The Pentose Pathway
The pentose pathway is an alternate pathway for the breakdown of glucose that produces NADPH instead of NADH
- NADPH is necessary for fatty acid synthesis and cholesterol synthesis (HMG CoA reductase), and to maintain globin
- conformation in RBC’s (keep glutathione reduced)
- also produces ribose, a five-carbon sugar necessary for nucleic acid synthesis
- present in most tissues; higher in embryonic/newborn than adult; occurs in the cytosol
Two segments:
- (1) Oxidative Pathway
– glucose-6-phosphate
Þ ribulose-5-phosphate – produces NADPH
(2) Non-oxidative Pathway – ribulose Þ glycolysis intermediates – no NADPH produced
Oxidative Pathway
- Two Enzymes:
- (1) Glucose-6P Dehydrogenase
- 100 million people are deficient in this enzyme
- deficiency leads to hemolysis
(2) Gluconate-6P Dehydrogenase
Total process produces 2 NADPH
- accounts for 50% of NADPH produced by body
- rest comes from malic enzyme (during fatty acid synthesis)
Ribulose-5-Phosphate Þ Ribose-5-Phosphate Þ Þ Þ Nucleotides/Nucleic Acids
Non-Oxidative Pathway
Essentially a series of rearrangements – produce one molecule of fructose-6P and two of glyceraldehyde-3P from three molecules of ribulose-5P
- transketolase
requires thiamine for its function – thiamine deficiency
Þ excess of ribulose, deficit of NADPH, neurological symptoms (Wernicke-korsakoff syndrome – alcohol induced)
glucose-2-C14 oxidation to C14O2 by RBCs can be used to detect thiamine deficiency The products can feed into the glycolytic pathway
alternatively, phosphoglucoisomerase can convert fructose-6P Þ glucose-6P – can cycle around
