Pathway Pentose Phosphate Pathway (Erythrocyte)

A simplified diagram to show the role of G6PD in generating NADPH in red blood cells - this can then be utilized in the Oxidative Stress Regulatory and Methylene Blue Pathways.
Pentose Phosphate Pathway (Erythrocyte)
g6pd pgd hk1 gpi oxidative pathway Methylene pathway pgls
clickable pathway icons


The Pentose Phosphate Pathway (PPP) and production of NADPH in red blood cells

Glucose is converted to glucose-6-phosphate by hexokinase (HK1), and then enters either the glycolysis pathway via conversion to the isomer fructose-6-phosphate, or the PPP (also known as hexose monophosphate shunt) via oxidation into 6-phosphogluconolactone [Articles:18177777, 16204390, 21376665, 18226191, 17489100, 13799836, 15862084, 9531504]. Two steps within the PPP produce NADPH; the conversion of glucose-6-phosphate to 6-phosphogluconolactone by G6PD, and 6-phosphogluconate to ribulose-5-phosphate by 6-phosphogluconate dehydrogenase (PGD, 6PGD) [Articles:18177777, 16204390, 18226191, 21376665, 20350285]. The end product of the pathway is ribose-5-phosphate, utilized for the production of nucleotides, polysaccharides and coenzymes, and used in RBCs for phosphoribosylpyrophosphate (PRPP) production to generate ADP for use in the Embden-Meyerhof glycolysis pathway [Articles:21376665, 20122995, 7713590]. NADPH is required in the RBC for the regulation of oxidative stress and within the methylene blue pathway [Articles:21376665, 7489710, 7073040]. The only source of NADPH in RBCs is via the PPP, in which G6PD is the rate-limiting step [Articles:16204390, 2633878, 18177777, 4154443, 15862084, 21376665]. As RBCs age, enzyme activities involved in glucose metabolism diminish, including G6PD, reducing energy production and ability to protect cell membrane integrity and hemoglobin from oxidation [Articles:14074568, 13799836].

Authors: Ellen M. McDonagh, José M. Bautista, Ilan Youngster, Russ B. Altman, Teri E. Klein.
McDonagh Ellen M, Bautista José M, Youngster Ilan, Altman Russ B, Klein Teri E. "PharmGKB summary: methylene blue pathway" Pharmacogenetics and genomics (2013).
If you would like to reproduce this PharmGKB pathway diagram, please acknowledge the copyright to PharmGKB and state that permission has been given by PharmGKB and Stanford University. Also, please send a brief email to to inform us of which pathway diagram you are using and for what purpose.
Therapeutic Categories:
  • Physiological mechanisms

Entities in the Pathway

Genes (5)

Relationships in the Pathway

Arrow FromArrow ToControllersPMID
6-phosphogluconate Ribulose-5-phosphate PGD 18177777, 18226191
6-phosphogluconolactone 6-phosphogluconate PGLS 10518023, 11457850
Fructose-6-phosphate Glucose-6-phosphate 18226191, 21376665
Glucose Glucose-6-phosphate HK1 13799836, 16204390, 18177777, 21376665
Glucose-6-phosphate 6-phosphogluconolactone G6PD 16204390, 18177777, 18226191, 20350285, 21376665
Glucose-6-phosphate Fructose-6-phosphate GPI 13799836, 18226191, 21376665
NADP NADPH PGD 18177777, 18226191
NADP NADPH G6PD 16204390, 18177777, 18226191, 20350285, 21376665
Ribulose-5-phosphate Ribose-5-phosphate
Glucose transporters 15862084
transporters Glucose

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