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Biomembranes > Transporters and Channels > Flashcards

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
Q

Osmolarity is …

A
  • proportional to concentration of dissolved solutes
  • inversely proportional to osmotic potential
26
Q

Osmotic potential

A

zero for pure water, increasing negative as solute concentration increases

27
Q

How drugs move across the plasma membrane

A

For many drugs the non-ionised form can permeate the membrane

28
Q

Acid ionisation reaction

A

AH <-> A- + H+

29
Q

Base ionised reaction

A

BH+ <-> B + H+

30
Q

Asprin (pKa = 3.5) crossing the GI tract membrane

A

negatively charged asprin diffuses across the membrane of the gastric mucosa and is trapped in the plasma -> good absorption

31
Q

How can the proportion of drug ionisation be determined

A
  • 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

Biomembranes (12 decks)

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