein in the outer leaflet of the cell memebrane
45
carbohydrates in the cell membrane are attached to:
they are located in…face of membrane
1. Lipids: glycolipids
2. Proteins: glycoproteins
Extracellular
46
glycoproteins are important because they:
2 types of glycoproteins:
- stabalise proteins
- cell-cell recognition
1. O-linked (linked to oxygen atom in side chain of serine or threonine)- 2-5 sugars= short
2. N-linked (linked to amide nitrogen in side chain of asparagine amino acid)- large branched structure as many as 30-40 sugar residues
47
an asparagine residue can accept an…of it is part of an….sequence
Oligosaccharide
Asn-X-Ser or Ash-X-Thr (X is any residue)
48
small molecules can cross cell membrane through:
1. passive diffusion (simple or facilitated)
2. active transport (ATP/ ion driven)
49
Macromolecules can cross cell membrane through:
1. exocytosis (organised/ constitutive/ regulated)
2. endocytosis (phagocytosis/ Receptor-mediated/ pinocytosis)
50
membranes are..and maintain a…environment
internal organelles often have different….to..
selectively permeable
constant internal
different environment to cytosol (ie: lysosomes= pH less than 5)
51
simple diffusion includes diffusion of...
Gases and hydrophobic molecules and small polar molecules
52
facilitated diffusion depends on…
the proteins are…and depend on...
integral membrane proteins (carriers, permeates, channels, transporters)
specific
temp, pH, saturable, inhibitable
53
2 facilitated diffusion carrier examples:
1. ionophore= ion carrier (produced by bacteria as antibitics against other competing bacteria= to ds=ischarge ion gradient of target cell)
2. ion channels= rapid and gated passage of anions and cations and highly selective
54
ion channels are essential for:
1. maintaining osmotic balance
2. signal transduction
3. nerve impulses
55
2 types of ionophores: (both integral proteins)
1. carrier= ie: valinomycin - specific to K+ ions
2. Channel-forming= ie: gramicidin A - monocovalent cations ie: Na+ and K+
56
different families of ion channels include:
1. voltage-gated (Ca2+/ Na+/ K+)
2. Non selective cation channel
3. Ca2+ activated K+ channels
57
2 specific exaplmes of facilitated diffusion:
1. glucose transporter (GLUT)= into and from blood
2. Aquaporine= transmembrane protein that filtrate, absorb and secrete fluids
58
3 trypes of integral protein transporters for active transport:
1. uniport= one specific molecule + one direction
2. symport= 2 molecules in SAME direction (one direction)
3. antiport= cotransporter ie: Na+/H+ and pH regulation= 2 molecules in 2 directions
59
ATP driven active transport transports against…
and need energy through...
Conc or electrochemical gradient
ATP hydrolysis
60
ion driven active transport uses the energy stored in the…
secondary active transporter that transport of a molecule is coupled to the…
electrochemical gradient
movement of an ion
61
movement of molecule in ion driven active transport is coupled with…
example of symport:
example of antiport:
Na+ or H+ movement
Na+/ glucose transporter
Na+/ Ca2+ exchange
62
exocytosis is:
1. Constitutive:
2. Regulated:
- all cells, secreted proteins and plasma membranes
-specialised cells (neuronal, pancreatic), Ca2+ dependent= ie: in nerve terminal
63
3 types of endocytosis and their examples:
1. phagocytosis= ingestion of large particles (bacteria/ debris) by specialised cells
2. Pinocytosis= uptake of fluids “cell drinking”
3. receptor-mediated= cholesterol/ LDL-R
64
phagocytes are found in…
Examples:
steps in engulfing:
immune system
Macrophages, neutrophils, dendritic cells
1. pseudopodia (temporary arm-like structure that wraps around the pathogen)
2. pathogen in vacuole + lysosome joins
3. phagolysosome forms
4. antigen presentation
65
receptor-mediated endocytosis is good for contracting…of macromolecules
it is selective and it involves...
low levels
Clathrin-coated pits and vesicles
66
steps in receptor-mediated endocytosis:
Example:
1. ligand binds to receptor
2. coated vesicle forms (ligand and recpeotr together) + endosome joins= fuse together
3. lysosomes join+ lysosomal degradation occurs
4. receptors recycled
cholesterol uptake by LDL receptor (can be exploited by viruses to gain entry to cells)
67
how do GLUT transporters work:
1. 3 Na+ out from epithelial cell into blood and 2 K+ in (high Na+/ low K+ in blood)
2. low Na+ conc inside cell and high K+ inside cell
3. 2Na+ and glucose from lumen (high Na+) into cell (symporter driven by high extracellular Na+)
4. glucose uniporter (GLUT2) facilitates glucose transport from cell into blood
68
Aquaporins/ water channel proteins are requied for…
it is called:
it is a…and aabundant in erythrocytes, kidney cells
Bulk flow of water actoss cell membranes (singular water molecules dont need it)
28 kDa, 6 transmembrane alpha-helices
Tetramer with 4 pores
69
Na-K-ATPase transporter is…
high K+ and low Na+ in cell=…
it helps:
ATP driven
Na+/K+ gradient (maintained by Na+/K+ ATPase)
1. control cell volume
2. makes nerve and muscle cells electrically excitable
3. Facilitates ion-driven active transport if amino acids and sugars
70
Na+/K+ transporter pumps…which…the cell membrane
ATP hysrolysis includes…to pump the ions against their conc gradient
…system: ATP is not hydrolysed unless...
3 Na+ out and 2 K+ in
polarises (+ on outside= important for pathogen protection)
confrontational changes
coupled system
Na+ and K+ are transported and vice versa
71
cardiac glycosides/ cardiotonic steroids (are now replaced by…)
they are used in…
they are made of…steroids
the inhibit…which...
ACE inhibitors and diuretics
congestive heart failure (heart fails to pump blood around body)
plant
inhibits Na+/K+ ATPase
-increase Na+ conc in cell and decrease it across membrane
-decrease Ca2+-Na+ exchange
-increase Ca2+ conc in cell
-enhance strength of contraction of heart muscle
72
oral rehydration therapy is…
it increases…pressure in..cells
it is used in…to treat...
a type of fluid replacement used to prevent and treat dehydration
osmotic pressure
epithelial cells
developing countries to treat cholera, diarrhoea etc
73
oral solution given as rehydration therapy contains…
Glucose uptake is dependant on…
water, glucose, Na+, k+
Na+ (therefore both are included in the solution)
74
Cholera:
- symptoms
- prevalence
- cause
- treatment
- severe diarrhoea, vomiting
- 3-5 mill causes a year/ more than 100,000 deaths
- vibrio cholerae bacteria in contaminated water and food/ virulence factor= cholera toxin
- oral rehydration (water, salts, glucose)
75
cell signalling is a process of cellular…
it allows cells to:
communication
- regulate development and organise into tissues
-control their growth and development
-co-ordinate functions
-respond to their environment
76
most drugs work by targeting…of cell signalling
this is important to understand:
one step
-efficacity
-interactions
-specificity (side effects)
77
4 types of extracellular signalling:
1. autocrine: a cell targets itself
2. Endocrine: a cell tagets a DISTANT cell through circulation/ blood
3. juxtacrine: cell targets a neighbouring cell via direct contact (ligand, receptor, GAP junction)
4. Paracrine: a cell targets a neighbouring cell
78
Autocrine signalling is….in most cancer cells because it is involved in signal…
2 types:
dysregulated
signal amplification (+ve feedback)/ attenuation (-ve feedback)
Self-stimulation and trans-activation (need another molecule to be added to help activation)
79
example of endocrine signaling (most hormones)….
example of paracrine:
examples of juxtacrine:
glycemia (conc of sugar/ glucose in blood)
synapric
antigen presentation and cardiac contraction
80
extracellular signalling cells are…
for example:
1st messengers
growth factors, neurotransmitter, hormones (endo/ para), cytokins
81
4 main classes of receptors:
1. Ligand gated ion channel
2. G-protein coupled receptor (GPCR)
3. Kinase-linked
4. Nuclear receptor (inside cell- while the pther three are on membrane)
82
ligand gated recepors are also called:
they open and close...
example:
other examples: GABA, GlyR, 5-HTR
ionotropic receptors
very fast= 2mlsec
nicotinic acetylcholine receptor (nAChR)= Na+ in and K+ out = depolarisation
at neuromuscular junction= muscle contraction
83
GPCR is also known as…
it is the largest family of receptors
it is…than ligand linked
it is coupled to….
metabotropic (2nd messenger couples) or 7 transmembrane spanning (7TM) receptors
slower
Intracellular G protein (3 subunits)= activated when ligand binds to receptor= bind with GDP
84
examples of GPCR: (variety of stimuli: light/ hormones/ neurotransmitter)
adrenoreceptors
(Muscarinic Ach and angiotensin II= other 2 examples)
85
kinase-linked receptors are…receptors
they use…to add…group to substrate
it is a large and heterogenous group, has…transmembrane domain
mostly function as…
Kinase ligand and dimerisation leads to...
catalytic
kinase, phosphate
One
dimers
phosphorylation
86
examples of kinase-linked receptors:
1. catalytic (hormones/ GF)= autophosphorylation (insulin receptor)
2. non-catalytic (cytokines)= IL-2, IL6
87
Nuclear hormone receptors are…receptors
it is a…structure
they regulate…transcription
intracellular (in sytosol or nucleus)= ligand activated transcription factors
monomeric (seperate ligand and DNA binding domains)
Gene
88
2 examples of nuclear receptors:
1. Steroid hormones
2. thyroid hormones
89
signal transduction is when...
extracellular signals are converted into intracellular signals
90
example of cell transduction: (adrenaline)
terget cell= liver or skeletal muscle
recpetor= beta-adrenergic receptor
Response= break down of energy reserves (glycogen) to glucose
91
steps in cell transduction:
1. 1st messenger (ligand)
2. bond with GPCR
3. G protein activated
4. effector enzyme (adenylyl cyclase)= ATP
5. 2nd messenger= cAMP
6. protein kinase A= adds phosphate to protein
7. terget protein (phosphorylated protein
8. cellular response
92
2nd messengers are….
they have a…increase in conc after stimulation
they need to be…
some can also be...
short-lived signalling
Quick
transient (temporary)
primary messengers depending on hierarchy of events (orderly manner)
93
4 classes of 2nd messengers:
1. cyclic nucleotides (cGMP, cAMP)
2. membrane lipid derivatives (DAG)
3. Ca2+
4. Gas (nitric oxide, CO)
94
circulating molecules conc ned to remain…so receiving cell…the signal
low
amplifies
1st messenger-> several activated target protein
95
pathway for signal transduction are…and...
specific and complex
96
main types of lipids in the body are:
1. triglycerides
2. Cholesterol
3. phospholipids
4. steroids
97
lipoproteins transport…
they share a…structure but different ratios of…
they are classified according to...
insolube cholesterol and triglyceride in blood plasma
General
Protein:lipids
density and chemical properties
98
4 types of lipoproteins
1. chylomicrons (biggest) (VLDL and their catabolic remnants)= produced in intestine
2. VLDL= produced in liver
3. LDL=
4. HDL (smallest)
99
