Deck 5: Absorption and Transport of Toxicants Through Membranes: Toxic Damage to Membranes

Question 1

What are aquaporins and how does toxicity result from disrupting their actions?

Answer 1

Aquaporins (APQ) are proteins that allow water to move rapidly across lipid membranes. Lithium, a medication for bipolar disorder, causes major increases in urine production due to interference in the expression of APQ2 mRNA and the 3Na⁺,2K⁺-ATPase in the kidney.

Question 2

Using the Henderson-Hasselbalch equation, figure if someone accidently consumed the same concentration of the weak acid herbicide 2,4- dichlorophenoxyacetic acid, pK_a = 2.8, and the weak base herbicide atrazine, pK_a = 1.7, in the human intestinal pH of 6, which would be more absorbed on this factor alone.

Answer 2

For weak acids pH = pK_a + log [ionized]/ [non-ionized], 6 = 2.8 + log [ionized]/ [non-ionized] 
6 - 2.8 = 3.2 = log [ionized]/ [non-ionized]  10^3.2 = [ionized]/ [non-ionized] = 1585 [ionized]/1 [non-ionized] where non-ionized is favored for absorption - so predicted little absorption.
For weak bases pH = pK_a + log [non-ionized]/ [ionized], 6 = 1.7 + log [non-ionized]/ [ionized] 
6 - 1.7 = 4.3 = log [non-ionized]/ [ionized] 10^4.3 = [non-ionized]/ [ionized] = 199953/1 [non-ionized]/[ionized], so highly favored for absorption of the non-ionized atrazine.

Question 3

Which transporter confers resistance to the cancer chemotherapy agent paclitaxel?

Answer 3

The ABC transporter P-glycoprotein pumps out these agents and confers protection to the cancer cell.

Question 4

How do surfactants increase the permeability of membranes? These are sometimes used in pesticide mixtures to make the mixture miscible with water.

Question 5

What is the Fenton reaction and how does this damage membranes?