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An autopsy is performed on a woman who committed suicide. The tests reveal that

ID: 49022 • Letter: A

Question

An autopsy is performed on a woman who committed suicide. The tests reveal that she had high levels of hydrogen cyanide gas in her blood at the time of death. The metabolic poison in hydrogen cyanide gas is cyanide, a toxin which is deadly within minutes of inhalation or ingestion. After doing further testing on the woman, the following information is revealed:

>Blood and tissue oxygen levels are normal

> Blood and tissue glucose levels are normal

> Pyruvate levels are normal

> Cytoplasmic NADH and NAD+ levels are normal

> Cytoplasmic ATP levels are normal

> Acetyl CoA levels are normal

> Mitochondrial NADH and NAD+ levels are normal

> Mitochondrial FADH2 and FADH levels are normal

> Mitochondrial ATP levels are low

Your colleague develops a hypothesis: cyanide inhibits an enzyme in the Krebs cycle. Based on the information given, is your colleague's hypothesis supported or unsupported? Thoroughly explain your answer using the specific information listed, and propose and explain an alternate hypothesis (if necessary).

Explanation / Answer

Yes, the hyothesis stating that "cyanide inhibits an enzyme in the Krebs cycle" is correct. Cyanide inhibits cytochrome oxidase enzyme of the Kreb's cycle, so ATP is not formed in the mitochondria. The process of oxydative phosphorylation is blocked in cyanide poisoning thus, ATP cannot be generated, which is a characteristic metabolic alteration in cyanide poisoning. Cyanide has high affinity towards heam moiety of hemoglobin thus, making the cells not to use oxygen. Some of the tissues in our body such as brain and retina cannot synthesise ATP through anaerobic metabolism, people exposed to lethal doses of cyanide gas generally face coma and death.

In acute cyanide poisoning no other changes in metabolism can be identified as all other metabolic processes go normal. If the eath is delayed then high levels of glycolysis, puruvate levels ketoacidosis (due to impaired Kreb's cycle, pyruvate is not utilised and its levels become high, keto acidosis occur due to anaerobic metabolism) can be observed.

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