M&R S2 - Membrane Permeability and Cell Volume/pH Regulation Flashcards Preview

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Flashcards in M&R S2 - Membrane Permeability and Cell Volume/pH Regulation Deck (51):
1

What properties of solutes determines whether they can pass through a phospholipid bilayer?

Hydrophobic
Small
Uncharged Polar

2

What types of solutes can't pass through a phospholipid membrane?

Large, charged, or polar molecules cannot make it through a membrane

Ions can also not pass through a membrane

3

What is passive diffusion?

What determines rate of PD?

Diffusion that is dependent on:

Permeability
Concentration gradient

Rate increases linearly with increasing concentration gradient

4

What is a permeability coefficient?

What is the permeability coefficient of water?

A numerical expression of permeability of a solute

Expressed in cm/s

5x10-3 cm/s

5

What could be said about the permeability of hydrophobic vs hydrophilic solutes in terms of permeability coefficient?

Hydrophobic molecules have a higher PC

Hydrophilic molecules smaller (tend to be

6

What is the key function of a phospholipid bilayer in terms of their interaction with hydrophilic molecules?

Act as a permeability barrier to hydrophilic molecules

7

How is the movement of hydrophilic molecules across a membrane mediated and regulated?

What roles do these processes have?

By specific membrane transport systems

Transport processes are important in:

Maintenance of intracellular pH, ionic composition, metabolic fuels and volume

Extrusion of metabolic waste and toxins

Generation of ion gradients

8

What is facilitated diffusion?

Name two models of facilitated diffusion

Permeability of a membrane to a substance is 'facilitated' by specific proteins in the bilayer

Models include Carrier molecules (ping pong) and channel proteins

9

Why is facilitated diffusion a saturable process?

Limited number of proteins in the membrane means a maximum rate can be achieved when all transporters are busy

10

What effect does facilitated diffusion have on equilibrium points of solutes moving across the membrane?

Has no effect, similar to enzymes

11

What is channel protein gating?

Some channel proteins may be gated, meaning that they open or close in response to stimulus such as:

Ligand binding
Voltage change
ATP binding

12

What is active transport?

Active transport allows transport of ions or molecules against unfavourable electrical or chemical gradients requiring energy from the hydrolysis of ATP

13

What determines whether a solute must be transported by active transport?

The free energy change of the transported species

This is in turn determined by:

Concentration gradient

Electrical potential across the membrane bilayer (only when the molecule is charged)

14

What percentage of cellular energy can be expended on active transport?

Some cells spend 30-50% of ATP on AT

15

What are co-transporters?

Hint: Secondary active transport

Membrane proteins that will transport more than one ion or molecule per reaction cycle

In this way the transport of one substance can be linked to the concentration of another (secondary active transport)

16

What are the three types of membrane transport?

Uniport - One molecule/ion transported, one direction

Symport - Two molecules/ions, one direction

Antiport - Two molecule/ions, opposing directions

17

Give an example of Symport SYSTEM found in the small intestine and kidney

Na+/Glucose co-transport system

Entry of Na+ provides energy for the entry of glucose against the concentration gradient

18

What is Na+/K+ - ATPase and how does it work?

Hint: Form AND function

What it is:

A plasma membrane associated pump with 2 subunits, Alpha and Beta

Alpha - Contains binding sites for Oubain, K+ extracellularly and Na+ and ATP intracellualrly

Beta - Gycoprotein, Oligosaccharide chains direct pump to the surface

Called a P-type ATPase
(ATP phosphorylated Asp, producing phosphoenzyme intermediate)

What it does:

Uses ATP to transport 2K+ into the cell and 3Na+ out (Active transport/Antiport)



19

How much of the BMR is used by the Na+/K+ ATPase proteins in a cell?

25% of BMR

20

How is Na+/K+ ATPase controlled?

Oubain binding inhibits transport

21

What processes is Na+/K+ ATPase involved in?

Forms Na+ and K+ gradients necessary for electrical excitability

Drives secondary active transport processes such as:

Control of pH
Regulation of Cell volume
Regulation of Ca2+ concentration
Absorption of Na+ in epithelia
Nutrient uptake (Eg. Glucose in small intestine)

22

What is the relevance of the interaction of K+ channels and Na+/K+ ATPase?

K+ diffusion down the concentration gradient set up by the Na+/K+ ATPase through K+ channels is mainly responsible for membrane potential

23

What is the importance of intracellular Ca2+ concentration control?

High Ca2+ concentration is toxic to cells

24

What is the concentration difference in intra and extra cellular Ca2+ concentration?

The is a `20,000 fold difference in intra and extracellular concentration

Intra -

25

What is the function of Ca2+ ATPases?

Control of resting Ca2+ concentration intracellularly

Uses ATP to pump ions

26

What are the two major forms of Ca2+ ATPases?

Where are they found?

SERCA and PMCA

a.k.a.
Plasma membrane Calcium ATPase
Sarco(endo)plasmic reticulum calcium ATPase

Names denote where they're found

27

Describe the action of PMCA

Removes residual Ca2+ from the cell in exchange for H+

Uses ATP (Active transport/Antiport)

High affinity, Low capacity

28

Describe the action of SERCA

Accumulated Ca2+ in the SR/ER in exchange for H+

Uses ATP (Active transport/Antiport)

High affinity, low capacity

29

What is mitochondrial Ca2+ uniport?

A uniporter that operates at high Ca2+ concentration to move Ca2+ into the mitochondria and help prevent cell damage

30

Outline the normal function of the Na+/Ca2+ Exchanger (NCX)

Utilises secondary active transport

Expels 1 Ca2+ in exchange for 3Na+

To do this it uses the Na+ concentration gradient set up by the Na+/K+ ATPase

Electrogenic - Current flows in direction of Na+ gradient

Activity is membrane potential dependent

Antiport

Low affinity, high capacity

Removes MOST Ca2+ - Expels intracellular Ca2+ during cell recovery (after an action potential)


31

Outline how NCX function changes in Ischaemic conditions

ATP depleted, Na+/K+ ATPase inhibited

Na+ builds up in the cell, causing depolarisation

NCX reverses (Sodium out, Calcium in) in an effort to repolarise the cell

32

When cellular buffering capacity is exceeded, how is pH controlled/returned to the set point?

Membrane transporters

Acidification opposed by expelling H+ or inward movement of Bicarbonate (activation of NHE and NBC)

Alkalisation opposed by expelling bicarbonate (activation of AE)

33

What membrane transporters are involved in acid extrusion?

Na+/H+ exchanger (NHE)

Na+/Cl-/HCO3-/H+ co-transporter (NBC)

Both raise intracellular pH

34

Describe the function of the Na+/H+ Exchanger (NHE)

Hint: Include inhibitors/activators

Moves 1Na+ in, 1H+ out, therefore electroneutral

Uses Na+ Concentration gradient set up by the Na+/K+ ATPase to achieve this

Raises pH intracellularly

Helps regulate cell volume

Activated by growth factors
Inhibited by amiloride

35

Outline the function of the Na+/Cl-/HCO3-/H+ co-transporter (NBC)

Na+ and HCO3- in (base in)
H+ and Cl- out (acid out)

Uses Na+ concentration gradient set up by the Na+/K+ ATPase

Process can be looked at as coupled Na+/H+ and anion exchange performed by the same exchanger

Raises intracellular pH

Involved in cell volume regulation

36

What is the major cellular base extruder?

Describe its function

Cl-/HCO3- Exchanger (Anion exchanger/AE)

Cl- in
HCO3- out (base out)

Acidifies cell

Involved in cell volume regulation

37

How is cell volume regulated?

Osmotically active ions (E.g. Na+, K+, Cl-) or organic osmolytes (amino acids) are transported in or out of a cell and water follows via osmosis causing cell shrinking or swelling

There is no standard regulation method, different cells use different combination of transporters to achieve regulation

If cell is shrinking:

Influx ions (E.g. Na+ or Ca2+ channels) and osmolytes

If cell is swelling:

Extrude ions (E.g. K+ or Cl- channels) and osmolytes

38

Outline how bicarbonate is reabsorbed from the kidney's proximal tubule

Na+/K+ ATPase removes Na+ from proximal tubule epithelia

NHE can therefore pump Na+ from the lumen into the cell along the concentration gradient in exchange for H+

H+ goes into the lumen and 'picks up' HCO3- to bring it back into the cell

39

What is the main reason for bicarbonate reabsorption from the proximal tubule?

To retain base for pH buffers

40

What is the main goal of renal anti-hypertensive therapy?

Reduce the re-uptake of Na+ and other molecules so less water is absorbed via osmosis

With less water absorbed, blood volume, and therefore blood pressure falls

41

What is the function of Aquaporins?

Describe their involvement in regulation of water reabsorption form the kidney tubules

Allows water to more easily cross the membrane

It's inclusion in the membrane of Kidney epithelia is stimulated by Anti-Diuretic Hormone (ADH) causing increased water re-absorption.

42

What are Loop Diuretics?

Block Na+ re-uptake in the thick ascending Limb of the Loop of Henle

43

What type of drug is amiloride?

How does amiloride affect Na+ re-uptake in the kidney?

Is a potassium sparing diuretic

Acts on both distal (ENaC - Epithelial Na+ Channel) and proximal (NHE) tubules to prevent Na+ re-uptake

44

What is the result of excess aldosterone and how is this treated?

Aldosterone upregulates ENaC and NHE in the kidney tubules to increase Na+ re-uptake

In excess, this can be a contributing factor to hypertension

Spironolactone (Glucocorticoid receptor agonist) is used to treat

45

How is glucose moved from the lumen to the blood by intestinal lumen and kidney tubule epithelium?

SGLUT-1 is a sodium and glucose symporter that moves them into the epithelia from the lumen via facilitated diffusion

Na+/K+ ATPase produces the Na+ gradient that allows co-transport of glucose as Na+ moves down its concentration gradient in SGLUT-1

GLUT transporters move glucose from the cell into the bloodstream

46

What are GLUT transporters?

Transporters that move glucose into the cell

47

What are the different types of GLUT transporters and where are they found?

By what method do these transporters move glucose into cells?

GLUT 1+3:
- Found throughout the body
- Facilitated diffusion (uniport)

GLUT 2:
- Hepatocytes and pancreatic beta cells
- Facilitated diffusion (uniport)

GLUT 4:
- Striated muscle and adipose
- Facilitated diffusion (uniport), Insulin stimulates

SGLUT-1
- Intestine and kidney
- Secondary active transport (symport)

48

What is the main function of GLUT 1 and 3?

Maintain a basal glucose level in cells

49

How does insulin promote glucose uptake into cells?

Up-regulates expression of GLUT4, resulting in more GLUT4 receptors on the cell surface (from storage vesicles)

50

How does the cell prevent glucose efflux when blood concentration of glucose falls to resting levels following a meal?

Glucose is rapidly metabolised to G-6-P upon entering the cell, so intracellular glucose concentration never rises higher than blood glucose concentration

51

What other metabolites use the sodium gradient for their uptake into cells?

Amino acids