Erythroblasts isolated from a bone marrow biopsy sample of a patient with neonatal jaundice are incubated in a medium containing radiolabeled glucose. The cells are unable to generate NADPH from glucose metabolism but are able to convert fructose-6-phosphate to ribose-5-phosphate, which is required for nucleic acid synthesis. Which of the following enzymes is essential for the latter conversion?

Question

Erythroblasts isolated from a bone marrow biopsy sample of a patient with neonatal jaundice are incubated in a medium containing radiolabeled glucose.  The cells are unable to generate NADPH from glucose metabolism but are able to convert fructose-6-phosphate to ribose-5-phosphate, which is required for nucleic acid synthesis.  Which of the following enzymes is essential for the latter conversion?

Quizplus · Accepted Answer

11ec160b_369d_6a6e_9249_3d0cafe737fb_MD0001_00 The pentose phosphate pathway (HMP shunt) generates NADPH for use in reductive reactions and ribose-5-phosphate, a precursor for the synthesis of nucleotides. The pathway consists of 2 types of reactions, oxidative (irreversible) and nonoxidative (reversible), both of which can function independently depending on cellular requirements. Activity of the nonoxidative reactions is governed by the cellular demand for ribose-5-phosphate. When ribose-5-phosphate is produced in excess, transketolase and transaldolase can produce the glycolytic intermediates glyceraldehyde-3-phosphate and fructose-6-phosphate for ATP generation. When ribose-5-phosphate demand exceeds the production capabilities of the oxidative pathway, the nonoxidative pathway functions in reverse and transketolase and transaldolase catalyze the conversion of fructose-6-phosphate and glycerldehyde-3-phosphate to ribose-5-phosphate. (Choice A) Aconitase catalyzes the isomerization of citrate to isocitrate in the citric acid cycle. (Choice B) Enolase catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis. (Choice C) Glucose-6-phosphate dehydrogenase catalyzes the initial and rate-limiting step of the pentose phosphate pathway. Deficiency of this enzyme results in hemolytic anemia due to the inability to generate NADPH in the oxidative portion of the pathway. However, nonoxidative reactions are responsible for conversion of fructose-6-phosphate to ribose-5-phosphate. (Choice D) Glutathione reductase catalyzes the reduction of glutathione disulfide to glutathione using NADPH. Glutathione aids red blood cells in resisting oxidative stress. Educational objective: The pentose phosphate pathway consists of an oxidative (irreversible) branch and a nonoxidative (reversible) branch, and each can function independently based on cellular requirements. Transketolase, an enzyme of the nonoxidative branch, is responsible in part for the interconversion of ribose-5-phosphate (nucleotide precursor) and fructose-6-phosphate (glycolytic intermediate). __________ References: The pentose phosphate pathway and cancer. (http://www.ncbi.nlm.nih.gov/pubmed/25037503)

Erythroblasts Isolated from a Bone Marrow Biopsy Sample of a Patient