Enzyme inhibition: trivalent arsenic and lipoamide: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Enzyme inhibition: trivalent arsenic and lipoamide

Sample item

A farmer is brought after accidentally ingesting an arsenite-containing pesticide. He has vomiting, a garlic odour on his breath, hypotension and lactic acidosis, with high blood pyruvate and alpha-ketoglutarate. Inhibition of which group of enzymes best explains these biochemical findings?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, through binding to the dithiol of lipoamide

Trivalent arsenic binds vicinal sulfhydryls and therefore reduced lipoamide, the cofactor of the E2 component of PDH and alpha-ketoglutarate dehydrogenase. Pyruvate and alpha-ketoglutarate accumulate, lactate rises and ATP production falls. Dimercaprol, a dithiol, competes for the arsenic and is the antidote.

Option by option

  • A. Cytochrome c oxidase, through binding to the ferric heme

    Binding of heme iron in cytochrome oxidase is the action of cyanide, and it would not raise pyruvate and alpha-ketoglutarate selectively.

  • B. Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, through binding to the dithiol of lipoamide (correct)

    The dithiol of lipoamide is the target, explaining the raised pyruvate and alpha-ketoglutarate.

  • C. ATP synthase, through blocking the proton channel

    Blocking the F0 proton channel of ATP synthase is the action of oligomycin and does not involve sulfhydryl binding.

  • D. Aconitase, through conversion of the poison to fluorocitrate

    Aconitase inhibition by fluorocitrate follows fluoroacetate poisoning and raises citrate rather than alpha-ketoglutarate.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is B, Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, through binding to the dithiol of lipoamide. Trivalent arsenic binds vicinal sulfhydryls and therefore reduced lipoamide, the cofactor of the E2 component of PDH and alpha-ketoglutarate dehydrogenase.

Why is "Cytochrome c oxidase, through binding to the ferric heme" not the answer?

Binding of heme iron in cytochrome oxidase is the action of cyanide, and it would not raise pyruvate and alpha-ketoglutarate selectively.

Why is "ATP synthase, through blocking the proton channel" not the answer?

Blocking the F0 proton channel of ATP synthase is the action of oligomycin and does not involve sulfhydryl binding.

Why is "Aconitase, through conversion of the poison to fluorocitrate" not the answer?

Aconitase inhibition by fluorocitrate follows fluoroacetate poisoning and raises citrate rather than alpha-ketoglutarate.

What concept does this question test?

It tests Enzyme inhibition: trivalent arsenic and lipoamide in Biochemistry. Pyruvate and alpha-ketoglutarate accumulate, lactate rises and ATP production falls. Dimercaprol, a dithiol, competes for the arsenic and is the antidote.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Enzyme inhibition: trivalent arsenic and lipoamide?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.