Question

Some drugs work by increasing the amount of protons in the intermembrane space of the mitochondria beyond what is normally present under standard conditions. A steeper concentration gradient means it takes more energy to pump protons. Below is a table indicating the concentration of various components in a patient not exposed to the drug. However, you want to predict how these components change when treated with this drug. Next to each component, write “increase”, “decrease”, or “no change” when the mitochondria are treated with the drug.

Metabolite	Normal Patient Levels	Patient exposed to drug
NAD+	75 uM
NADH	50 uM
O2	90 mm Hg
FADH2	10 uM
ATP	100 uM

Answer 1

Metabolite	Normal Patient Levels	Patient exposed to drug
NAD+	75 uM	decrease
NADH	50 uM	increase
O2	90 mm Hg	no change
FADH2	10 uM	increase
ATP	100 uM	increase

High proton concentration in double membrane space creates high gradient so proton acceptor or electron donor for NADH will take more energy i.e. reaction will be slow thus accumulating the NADH in the mitochondria thus NAD+ concentration will be decreased. O2 will not be consumed and is in equilibrium with lungs gas exchange so will not change. Like NADH, FADH2 will also have same fate. Increased H+ concentration in double membrane space will automatically increase the ATP generation by transporting H+ ion from membrane space to cytoplasm