Transporters and Channels Flashcards

- Identify the criteria for the existence of carrier-mediated transfer - Recognise that gene "families" of transporters have evolved - Recall Michaelis-Menten equation for the kinetics of simple carrier-mediated transport - Understand how Km and Vmax provide descriptions of carrier function - Distinguish between competitive and non-competitive effects on transport of a solute - Appreciate the consequences of coupling of substrate fluxes through a carrier

1
Q

How can we increase solute movement across a membrane or cell layer

A
  • increase area of flux (microvilli, alveoli)
  • decrease x
  • increase rate of cell metabolism
  • increase D (alter bilayer composition or introduce pores)
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2
Q

What is a solute flux

A
  • predicted by passive diffusion
  • down a concentration gradient
  • avoids bilayer
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3
Q

Examples of substrate-specific pores

A
  • e.g. glucose transporter
  • e.g. hexoses, amino acids, lactate
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4
Q

Important characteristics of pores

A
  • solute flux
  • substrate specific
  • saturable
  • specific inhibitors/inactivators (antagonists)
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5
Q

What is the transportome

A
  • Human Genome Organisation recognises 1289 genes as transporters and channels
  • 406 ion channels
  • 863 transporters
  • classified into structurally related super-families and families
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6
Q

Importance of transporters in gut

A
  • vital to absorption of micro and macro nutrients, and also drug absorption
  • digestion
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7
Q

Principle sites of carrier-mediated drug transport

A
  • blood-brain barrier
  • GI tract
  • placenta
  • renal tubule
  • biliary tract
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8
Q

Why is carrier-mediated transport important

A
  • can transport drugs that are chemically related to endogenous substances such as neurotransmitters
  • e.g. dopamine is transported through blood-brain barrier by transporters
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9
Q

Ohms Law

A

I = V/R (current or charge flow)

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10
Q

Poiseuille equation

A

blood flow = change in P/Peripheral resistance (blood flow)

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11
Q

Define Kp

A

lipid-water partition coefficient
= change in cm / change in c

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12
Q

Kp for a hydrophobic molecule

A

Kp > 1

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13
Q

Kp for hydrophilic molecule

A

Kp < 1

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14
Q

What is ‘R’

A

Gas constant (8.3 J/K.mol)

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15
Q

What is ‘T’

A

Absolute temperature (K)

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16
Q

What is ‘n’

A

Viscosity of barrier

17
Q

What is ‘r’

A

Radius of diffusing molecule (related to molecular weight)

18
Q

Stokes’ Law

A

a perfect sphere travelling through a viscous liquid feels a drag force proportional to the frictional coefficient

19
Q

Rate of solute diffusion (J) is proportional to

A
  • permeability of coefficient P
  • surface area A of membrane
  • concentration difference (change in c)
20
Q

How frictional effects predict passive permeability

A
  • molecular size -> small, increase P; large, decrease P
  • molecular shape - straight, increase P; globular, decrease P
  • membrane viscosity - short R chains, -C=C-, inc. T0, increase P
21
Q

How lipid solubility predicts passive permeability

A
  • Kp high (e.g. O2, CO2, anaesthetics, lipophilic group), increase P
  • Kp low (e.g. sugars, amino acids, ions, polar charged groups) decrease P
22
Q

How unstirred layers predict passive permeability

A

increases overall “thickness” of barrier

23
Q

How charge effects predict passive permeability

A
  • molecular charge affects Kp
  • hydrogen-bonding alters effective molecular size / shape, Kp
24
Q

What is osmosis

A

(net solvent flow) water moving from region of higher to lower water potential, showing bulk flow

25
Osmolarity is ...
- proportional to concentration of dissolved solutes - inversely proportional to osmotic potential
26
Osmotic potential
zero for pure water, increasing negative as solute concentration increases
27
How drugs move across the plasma membrane
For many drugs the non-ionised form can permeate the membrane
28
Acid ionisation reaction
AH <-> A- + H+
29
Base ionised reaction
BH+ <-> B + H+
30
Asprin (pKa = 3.5) crossing the GI tract membrane
negatively charged asprin diffuses across the membrane of the gastric mucosa and is trapped in the plasma -> good absorption
31
How can the proportion of drug ionisation be determined
- the proportion of ionisation of a drug depends upon both the pKa of the drug and the local pH - the pKa = pH at which 50% of drug is ionised and 50% is un-ionised