Lecture 18 Membrane Transport 1

Question 1

What are the majority of transport proteins?

Answer 1

Most are polytopic, transmembrane integral membrane proteins

Question 2

What is the plasma membrane permeable to?

Answer 2

Lipophilic molecules

e.g. steroid hormones

Question 3

What is the plasma membrane impermeable to?

Answer 3

Hydrophilic/Polar molecules

Question 4

What is the function of membrane proteins?

Answer 4

Facilitate the transport of specific molecules across the membrane

Question 5

Since hydrophilic/polar molecules are impermeable, how do they pass the membrane?

Answer 5

They need specific transport mechanisms

Question 6

What determines the ionic composition of the cell?

Answer 6

The activity and protein levels of specific transporters

Question 7

What governs the biochemical/metabolic characteristics of a cell?

Answer 7

The expression of specific transporters

Question 8

What might be one way of regulating metabolism?

Answer 8

Alteration in expression levels of transporters

Question 9

Passive Transport

Answer 9

Molecules move down a concentration gradient by using energy stored in the gradient
e.g., ion channels

Question 10

Active Transport

Answer 10

Molecules move against a gradient by using biochemical energy stored in ATP
e.g., pumps/ATPase

Question 11

What are the two types of energy independent movement of molecules down a gradient?

Answer 11

Simple Diffusion

Facilitated Diffusion

Question 12

Simple Diffusion

Answer 12

Molecules that are small, non-polar and uncharged polar diffuse freely across the membrane via simple diffusion
Unaided

Question 13

Facilitated Diffusion

Answer 13

Molecules that are large and charged are unable to cross the membrane so they need a facilitator (i.e. proteins - function as channels or transporters)

Question 14

When is energy at a minimum?

Answer 14

When concentration across a semi-permeable membrane is equal

Question 15

Equation for Free Energy of an Uncharged Molecule

Answer 15

ΔG = 2.303 RT log(c2/c1)

Question 16

Equation for Free Energy of a Charged Molecule

Answer 16

ΔG = 2.303 RT log(c2/c1) + ZFΔV
Z is the electrical charge of the transported species
F is the Faraday’s constant
Δ V is the membrane potential

Question 17

What does a positive free energy mean in terms of transport?

Answer 17

Active transport

Question 18

What are the two types of ATP utilizing proteins?

Answer 18

P type ATPases

ATP Binding Cassette Transporters

Question 19

List exaples of P Type ATPases

Answer 19

Na+K+-ATPase
Plasma Membrane Ca2+-ATPase (PMCA)
SR Ca2+-ATPase (SERCA)
H+-K+-ATPase

Question 20

Give an example of ATP Binding Cassette Transporters

Answer 20

Multi drug resistance protein

Question 21

Why are P type ATPases considered P type?

Answer 21

Transporter forms a covalent bond with the phosphate (cleaved from ATP) to form an enzyme-phosphate intermediate

Question 22

In P Type ATPases, where does the energy come from?

Answer 22

Uses energy from ATP hydrolysis to drive transport against gradient

Question 23

In P type ATPases, what residue of the transporter is phosphorylated?

Answer 23

Aspartate

Question 24

What are the functions of the Sodium Pump?

Answer 24

Set up Na+ and K+ gradients across PM
Makes neurons and muscle cells electrically excitable, controls cell volume, drives the active transport of sugars and AAs
3 Na+ out, 2 K+ in

Question 25

How much of brain ATP is used by the Na+ pump?

Answer 25

25 to 40%

Question 26

Give an example of a Na pump inhibitor

Answer 26

Plant steroids (digitoxigenin and ouabain) Strong effect on heart Can be used in treatment of cardiotonic steroids

Question 27

How do plant steroids inhibit the Na+ pump?

Answer 27

By inhibiting dephosphorylation of E2P

Question 28

Mechanism of action of Cardiac Glycosides

Answer 28

``` Inhibition of Na+K+-ATPase activity Increase Na+ levels in cell Reduce activity of Na+-Ca2+ antiporter Increase in [Ca2+]i Elevated Ca2+ increases contractile force of cardiac muscle ```

Question 29

Name the two Calcium Pumps

Answer 29

Plasma membrane Ca2+-ATPase (PMCA) | Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)

Question 30

Describe PMCA

Answer 30

10 transmembrane domains Transports Ca from cytosol to extracellular side Uses ATP Stimulated by Ca binding protein calmodulin (CaM)

Question 31

Describe SERCA

Answer 31

10 transmembrane domains Transports Ca from cytosol to ER Uses ATP Plays role in relaxation of contracted muscle

Question 32

Describe ABC Transporters

Answer 32

Human genome has ~150 Have common architecture Multi-drug resistance protein/P glycoprotein Pump wide range of small molecules out of cell Use ATP

Question 33

Describe Mechanism of Action of ABC Transporters

Answer 33

See slide 32

Question 34

Describe Secondary Transporters

Answer 34

Not directly driven by ATP Thermodynamically unfavorable flow of one species of ion against a gradient coupled to a favorable flow of another species down a gradient

Question 35

Three types of Secondary Transporters

Answer 35

Antiporters Symporters Uniporters

Question 36

Lactose Permease

Answer 36

Symporter Uses proton gradient generated by oxidation of fuel molecules to drive lactose and other sugars against concentration gradient