2. Membranes and Transport I Flashcards by J L

Membrane function

____ barrier
Keep external components out of cell interior
Retain cell constituents

____ control
Selectively control entry and exit

permeability

border

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Membrane structure

Fluid mosaic bilipid membrane - mix of ____ and ____
Not just proteins bobbing in sea of lipid
Both lipid and protein arrangement highly ____

• Half of surface area - ____, that are highly structured

lipids
protein
structured

proteins

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Lipid bilayer is amphipathic Amphipathic: both ____ and ____ portions

With phospholipids, only heads stable next to ____ - bilayer

Energetics - most ____ arrangement for these phospholipids
Occurs ____

polar
nonpolar
water
favorable
spontaneously

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Membrane fluidity varies

Membrane fluidity influenced by distribution of ____
____, length and ____ of fatty acid chains decrease fluidity
____: Clusters of cholesterol, proteins sphingolipids

lipids
cholesterol
saturation
rafts

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Rafts cluster signaling proteins

Many signaling processes require multiple players
Rafts provide island to cluster key ____ together receptors/enzymes, internalization with ____
Multiple cellular processes require ____

____ is important when it comes to activation via NT Necessary to optimize chances of achieving the signal we need

signalling components
caveolae
proximity

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Lipid rafts relevant to dentistry

• Membrane vesicles (MVs) from ____ enter human gingival epithelial cells more when ____ intact

P. gingivalis

lipid rafts

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P. gingivalis enters cells via lipid rafts

• Suggest entry via raft allows bacteria to evade ____ more readily

digestion

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Membrane lipids summary

Lipid molecules are ____: they have a hydrophilic polar component and a hydrophobic non- polar tail
Lipids are ____ distributed on the outer and inner leaflets of the membrane
Membrane fluidity varies with ____ content and degree of ____ of fatty acid chains; key proteins for many signaling processes are clustered in ____

amphipathic
asymmetrically
cholesterol
saturation
rafts

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Membrane proteins

Critical to how we control processes across the membrane
____ = gap junction protein

connexin 26

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Classes of membrane proteins

Integral proteins - span ____
Peripheral proteins
- restricted to one ____
- ____ within membrane or ____ to membrane lipids

• Optimize ____ that occurs across membrane

bilayer
side
move
anchored

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Functions of membrane proteins

____ (pumps/carriers/channels)
Structural - anchors etc maintain membrane integrity
Receptors/signaling
Enzymes
____ – antibody recognition

Transport

glycoproteins

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Transport membrane proteins

• Transporters
◦ Make sure that ____ compounds get
across the membrane
◦ Allows ____

charged/uncharged

selectivity

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Types of membrane transport How to get across the membrane?

____ across bilayer
Facilitated diffusion
- ____
- ____
Active transport
- ____
- ____

• Active
◦ Direct/indirect requirement for ____ against gradient
• ____
◦ Simple
◦ Facilitated
‣ ____ used to aid diffusion (channel mediated
and carriers)

diffusion
channel
carrier
ATP
passive
proteins

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Transport across membranes
• Cell membranes are selective, semi- permeable barriers
• Molecules move across cell membranes by
– Simple diffusion
• Follows \_\_\_\_ gradient
– Facilitated diffusion 
• Follows \_\_\_\_ gradient
– Active transport
• Uses energy to go \_\_\_\_ EC* gradient

EC
EC
against

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Diffusion

• Process whereby molecules move and intermingle because of ____ motion

random thermal Brownian

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Fick’s First Law of Diffusion

Diffusion across a membrane is proportional to:

____ of membrane (involved in diffusion)
difference in ____ on the two sides

J = -DA(∆c/∆x)
where:
J - net rate of ____ in moles or grams/unit time;
D - diffusion ____ of the solute;
A - ____ of the membrane;
∆c - ____ difference across the membrane;
∆x - membrane ____
D – inversely proportional to ____ of particle and ____ of solvent (big globs move slowly through thick muck)

area
solute concentration
diffusion
coefficient
area
concentration
thickness
size
viscosity

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A note on equations: Equations can only describe ____ processes

A bit of understanding goes further than straight memorization
Qualitative understanding of diffusion and osmosis equations Quantitative understanding of Nernst and GHK equations

simple

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What about crossing the membrane? The same laws apply J = -DA(∆c/∆x)

Diffusion of a solute through a cell membrane depends on:
– membrane ____ - ∆x
– ____ difference - ∆c
– ____ of membrane - A
– ____ and ____ of solute (lipid solubility) - 1/D – ____of solvent -1/D

• Big difference is that small uncharged molecules much more ____ in lipid bilayer
• The more charged and larger you are, the more difficult to cross the membrane
◦ Preference for uncharged
• More ____ - more difficult to diffuse

thickness
concentration
area
size
charge
viscosity

soluble
viscous

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Effective range of diffusion
– Diffusion time ____ with the ____ of distance

Diffusion fine for very ____ distances (cell ~ 10 um dial)
Need other forces to move further in reasonable time: nervous and circulatory system

increases
square
short

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Permeability across membrane

Dependent on 
• \_\_\_\_
• charge
• \_\_\_\_ solubility
• membrane thickness

O2, CO2, N2 - ____ and small, travel across the membrane quickly
H2O - ____
Glucose - ____
Ions - ____ charge, do not cross the hydrophobic barrier too well

size
lipid
uncharged
polarized
size
positive

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How do compounds cross mucosal membrane in oral cavity?

Diffusion via ____ pathways
Barriers you will have to use ____

paracellular

transport

Facilitated diffusion:
Transport across membranes with a little help from the ____
• Many large and/or charged molecules cannot diffuse across the bilipid membrane
• Specialized proteins aid in the crossing
• Transport called facilitated diffusion if proteins provide a ____ through membrane to avoid lipid barrier
•____ transport
- ____
- ____

proteins
route
passive
carriers
channels

Facilitated diffusion
• Diffusion of a solute mediated by carrier proteins
– via ____ conformational change
• Solutes move down their ____ gradients
– no exogenous ____ required
• Enzyme that transports across membrane
• Unlike simple diffusion, facilitated diffusion can reach a ____, ____ – carrier as enzyme
• Facilitated diffusion exhibits
– ____ specificity
– ____
– ____ inhibition

• Presence of enzyme kinetics:
◦ ____ - how fast
◦ ____

ping-pong
electrochemical
energy
maximum (Vmax)
Km
chemical
sterospecificity
competitive

Vmax
Km

Saturation of facilitated diffusion

The carrier protein can only ____ so quickly > formation of a Vmax

flip-flop

Facilitated diffusion by ion channels Ion channels: – Ions flow through the pore – “downhill” so no exogenous ____ required – ____: many roles in rapid signaling – Conformational change to gate open triggered by ____, ____, ____, – ____ varies – More details tomorrow

``` energy fast voltage ligands stretch selective ```

What ion channels are targets in dentistry? • ____ channels ◦ Lidocaine blocks these • ____ channels ◦ If patient's are on blockers, may interfere with ____

sodium potassium heart

Active transport • Active transport expends ____ to move solutes “uphill” against gradients and keep ions from ____ • Requires energy input – Primary active transport uses ATP (____) – Secondary active transport couples energy from ____ • Transporter has properties of carrier protein – ____, ____

``` energy equilibrium ATPases gradients Vmax stereospecificity ```

Primary active transport Na-K-ATPase * Transport of ions against ____ * Uses ____ of cell ATP - critical to function * Found in all ____ cells * Electrogenic – 3 ____+/2 ____+ drives a net charge across membrane (only ____ mV) * Main role is to set up ____

``` gradient 33-70% animal Na K 2-4 gradients ```

Half of your food goes to power the ____

Na/K ATPase

Model for operation of the Na+-K+ ATPase pump 1. Binding of 3 ____ inside 2. Hydrolysis of ____ for energy 3. Release of ____ outside 4. Binding of 2 ____ outside 5. ____ 6. Release of ____ inside Energy is used to pump Na+ and K+ against their gradients * Binding of ATP occurs after binding of three Na+ ions * Binding of K+ triggers the ____

``` Na+ ATP Na+ K+ dephosphorylation K+ ``` dephosphorylation

Ouabain blocks the Na-K ATPase * Ouabain – digitalis ____, selective for ____ pump, * Ouabain binds ____ side * Used clinically to slow ____ when troubled e.g atrial ____ * Now use related ____ * Don’t use too much word ouabain from Somali “waabaayo “ translated as “____”

``` glycosides Na/K extracellular heart fibrillation digoxin arrow poison ```

Active transport pump H-ATPase * Complex multisubunit structure * ____ portion that hydrolyzes ATP into ADP * ____ portion uses this energy to move H+ across gradient * Uses energy of ____ to transport protons against their gradient * Useful in building ____ and ____ * Used in ____ * Changes the proton gradient; pushes H+ against their gradient

V1 V0 ATP bone teeth lysosomes

H-ATPase * vH-ATPase present in intracellular ____ * H-ATPase is also present on ____ in some cells * Important in bone ____ * Blocking H-ATPase with ____ inhibits tooth eruption * Mandibular and maxillary ____ and molars are not present in Atp6i-/- mice. • Makes areas more acidic - important in bone degradation • Changes in AA structure can lead to differences in the enzymes function --- Some may have no ____ --- Some may result in stark ____

``` organelles plasma membrane resorption bafilomycin incisors effect differences ```

Inhibition of H-ATPase proton pump in stomach reduces ____ • ____ can contribute to tooth decay, so blocking HATPase in stomach can help oral health.

acidity | acid reflux

Secondary active transport Doesn’t require binding of ____ Utilizes gradient of another particle (e.g., ____) to provide energy Gradient ultimately established by ____ Direction of exchange can be the same (____) or opposite (____) Binding of Na+ triggers ____ changes in protein • Na+ is the energy source in nearly all active transport ◦ Cxn within the cell is very ____ • Na+ is going along gradient, but it can bring other molecules along for the ride • Mechanism: ◦ Upon Na+ binds, ____ change resulting in opening of site for ____ • ____ eventually brings the Na+ back out (which is why we use so much energy)

``` ATP Na+ ATP symport antiport allosteric ``` low allosteric glucose NaKATPase

Na/amino acid sympor * Coupling energy of Na+ movement to concentrate ____ * If 2 Na+ translocated each cycle, greater ____, can concentrate AAs at higher concentration

amino acids | driving force

Symport and Antiport ``` • Use gradient established by pumps • Let ions like Na+ run down ____ • Couple this energy to that needed to move another ____ in – ____: same direction, or – ____: opposite direction • Degree to which ion can ``` be accumulated across membrane determined by ____ of driving ion and ____.

``` gradient ion symport antiport gradient charges ```

Na+/H+ Antiporter * In most cells to keep proton levels below gradient * Important in ____ cells in adaption to ____ taste (right), kidney, ____, lungs etc. * Coupled with the ____... * Na+ enters, while the H+ ____... * Located closely to the NaKATPase...

taste bud sour gut NAKATPase exits

Active or passive transport? It’s all about the gradients Intestinal epithelium: [glucose] ____ in than out 1. Na+ gradient established using ____ active transport – ATP hydrolysis powers ____ pump 2. Use energy of Na+ to get ____ into the cell using secondary active transport 3. Let glucose flow out down the ____ through carrier using ____ diffusion

``` higher active NaK glucose gradient facilitated ```

Most cells and tissues use multiple transporters * Na/H, Cl/HCO3 - regulating ____ * NaKATPase * ____

pH | aquaporin

Transporters in ameloblasts • Why channels needed to make enamel? Slc26al, Slc26a6 or Slc26a7 = Sat1, Pat1, and Sut2 respectively, all exhibit chloride, bicarbonate exchanger activities. Mutations lead to multiple disorders induced by the disruption of ion homeostasis. Enamel maturation involves ____ regulation mediated by multiple ion transport/ exchange activities across plasma and endosome membranes Here, the ameloblasts are making enamel Why are there channels that make enamel? • as you move out some of these ____, ____, ____ transporters here, you can see changes in the enamel rods are arranged • It seems counter intuitive that transporting HCO3 can affect the enamel • The ____ dependent changes that these biochemical structures go through are critical in development • Why channels in lysosomes? The lysosomes are very ____, so they are important

``` pH Na HCO3 H pH acidic ```

Osmosis • ____ of diffusion • Forces based on ____ motion that want to make levels of water the same among compartments If membrane permeable to water and impermeable to solute, ____ will move to equal concentration. ____ - Pressure needed to stop water movement

inversion Brownian water osmotic pressure

Cell in isotonic solution Isotonic – no net ____

movement

Cell in HYPERtonic solution Hypertonic solution outside, water ____ cell to equalize concentrations Cell ____

leaves | shrinks

Cell in HYPOtonic solution Hypotonic solution outside, water moves ____ cell to equalize concentrations Cell ____

into | swells

Effects of osmolarity Red blood cell exposed to range of osmolarities Water moves to ____ solute concentrations HypOtonic solution makes the cell an “O”

equalize

What is the osmotic pressure of physiologic saline? • In physiologic saline (____ mM NaCl), red blood cells retain the size/shape they normally have in plasma. • This NaCl concentration is called ____. π = RTφic ``` RT = R is the ideal gas constant, T is the absolute temperature; RT = 22.4 atm φ=phi = osmotic coefficient = 0.93 because Na+ & Cl- don’t completely separate i= number of ions formed by dissociation of solute = 2 because Na + Cl C = molar concentration of solute = 154 mOsm ```

154 | isotonic

Aquaporins Water crosses membranes through ____, or water channels * ____ diffusion for water * ____ is the driving force

aquaporins facilitated osmotic pressure

Aquaporins Different types of aquaporins - vary in their ____, distribution and ____ • Knocking out just the aquaporin transporter isn't necessarily ____... usually have backups...

regulation roles fatal

Water crosses membrane through aquaporins * Permeability of membrane to water much ____ than predicted by its ____ permeability * Water passes through membrane through ____ * Amino acids of proteins ____ when facing lipids, ____ in canal – provides ____ stability

``` higher lipid aquaporins non-polar polar energetic ```

Water crosses membrane through aquaporins • Defective distribution of ____ in salivary gland of Sjögren's syndrome with reduced ____ secretion Why doesn't your mouth swell when you drink a glass of water? • Why don't your teeth fall out when you eat a salty pretzel?

AQP5 | saliva

Transport Summary • ____ molecules diffuse across membrane – rate based on concentration ____, size etc • ____ molecules use protein transporters to cross • In facilitated diffusion, solutes flow ____ • In primary and secondary active transport an ____ input is required • Osmotic pressure created by limited permeability of ____ • Coincident presence of multiple ____ necessary for cell function

``` uncharged/small gradient charged/larger downhill energy solutes transporters ```