Question

NATIONAL CENTER FOR CASE STUDY T HINGS SCIENCE Part III - Subcellular Metabolite Analysis Detailed analysis of the damaged cells showed that ATP levels in the mitochondria were very low. Levels of pyruvate and acetyl coenzyme A (COA) were normal. You begin to suspect a malfunction of a specific cellular metabolic pathway and so you request a more detailed analysis of the sub-cellular components of the affected cells from the autopsy. The levels of key metabolites are reported below: Average Metabolite Levels | Metabolite Average Patient Levels Glucose 99 MM Pyruvate 27 PM NAD+ IO AM NADH 400 PM Normal Levels 100 UM 25 PM 75 MM SouM

1. The Mystery of the Seven Deaths--

• The results in Part III suggests which process of respiration [glycolysis, pyruvate processing, citric acid cycle, or the electron transport chain] was affected? Why is this the process you suspect [based on the results]?
• Does cyanide poisoning increase ATP production or decrease it? Explain your answer.

2. The effect of gramicidin--

• List the one(s) that would remain the same.
• List the one(s) that would decrease (or go to zero).
• List the one(s) that would increase.

Answer 1

1. The mystery of the seven deaths;

The cause for the seven deaths is cyanide poisoning. Cyanide is a potent inhibitor of Electron transport chain (ETC). This inhibit the electron transport at cytochrome c oxidase, final electron acceptor of electron transport chain. At this step only during aerobic respiration oxygen is reduced into water by accepting electrons from the substrates from ETC.

# Haemoglobin has higher affinity to cyanide in thousand folds when compared to oxygen. So cyanide takes the place of oxygen and it cannot accept the electron anymore. So the complete ETC is stopped due to the inhibition at final step. This affects the ATP production directly. Less production of ATP is the ultimate cause of death.

2. Effect of gramicidin

Remains same	Decreases (or goes to zero)	Increases
Proton pumping	ATP synthesis	Oxygen uptake (when blocked with oligomycin)
Electron transport	Proton gradient
Oxygen uptake

Gramicidin causes a leaky membrane for proton ions, which lead to the loss of proton gradient formation. So, ATP production will be affected adversely. However, This will not affect the ETC and proton pumping and oxygen uptake. Gramicidin is an uncoupler of oxidative phosphorylation. So, if the oxidative phosphorylation is blocked by oligomycin, gramicidin would increase the rate of oxygen intake.