Metabolism: The pentose phosphate pathway and G6PD deficiency

The pentose phosphate pathway (PPP) can be divided into two phases, as shown in Figure 1. The oxidative phase is crucial for producing NADPH, which essential for both biosynthetic processes and antioxidant defenses. This phase regenerates glutathione into its active forms (GSH), enabling GSH to neutralize reactive species like hydrogen peroxide (H

_{2}

_{2}

) and combat oxidative stress within cells. The nonoxidative phase comprises a series of reversible reactions catalyzed by enzymes such as transketolase and transaldolase; these reactions facilitate the rearrangement of carbon atoms among various sugar phosphates, generating critical metabolic intermediates like glyceraldehyde-3-phosphate and fructose-6-phosphate. The rate limiting enzyme of the oxidative phase is glucose-6-phosphate dehydrogenase (G6PD).

Figure 1 The pentose phosphate pathway

To investigate how disrupting the PPP impacts a cell’s ability to grow and reproduce, researchers used cloning efficiency assays with cells that were modified to not express G6PD (“G6PD null cells”). A cloning efficiency assay quantifies the ability of a single cell to replicate and produce a colony of cells; cloning efficiency (%) equals the percentage of plated cells that produce colonies. Figure 2 shows the mean cloning efficiency for control and G6PD null cells under different oxygen conditions.

Figure 2 Mean cloning efficiency for control and G6PD null cells

Researchers further assessed cloning efficiency after exposing cells to increasing levels of diamide, a sulfhydryl containing compound that depletes GSH in the cell. Figure 3 shows the mean cloning efficiency for control and G6PD null groups exposed to varying concentrations of diamide.

Figure 3 Mean cloning efficiency for control and G6PD null cells

Pandolfi, P. P., Sonati, F., Rivi, R., Mason, P., Grosveld, F., & Luzzatto, L. (1995). Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress. EMBO J, 14(21), 5209-5215.

Which of the following hypotheses best explains results shown in Figure 2?

(Choice A)
Absence of the rate-limiting enzyme of the pentose phosphate pathway sensitizes cells to harmful oxidative stress.
(Choice B)
Absence of the rate-limiting enzyme of the pentose phosphate pathway prevents production of electron-acceptor molecules.
(Choice C)
Absence of the rate-limiting enzyme of the pentose phosphate pathway prevents synthesis of nucleotides needed for cell division.
(Choice D)
Absence of the rate-limiting enzyme of the pentose phosphate pathway prevents synthesis of lipids needed for cell division.

MCAT

Course: MCAT > Unit 2

Problem