pentose phosphate pathway
Summary
The pentose phosphate pathway (PPP) is an alternative glucose oxidation pathway that generates NADPH for reductive biosynthesis and ribose-5-phosphate for nucleotide synthesis. It's critical for maintaining reduced glutathione levels and protecting cells from oxidative damage, particularly important in RBCs which lack other antioxidant systems.
Detail
The pentose phosphate pathway occurs in the cytoplasm and consists of two phases: the oxidative phase and the non-oxidative phase. The oxidative phase irreversibly converts glucose-6-phosphate to ribulose-5-phosphate, generating 2 NADPH molecules and CO2. The rate-limiting enzyme is glucose-6-phosphate dehydrogenase (G6PD). The non-oxidative phase reversibly interconverts sugar phosphates to regenerate glucose-6-phosphate or produce ribose-5-phosphate. NADPH serves crucial functions: maintaining glutathione in its reduced state (essential for neutralizing reactive oxygen species), providing reducing power for fatty acid synthesis, cholesterol synthesis, and steroid hormone production. The pathway is especially vital in tissues with high oxidative stress (RBCs, lens of eye) or active lipogenesis (liver, adipose tissue, mammary glands). G6PD deficiency, an X-linked disorder affecting 400+ million people worldwide, impairs the pathway's ability to generate NADPH, leading to hemolytic anemia when patients are exposed to oxidative stressors like certain drugs (primaquine, sulfonamides), foods (fava beans), or infections.
Sources
- Lippincott Illustrated Reviews: Biochemistry
- First Aid for the USMLE Step 1
- Harper's Illustrated Biochemistry
- Lehninger Principles of Biochemistry
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