Transporters

Question 1

What dictates how well a compound crosses a membrane

Answer 1

Lipid solubility
Degree of ionisation
pH differences between compartments

Question 2

2 types of transporter

Answer 2

Facilitative
Secondary active (co-substrate)
- neither use ATP

Question 3

Location of OATPs

Answer 3

Sinusoidal membrane of liver

Question 4

OATPs are encoded by ..

Answer 4

SLCO1-6

Question 5

Substrates for OATPs

Answer 5

Anions with high MW
Statins, rifampicin, benzylpenicillin

Question 6

OAT main role

Answer 6

Renal excretion

Question 7

Location of OATs

Answer 7

1-3 on basolateral membrane of kidney
4 on apical membrane of kidney

Question 8

Substrates for OATs

Answer 8

Sulphate or glucuronide conjugates

Question 9

OCT locations

Answer 9

OCT1 - sinusoidal face of liver
OCT2 - basolateral membrane of kidney

Question 10

OCT substrate

Answer 10

Metformin, cisplatin

Question 11

PEPT locations

Answer 11

PEPT1 - intestine and kidney
PEPT2 - kidney

Question 12

PEPT substrates

Answer 12

Penicillins, ACE inhibitors
(Proton dependent)

Question 13

MATE locations

Answer 13

MATE1 - liver and kidney
MATE2 - kidney only

Question 14

MATE function

Answer 14

Proton dependent transport of cations for biliary and renal excretion

Question 15

Membrane involved in intestine transport

Answer 15

Enter enterocytes through brush boarder membrane then enter hepatic portal vein through basolateral membrane

Question 16

Membrane involved in liver transport

Answer 16

Across sinusoidal membrane to enter

Out across canalicular membrane to bile or sinusoidal membrane to blood

Question 17

Explain diclofenac transport

Answer 17

CYP2C9 and UGT metabolism makes acyl glucuronide
OAT2 and 4 renal excretion

Question 18

2 common polymorphisms

Answer 18

OATP1 - toxic levels of statins in muscle
OCT2 - nephrotoxicity from cisplatin