Lecture 3+4

• Transmembrane transport is essential in all organisms to acquire raw materials and release byproducts
• Membrane proteins allow transmembrane transport, without them many important molecules couldn't enter the cell
• Summary of transport types

  • Passive transport
  • Active transport
• Passive transport


  Simple diffusion across a permeable membrane to lower energy
• Passive transport


  • Electrically neutral solute
  • Electrically charged solute
• Electrically charged solute passive transport


  Electrochemical gradient (chemical and electrical gradient [Vm, membrane potential])
• Energy during membrane passage

  • Simple diffusion
  • Transporter/permease: facilitated diffusion (reduces activation energy)
• Types of membrane transport proteins

  • Carriers
  • Channels
• Carriers


  • High specificity
  • Slower
• Channels


  • Less specific
  • Faster
• Facilitated diffusion


  1. Coupled transport

  2. Energy from chemical reaction
• Passive transport: GLUT1


  • Glucose transporter in erythrocytes
  • Implicated in diabetes
  • Facilitated diffusion: 50,000x faster than uncatalyzed
  • Passive transport: [glucose] cannot be higher than surrounding medium
  • Transport process can be described like enzyme reaction
• Passive transport: GLUT1 structure


  • Deng et al Nature (2014)
• Electroneutral co-transport: chloride-bicarbonate exchanger


  • CO2 transporter in erythrocytes
  • Increases transport rate >1Mx
  • 14 TM helices
  • Antiporter: Cl-, HCO3-
• Active transport


  • Requires energy
  • From chemical reaction: primary active transport
  • From coupled transport: secondary active transport
• Ion gradients from primary transport provide the energy for secondary active transport, these ion gradients are essential: ionophores (vancomycin) collapse them and kill cells
• Four classes of ATP-powered transport

  • P-type ATPases
  • F and V-type ATPases
  • ABC (ATP binding cassette) transporters
• 1. type ATPases


  • Cation transporters
  • 70 in human genome
  • Phosphorylated on Asp as part of cycle
  • 8-10 TM helices
• 1. type ATPases


  • Ca2+ ATPase (SERCA pump)
  • Uniporter for Ca2+
  • Na+ K+ ATPase
  • Antiporter: 3 Na+/2 K+
  • Create Vm=50-70 mV
  • 25% energy in human used in this reaction
• F and V-type ATPases

  • Proton transport driven by ATP hydrolysis
  • Fo (TM) component
  • F1 component
  • V-type structurally related (Vo, V1)
  • Acidify intracellular compartments
• ABC (ATP binding cassette) transporters


  • Pump amino acids, peptides, proteins, metal ions, lipids, compounds (drugs)
  • MDR1: multi-drug transporter
  • CFTR: Cl- channel
  • Human: 48 genes
  • E. coli 80 genes
• Secondary transport: lactose permease


  • H+/lactose co-transporter (E. coli)
  • Lactose goes in the cell
  • 12 TM helices
  • Protonatable Glu, Arg side chains
  • Major facilitator superfamily
• Aquaporins


  • Transport water across plasma membrane
  • Changes in osmotic pressure cause cells to shrink (hypertonic)/swell (hypotonic)
  • k = 109 s-1 (fastest enzyme catalase k = 4 x 107 s-1)
  • Do not allow H30+ transport (Arg195 repels cations)
  • Chain of waters is prevented: no proton hopping
• Ion channels


  • Differ from transporters
  • Flux ~ unrestrictive diffusion > transporters
  • Ligand- or voltage gated
  • Open only for ms
  • Cannot be monitored biochemically
  • Instead monitored electrically – patch-clamp (monitoring one-few channels)
• Bacterial K+ channel


  • K+ passes 10,000x more readily than Na+
  • 4 subunits, 2 TM helices each
  • Carbonyls coordinate K+ - replace waters
• Voltage-gated K+ channel


  • TM helix with 4 Arg moves according to electric field
• Voltage- and ligand-gated channels in neurons

  1. Muscle contraction

  2. Action potential in the motor neuron opens voltage-gated Ca2+ channel and releases acetylcholine

  3. Acetlylcholine opens nicotinic acetylcholine receptor (ligand-gated channel)

  4. Acetylcholine transient ligand

  5. Na+/K+ antiporter

  6. Associated with learning and memory and disorders (schizophrenia, epilepsy, drug (e.g. nicotine) addiction, Alzheimer's)

  7. Depolarization of membrane leads to opening of voltage-gated Na+ channel and generation of action potential

  8. Ca2+ channels release Ca2+ from sarcoplasmic reticulum

  9. Same family as GABA and Gly receptors (Cl- and HCO3- channels) and serotonin receptor (cation channels)
• Consequences of defective ion channels: Voltage gated Na+ channel - muscle paralysis/stiffness, Cystic fibrosis
• Toxins target ion channels: Fugu tetradotoxin - voltage-gated Na+ channel, Black mamba dendrotoxin - voltage-gated K+ channel, Tubocurarine, conbrotoxin, bungarotoxin - acetylcholine receptor
• Topic 2: Transmembrane transport - Key points

  • Movement of polar compounds across membranes requires transporters
  • Passive diffusion
  • Active transport requires energy
  • Primary active transport
  • Secondary active transport: coupled flow of two solutes
  • Uniporters, symporters, antiporters
  • Ionophores
  • Examples: P-type, F-type, V-type ATPases, ABC transporters, Aquaporins, Ion channels