Cell Processes Flashcards
Fluid Mosaic Model
50% lipid, 50% protein held together by H-bonds
Lipid is the barrier for entry/exit of polar substances
Proteins regulate traffic
What is membrane fluidity determined by
Lipid tail length - the longer the tail, the less fluid the membrane
Number of double bonds – more double bonds increases fluidity
Amount of cholesterol – more decreases fluidity
Integral membranes (INTRINSIC)
- How is located in membrane?
- What are the regions and what do they do?
Extend into or completely across membrane
Amphipathic
Hydrophobic core- coiled helices of non-polar amino acids
Hydrophilic end interacts with aq. solution
Peripheral proteins (EXTRINSIC)
- how does it interact?
- What removes it?
- how is it attached?
Attached inner or outer surface of CM
Easily removed by detergents- break H-bonds
Indirectly bound- attach to integral proteins
OR
Interact w/ lipid polar head group
Example of Peripheral protein and its importance
Cytochrome C
Essential in ETC, links complex 3 and 4
How can peripheral proteins be disrupted?
Change in pH or salt concentration
What can membrane proteins act as?
Receptors, Cell ID markers, Linkers, Enzymes, Channels, Transporters
Every triathelete really loves cutting corners
Lipid bilayer permeable to
Uncharged non-polar- O2, N2, benzene
Small uncharged polar- water, urea, CO2, glycerol
Lipid soluble- Steroids, fatty acids, some vitamins
Lipid bilayer impermeable to
Large uncharged polar- Glucose, amino acids
Ions- Na, K, Cl, Ca, H
Diffusion
- what factors give faster diffusion
- when is diffusion fast
High-> low conc.
Greater diff. between two sides of membrane, High temp, high SA, small size, shorter diffusion distance
INCREASE RoD
Fast only across short distances
What is the size limit for diffusion?
20 um
What are the two gradients across a cell membrane?
Conc. gradient
Electrochemical gradient
Conc. gradient
- Definition
Non-charged molecules, DOWN conc. gradient
Electrochemical gradient
- what ions are high in and outside cell?
- what direction and how do they travel
“Salty banana”
High Na, Cl outside
High K inside
So ions travel to lower side. diffuse down con. grad
What do conc. and electrochemical gradients represent?
Stored energy
Osmosis
- Defintion
- what is colligative property?
Diffusion of water across semi-permeable, high to low
Depends on number not types of particles in solution
Osmotic pressure
Pressure applied to prevent osmosis
E.g. more water on one side of membrane as it has more solute
Isosmotic definition
Solution has same osmolarity compared to reference solution
Hyposmotic definition
Lower osmolarity than reference solution
low solute conc.
high water conc.
Hyperosmotic definition
Higher osmolarity than reference solution
high solute conc.
low water conc.
What is the osmolarity of body fluid?
- what occurs when osmosis occurs?
280 mOsmol
Change in cell volume occurs if osmosis occurs
Tonicity
- definition
Effect of cell volume due to solution
only influenced by cells that can’t cross semi-permeable membrane
Isotonic
No change in cell volume
Hypotonic
Swelling, lysis (haemolysis- rupture of RBC)
Hypertonic
Cell shrinkage (crenation)
What do membranes mimic?
- what can they store
Capacitors
Can separate and store charge
Width of bilayer membrane
8 nm (8x10^-9 m)
Glycolipid
- location
- function
Attached to membrane
Cell recognition, maintain stability
Glycoprotein
- what type of membrane protein is it?
- function
Intergral membrane protein- have carbohydrate branching off coiled a.a membrane
Cell to cell recognition
Water permeability in relation to membrane fluidity
More fluid= higher lipid-water permeability
What are the two ways water can cross lipid bilayer
Diffusion
Aquaporins
What is more permeable to water, aquaporin or diffusion through lipid bilayer
Aquaporin > lipid bilayer
Pf > Pd
What are the properties of water moving through lipid bilayer?
Its small,
Isn’t blocked by mercury (mercury- binds to proteins causing changes)
Temp. dependent (lipid fluidity)
What are the properties of water moving aquaporins?
Large
Mercury sensitive- mercury can bind to proteins in channels and block them- aquaporin can be inhibited
Temp independent
How many isoforms of aquaporins are there in human genome?
9
Expressed differently in different cells
Why can cells express different Pw?
Express different aquaporin isoforms
What is the osmotic gradient?
What is the permeability of membrane to water?
Difference between osmolarity and tonicity
osmolarity is difference in solute conc. and tonicity is the movement of solute which also brings movement of water
E.g. urea moves into RBC, and
What causes change of shape in carrier protein
Hydrolyses of ATP, Phosphate group binds to carrier protein causing ‘flipping’ mechanism
Secondary Active Transport
Uses energy from one solute moving down its conc. grad, and in return the energy given off from this is used to transport another diff. solute AGAINST its conc. gradient
Antiporter (secondary)
Is a co-transporter
Transporting 2 different molecules across CM in opposite directions
Symporter (secondary)
Co-transporter
Transport 2 different molecules across CM in SAME direction
Pump-leak hypothesis
Na+ continuously leaking out & K+ in
Pump works continuously
Tight Junctions
- act as…
Separate epithelial cells by lateral intercellular space
Barrier- restrict movement of substances through intercellular space between cells
Fence- prevent membrane proteins from diffusing in plane of lipid bilayer
Held together by luminal edges of tight junctions
Apical membrane
Luminal/Mucosal
Faces lumen of organ or body cavity
Basolateral membrane
Adheres to adjacent membrane and interfaces with blood
Paracellular Transport
Transport across epithelium by passing through intercellular space
Transcellular Transport
Substances travels through cell passing apical and basolateral membrame
create ion/conc. gradients that can drive paracellular
2 types of transcellular transport
Absorption: lumen to blood
Secretion: blood to lumen
Changes in tight junction resistance
Proximal –> Distal direction in GI and kidney
Patch clamp technique
Seal off one ion channel, can monitor particular channel, see how it changes shape
What do current fluctuations represent
Opening and closing of single ion channels
Conformational change in channel structure associated with channel gating
Carrier mediated transport exhibit..
Specificity
Inhibition
Competition
Saturation (max. transport)
Facilitated diffusion of glucose
Glucose binds to GLUT
Transporter protein changes shape. Glucose moves down conc. grad
Kinase enzymes reduce glucose conc. inside cell by converting glucose into glucose-6-phosphate
What does the conversion of glucose do for cell
Maintains conc. gradient for glucose entry
Paracellular tight junctions
Higher electrical resistance to ion flow = greater no. of tight junction strands holding cell together
Leaky epithelium
Paracellular transport dominates
Tight epithelium
Transcellular transport dominates
SGLT
Na-gluose Symporter transporter
Secondary AT
Carrier-mediated
GLUT
facilitative glucose transporter mediates glucose exit acorss basolateral membrae
Passive diffusion
Pump-leak hypothesis for glucose absorption
Na+ enters cell by SGLT down grad. as more Na+ inside cell
as hypothesis states, Na+ needs to leave and it leaves by Na/K pump in basolateral
Pump-leak hypothesis for glucose absorption
Na+ enters cell by SGLT down grad. as more Na+ inside cell
as hypothesis states, Na+ needs to leave and it leaves by Na/K pump in basolateral
What is the last step in glucose absorption in SI
Cl and H2O via paracellular pathway from lumen into blood as Na+ ve draws -ve ion,
How does glucose leave cell into blood
Travels down conc. grad. (cell) to low conc. (blood) facilitated diffusion through GLUT
Oral rehydration therapy
Sugar solution containing glucose, increases absorption of Na+, thus Cl- and water
Glucose-galactose malabsoprtion syndrome
genetic defect in SGLUT mutated, cant take up glucose
Sugar retained in intestine lumen
Consequences of GGM syndrome
Glucose comes in broken down into, more particles mean higher osmolarity
Osmosis into lumen Water chyme (diarrhea)
How to treat GGM syndrome?
Replace glucose in diet with FRUCTOSE, GLUT5 facilitative transporter
Glucose Reabsorption in kidney
Glucose reabsorbed by SGLUT in lumen, then facilitative diffusion into blood
What happens if SGLUT not functioning fast enough
Glucosuria- glucose in urine as it can’t be absorbed fast enough
DIABETES MELLITUS
- insulin activity deficient and blood sugar too high (>200mg/ml)
When does glucose appear in urine?
When renal threshold reached @ 200 mg/100 ml plasma
Transport maximum of SGLT reached 375mg/min of glucose
What form of transport is glucose in kidney
Carrier mediated transport- all transporters used up
secondary AT
Chloride secretion
1) Tight junction divides apical and basolateral membrane
2) Na/K pump sets up ion gradient (primary AT, electrogenic)
3) NaK2CL symporter uses energy of Na gradient to accumulate chloride above electrochemical gradient, so Cl- wants to leave cell now
4) Cl leaves cell by passive diffusion through Chloride ion channel
5) Na exits via basolateral Na-pump and via K+ via channel
6) Lumen now -ve, so Na+ and H2O moves paracellular down conc. grad into lumen
Rate limiting step
Cl- can’t leave cell unless channel open
Opening of Cl- channel gated
Channel called CFTR
CFTR
Cystic Fibrosis Transmembrane conductance Regulator
Consequence of over stimulation of CFTR and
Secretory diarrhea and its dysfunction causes cystic fibrosis
How is secretory diarrhea caused and what causes this excessive stimulation
Excessive stimulation of secretory cells in crypts of small intestine and colon
Excessive stimulation due to abnormally high conc. of endogenous secretagogues produced by tumours or inflammation
Secretagogue
- where do they bind to
substance that promotes secretion, NA and ACh
bind to GPCR, which releases a G-protein
G-protein binds to adenylate cyclase, releasing cAMP
cAMP activates Protein Kinase A which sticks a phosphate onto CFTP on apical membrane, staying open
Enterotoxin
- what does it do in secretory diarrhea
toxin affecting intestines
vibrio cholerae
Difference between normal mechanism and mechanism of cholera
Instead of G-protein binding to Adenylate cyclase cholera toxin binds irreversibly to Adenylate cyclase
How to treat secretory diarrhea
Give them glucose/electrolytes
What happens to cells of crypts after 5 days
The crypts cells move up villus changing from secretion cells to glucose absorption cells @ top of villus
Cystic fibrosis
Inherited disorder affecting children and young adults
Autosomal Recessive= chromosome 7
1/4 chance
Which ethnic group is CF most common
Northern Europe
1: 2500 CF
1: 25 carriers
Organs affected by cystic fibrosis
airways- infection bronchial passages, lung cancer
liver- plug small bile ducts
pancreas- prevent digestive enzymes delivered to bowel
small intestine- thick stool blocks gut
reproductive tract
skin- salty sweat
Events in CFTR
Secretagogue had to bind, activate cAMP, activate protein kinase A, phosphorylate Regulatory domain
ATP binds to Nucleotide binding domain (NBD)
How to shut the CFTR channel
Hydrolyse ATP to ADP and P
How to permanently close channel
Dephosphorylation
Lung epithelial cells in CF
Defective Cl- channel prevents isotonic fluid secretion
Enhances Na+ absorption to give dry lung surface
Clinical treatment of CF
Chest percussions improve clearance of infected secretions
Antibiotics
Pancreatic enzyme replacement- pill before eating for digestion 6
two stages of sweat
Primary isotonic secretion fluid by acinar cells
secondary reabsorption of NaCL but NOT water produces hypotonic solution
What is the difference in CF patients producing sweat
Epithelial cells in ducts of sweat glands don’t absorb NaCl and thus producing salty sweat
