transporters

Question 1

what are the three major families of transporters

Answer 1

1. SLC (solute carrier family)
2. P-type ATPases
3. ABC transporters

Question 2

what are characteristics of P-type ATPases

Answer 2

10 TM proteins
hydrolyse ATP on cytoplasmic face
mostly move inorganic ions
ex: Ca ATPases ubiquitous (PMCA, effluxes calcium to return to baseline IC [Ca])
H/K atp ases only in gastric parietal cells

Question 3

what are some examples of p-type ATPases exploited therapeutically

Answer 3

Na/K atpases allow repolarisation of plasma membrane after AP. 3 sodium out 2 potassium in.
anti arrythmic drugs like digoxin target this transporter. reduced exciatability.

H/K atpases secrete protons from parietal cells in stomach.
anti ulcer drugs like PPI omeprazole target this transporter.

Question 4

what are characteristics of SLC transporters

Answer 4

ubiquitous membrane proteins on cell surfaces and organelles.
utilise ion gradients to facilitate transport

Question 5

what functions do SLC transporters carry out

Answer 5

metabolic functions (transporters amino acids, fatty acids, peptides, sugars, bile acids, urea, vitamins)

signalling functions (AA NT like glutamate glycine and GABA and amines like NA adrenaline 5HT dopamine and ACh)

ion movements (cu, zn, Fe, p, S)

Question 6

what are some examples for the therapeutic manipulation of SLC transporters

Answer 6

SERT is target of SSRIS. transports 5HT in CL- dependent way.

thiazide diuretics target Na-Cl symporters SLC12A3
loop diuretics target NA-K-Cl symporters SLC12A1 ex: furosemide

SLC5A2 mediates 90% of glucose re absorption in kidney
inhibition: glucosuria and reduced plasma glucose. used in DM2
ex: dapagliflozin

Question 7

what are the characteristics of ATP Binding cassette transporters

Answer 7

12 TM proteins
2 subunits each have 6TM domains and nucleotide binding domains where ATP binds
found on cell surfaces and organelles.
ATP in cytoplasm is used to facilitate solute transport.

Question 8

what are some substrates of ABC transporters

Answer 8

metabolic: cholesterol
signalling: prostaglandins and leukotrienes
ion: cl- hco3-

Question 9

what are examples of therapeutic manipulation of ABC transporters

Answer 9

expression increases of ABCB1 ABCB4 ABCC1 ABCC2 in conditions promote resistance to chemotherapy and antibacterial
efflux drugs like cetirizine and loperamide

ABC transporters C9&8 combine with Kir channels to generate KATP channels. high glucose conc. increases ATP in pancreatic B cells this causes depolarization (channel closed less pot efflux) leading to insulin release.
low glucose conc. increases ADP opening Kir channels leading to hyperpol. insulin release switched off.
inhibitors like glibenclamide used in DM2