Control of pH (flipped)

Question 1

Why is it important to control intracellular pH?

Answer 1

Small change in PH value means large change in number of protons due to logarithmic scale

(A 0.3 change in PH means a doubling or halving in proton concentration)

Question 2

How can proteins change due to pH? (3)

Answer 2

-Charge in protein changed
-Change in protein conformation
-Change in function

Question 3

What does cell have to regulate intracellular pH? (2)

Answer 3

1. Acid Extruders – Like the furnace - removing H+ from or adding HCO3- to a cell.
   Rate of acid extrusion - JE
2. Acid Loaders – Like an air conditioner – removing HCO3- from a cell.
   Rate of Acid Loading - JL

Question 4

How do Acid Extruders and Acid loaders affect each other?

Answer 4

These two processes balance out, no net movement of protons across membrane
So steady PH rate

Question 5

What exchanger used for Acid extrusion?
and Acid loading?

Answer 5

Acid Extrusion - Sodium-proton exchanger (Na+/H+)
Acid Loading - Chloride-bicarbonate exchanger (HCO3-/Cl-)

Question 6

What does a pH buffer do?

Answer 6

The buffering systems act to minimise pH changes and help protect the cell from damage
(can’t stop pH changes or reverse them)

Question 7

What is buffering power?

Answer 7

The amount of strong base that must be added to a solution in order to raise the pH by a given amount

Question 8

What does buffering by proteins rely on? (2)

Answer 8

Relies on the ability of COOH and NH2 groups on amino acids to donate or receive protons

if pH increased COOH releases H+
if pH decreased NH2 receives H+

Question 9

What does the Na+/H+ (Acid Extrusion) rely on?

Answer 9

Inward Na gradient created by the Na/K pump (ATPase)

Question 10

What does NHE and AE stand for? (2)

Answer 10

-Na+/H+ Exchanger
-Anion exchanger (HCO3-/Cl- exchanger)

Question 11

What is allosteric modification in NHE?

Answer 11

Protons other than the one being transported bind to the NHE protein, leading to conformational change which increases the activity of the protein
(NHE has proton bonding site)
Makes rate of acid extrusion non-linear

Question 12

What is set pint of NHE?

Answer 12

like an on/off switch – when pH is more alkaline than the setpoint the exchanger is inactive

Question 13

How does pH affect NHE?

Answer 13

Rate of activity increases with lower PH

Question 14

What is the role of NHE1 and where is it found?

Answer 14

-Housekeeping function – primary roles in regulation of pHi and control of cell volume

-Found in basolateral membrane of epithelial cells (others such as NHE3 found on apical membrane)

Question 15

What is NHE1 inhibited by?
What concentration is needed?

Answer 15

-Inhibited by ‘low’ concentrations of amiloride and its analogue EIPA

-Sodium protein exchanger (NHE) – Roughly 1 millimolar for full inhibition, lower amiloride needed for inhibition

Question 15

What is concentration of amiloride is needed to inhibit ENAC (amiloride sensitive sodium channel)?

Answer 15

50 millimolar

Question 16

How does HCO3- removal cause acidification?

Answer 16

Removing HCO3- from cell leaves H+ behind
-> acidification

Question 17

How does pH affect AE (Cl-/HCO3- exchange) ?

Answer 17

Low activity at acidic PHs and increases activity when alkaline

Question 18

How many subtypes are there in the AE family?

Answer 18

4

Question 19

Describe how AE (Cl-/HCO3- exchangers) which fold work in terms of structure? (2)
And how do these differ to regular AEs?

Answer 19

-14 transmembrane spans, protein has two spans and fold over each other, transmembrane span 10 and 3 come together which forms binding clef for ion
(either Cl- or HCO3-)

-Protein goes through conformational change as ions bind

-Sodium dependent Cl- HCO3- exchangers are a separate type to these AE Cl- HCO3- exchanger which are independent of NA+

Question 20

How is AE1 used in the kidney?

Answer 20

Chloride/Hamburger shift is process body uses to carry CO2 in blood in form of bicarbonate