Membrane Transport 14

Question 1

Membrane Permeability

Answer 1

• membranes allow compartmentalization
• lipid bilayers are permeable to some non-polar substances but not polar molecules, which requires protein-mediated transport
• spontaneous passive transport must be down a concentration gradient
• oxygen, CO2, N2, steroids, hormones can diffuse across

Question 2

Protein mediated transport

Answer 2

• may be facilitated by pores or channels
• non-stoichiometric
• no conformational changes
• passive
• Selective
• May be gated by ligand or voltage
• or by transporters
• stoichiometric
• conformational changes
• passive or active
• specific
• may be regulated

Question 3

Transport proteins

Answer 3

• can bind more than one type of ligand
• undergo conformational changes during the transport process
  
  • uniport: moves one substance at a time
  • symport: transports 2 different substances in same direction
  • antiport: moves 2 different substances in different directions

Question 4

Uniport of Glucose

Answer 4

• Glucose transporters (GLUT) undergo conformational changes during transport process
• allow glucose to pass through a membrane down a conc gradient

Question 5

Na, K-ATPase changes conformation as it pumps ions across the membrane (antiport)

Answer 5

1. 3 intracellular Na+ ions binds
2. ATP binds
3. A phosphoryl group is transferred from ATP to an Asp side chain of the pump. ADP released
4. The protein conformation changes, exposing the Na+ binding site to the cell exterior. Na+ ions dissociate
5. 2 extracellular K+ ions bind
6. The aspartyl phosphate group is hydrolyzed. Pi is released
7. The proteins conformation changes, exposing the K+ binding sites to the cell interior. The K+ dissociates

Question 6

Effect of Na,K-ATPase on cellular ion conc

Answer 6

• mammalian cells maintain ion gradients across the plasma membrane: the large Na+/K+ gradient is maintained by Na,K-ATPase pump which used 1/3 of our total energy at rest
• conc gradient favours movement of Na+ to inside, and K+ to outside

Question 7

Glucose transport in an intestinal epithelial cell

Answer 7

• following a meal, glucose is taken up by IECs and transported to the bloodstream where it is tightly regulated
• Glucose uptake from the guy to a higher concentration in the ICE is coupled to Na+ uptake (symport)
• GLUT transporters move glucose from IECs to the blood by passive diffuction and also into peripheral cells by the same manner (uniport)
• ATP is hydrolyzed to maintain the Na+/K+ gradient across the plasma membrane (antiport: active transport)

Question 8

Protein traffic roadmap

Answer 8

• protein destinations are established by embedded targeting sequences
• cystol: no targeting sequence (default)
• nucleus: internal basic sequence
• mitochondria: N-term amphipathic helix
• peroxisomes: C-terminal SKL sequence
• ER: N-terminal hydrophobic signal sequence. Become embedded in membrane with transmembrane helices
• retention in ER: C-terminal KDEL sequence
• lysosomes: attachment of mannose-6-PO4

Question 9

Protein translocation into ER

Answer 9

• proteins destined for secretion synthesized with N-terminal signal peptide
• depending on presence of one or more TM domains, proteins are lumenal/secreted, or embedded in a membrane

Question 10

Vesicular transport

Answer 10

• vesicles bud from donor membrane and fuse with target membranes (eg. ER -> Golgi -> Plasma membrane)
• proteins are targeted or retained depending on embedded signals
• most lipids are synthesized in smooth ER, thus bulk flow is directed to other membranes

Question 11

Mechanisms of membrane fusion

Answer 11

• fusion of lipid bilayer cannot be random: it depends on correct addressing (specific vesicle to correct membrane) plus physical disruption of reformation of the bilayer leaflets
• is facilitated by SNARE proteins which adopt a 4-helix bundle to drive close contact of opposing membranes encouraging membrane fusion