Carbohydrate metabolism: metformin and lactate: 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 · Carbohydrate metabolism: metformin and lactate

Sample item

A 68-year-old man with type 2 diabetes and an estimated GFR of 18 mL/min, who is still taking metformin, presents with vomiting, hyperventilation and a pH of 7.12. Lactate is 11 mmol/L and the anion gap is raised. Which mechanism most directly accounts for the lactate accumulation?

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

The answer and the reasoning

D. Inhibition of mitochondrial complex I and of hepatic gluconeogenesis from lactate

Metformin inhibits mitochondrial respiratory complex I and the mitochondrial glycerophosphate shuttle, increasing the NADH to NAD+ ratio and blocking hepatic conversion of lactate to glucose. Accumulation in renal failure raises plasma drug levels and tips the balance to lactic acidosis. Metformin is contraindicated at very low GFR.

Option by option

  • A. Activation of pyruvate dehydrogenase leading to excess acetyl-CoA

    Pyruvate dehydrogenase activation would reduce lactate, not raise it.

  • B. Inhibition of the pentose phosphate pathway in red cells

    Pentose phosphate pathway inhibition does not produce lactic acidosis and is unrelated to metformin.

  • C. Stimulation of glucose-6-phosphatase causing futile cycling

    Increased glucose-6-phosphatase activity would raise glucose output, whereas metformin lowers hepatic glucose production.

  • D. Inhibition of mitochondrial complex I and of hepatic gluconeogenesis from lactate (correct)

    Correct. Reduced oxidative capacity and impaired lactate gluconeogenesis lead to lactic acidosis in renal failure.

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 D, Inhibition of mitochondrial complex I and of hepatic gluconeogenesis from lactate. Metformin inhibits mitochondrial respiratory complex I and the mitochondrial glycerophosphate shuttle, increasing the NADH to NAD+ ratio and blocking hepatic conversion of lactate to glucose.

Why is "Activation of pyruvate dehydrogenase leading to excess acetyl-CoA" not the answer?

Pyruvate dehydrogenase activation would reduce lactate, not raise it.

Why is "Inhibition of the pentose phosphate pathway in red cells" not the answer?

Pentose phosphate pathway inhibition does not produce lactic acidosis and is unrelated to metformin.

Why is "Stimulation of glucose-6-phosphatase causing futile cycling" not the answer?

Increased glucose-6-phosphatase activity would raise glucose output, whereas metformin lowers hepatic glucose production.

What concept does this question test?

It tests Carbohydrate metabolism: metformin and lactate in Biochemistry. Accumulation in renal failure raises plasma drug levels and tips the balance to lactic acidosis. Metformin is contraindicated at very low GFR.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. 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 Carbohydrate metabolism: metformin and lactate?

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.