WBR0979

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Author [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Serge Korjian)]]
Exam Type USMLE Step 1
Main Category Biochemistry
Sub Category General Principles
Prompt [[Prompt::Sorbitol concentration is measured in hepatocytes of normal rats and mutant rats with glucose intolerance. The aim of the experiment is to establish the association between the blood concentration of glucose and the concentration of sorbitol in hepatocytes. Shown below is a figure that illustrates sorbitol metabolism. Which compounds correspond to the cofactors X and Y, respectively?

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Answer A X=NADPH and Y=NAD+
Answer A Explanation NADPH and NAD+ are cofactors for aldose reductase and sorbitol dehydrogenase, respectively. Both enzymes and their cofactors are involved in sorbitol metabolism.
Answer B X=NAD+ and Y=NADPH
Answer B Explanation While both NAD+ and NADPH are needed for sorbitol metabolism, X corresponds to NADPH and Y corresponds to NAD+, and the order by which the enzymes and their cofactors function in the sorbitol pathway is important.
Answer C X=ATP and Y=NAD+
Answer C Explanation NADPH and NAD+ are cofactors for aldose reductase and sorbitol dehydrogenase, respectively. Both enzymes and their cofactors are involved in sorbitol metabolism. ATP is not a cofactor in either reaction.
Answer D X=NADPH and Y=ADP
Answer D Explanation NADPH and NAD+ are cofactors for aldose reductase and sorbitol dehydrogenase, respectively. Both enzymes and their cofactors are involved in sorbitol metabolism. ADP is not a cofactor in either reaction.
Answer E X=NAD+ and Y=ATP
Answer E Explanation NADPH and NAD+ are cofactors for aldose reductase and sorbitol dehydrogenase, respectively. Both enzymes and their cofactors are involved in sorbitol metabolism. ATP is not a cofactor in either reaction.
Right Answer A
Explanation [[Explanation::NADPH is the reduced form of NADP+ whereas NAD+ is the oxidized form of NADH. Both NADPH and NAD+ are cofactors are electron carriers and donors in the redox reactions of sorbitol metabolism. Glucose is converted to sorbitol by the action of aldose reductase (requires NADPH), and sorbitol is then converted to fructose by the action of sorbitol dehydrogenase (requires NAD+). While some cells are lacking sorbitol dehydrogenase (cells of the retina, Schwann cells, and kidney cells), other cells (e.g. hepatocytes and cells of the ovaries and seminal vesicles) have both enzymes to metabolize glucose into fructose.

Below is a figure that illustrates the metabolism of sorbitol

Educational Objective: NADPH and NAD+ are cofactors for aldose reductase and sorbitol dehydrogenase, respectively. Both enzymes and their cofactors are involved in sorbitol metabolism.
References: First Aid 2014 page 107]]

Approved Yes
Keyword NADPH, NAD+, Fructose, Cofactor, Sorbitol, Sorbitol metabolism, Sorbitol pathway, Diabetes
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