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
How can we increase solute movement across a membrane or cell layer
- increase area of flux (microvilli, alveoli)
- decrease x
- increase rate of cell metabolism
- increase D (alter bilayer composition or introduce pores)
What is a solute flux
- predicted by passive diffusion
- down a concentration gradient
- avoids bilayer
Examples of substrate-specific pores
- e.g. glucose transporter
- e.g. hexoses, amino acids, lactate
Important characteristics of pores
- solute flux
- substrate specific
- saturable
- specific inhibitors/inactivators (antagonists)
What is the transportome
- Human Genome Organisation recognises 1289 genes as transporters and channels
- 406 ion channels
- 863 transporters
- classified into structurally related super-families and families
Importance of transporters in gut
- vital to absorption of micro and macro nutrients, and also drug absorption
- digestion
Principle sites of carrier-mediated drug transport
- blood-brain barrier
- GI tract
- placenta
- renal tubule
- biliary tract
Why is carrier-mediated transport important
- can transport drugs that are chemically related to endogenous substances such as neurotransmitters
- e.g. dopamine is transported through blood-brain barrier by transporters
Ohms Law
I = V/R (current or charge flow)
Poiseuille equation
blood flow = change in P/Peripheral resistance (blood flow)
Define Kp
lipid-water partition coefficient
= change in cm / change in c
Kp for a hydrophobic molecule
Kp > 1
Kp for hydrophilic molecule
Kp < 1
What is ‘R’
Gas constant (8.3 J/K.mol)
What is ‘T’
Absolute temperature (K)
What is ‘n’
Viscosity of barrier
What is ‘r’
Radius of diffusing molecule (related to molecular weight)
Stokes’ Law
a perfect sphere travelling through a viscous liquid feels a drag force proportional to the frictional coefficient
Rate of solute diffusion (J) is proportional to
- permeability of coefficient P
- surface area A of membrane
- concentration difference (change in c)
How frictional effects predict passive permeability
- 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
How lipid solubility predicts passive permeability
- Kp high (e.g. O2, CO2, anaesthetics, lipophilic group), increase P
- Kp low (e.g. sugars, amino acids, ions, polar charged groups) decrease P
How unstirred layers predict passive permeability
increases overall “thickness” of barrier
How charge effects predict passive permeability
- molecular charge affects Kp
- hydrogen-bonding alters effective molecular size / shape, Kp
What is osmosis
(net solvent flow) water moving from region of higher to lower water potential, showing bulk flow
