Lecture 6

Question 1

Transport system

Answer 1

moving molecules across cell membrane – mats from surrounding is needed for energy and biosynthesis, cells need to export metabolic waste and toxins

Question 2

Stages for transporters

Answer 2

1. bind cargo molecule on one side of membrane
2. change in protein structure
3. release on opposite site

Question 3

disease relavance of transporterers

Answer 3

determinants in pharmacokinetic, safety, efficacy of drugs
transporters work w/ enzymes in drug absorption and elimination
drug substitute translocated across membrane. drug inhibitor impair uptake/efflux of another drug
ATP-dependent transporters (ATP binding cassette, ABC) and solute carriers (SLC) are important in drug distribution
ABC transporter: P-glycoprotein is a multidrug resitance and exports many drugs

Question 4

First class transporters

Answer 4

uses gradient to transport from high concentration to low concentration
requires no chemical energy input
Uniports, antiports, symports

Question 5

First class transporters examples

Answer 5

Na/Glucose: reaborbs glucose into kidneys to treat T2 diabetes. Transports high Na outside cell into cell bringing glucose into cell which is symport Na gradient
SERT: transports serotonin from synaptic cleft back to neurons to terminate serotonin. target for many drugs against depression and anxiety. Depends on Na + Cl for conformation change. Uses Na+ gradient
ATPase: 1st class transporter that generates gradient

Question 6

Second class transporter

Answer 6

primary active transporter that transports solutes against concentration gradient
ATP hydrolysis provides energy for this transporter
Na+/K+ exchanging ATPase: uses ATP to drive translocation of Na & K (antiport) to maintain low Na and high K in mammal cells

Question 7

ATP-binding Cassette (ABC) transporter

Answer 7

second class transporter
Uses ATP hydrolysis for energy, prokary have lots of ABCs for import and export
Eukary mainly have ABCs for export
Structure: transmembrane domain where substrate binds for conformational change occurs, 2 TMDs + 2 NBS (nucleotide binding domain), ATP cassette where ATP binds
function: drug resistance, extrude xenobiotics

Question 8

ABC exporters PgP

Answer 8

alternating access for multidrug transporters
hydrolysis of ATP drives NBS apart and back to stage 1