Pentose Phosphate Pathway Flashcards
What does the PPP produce?
NADPH - reducing agent (electron donor) needed for biosynthesis and for reactions that are protective against oxidative damage.
Ribose-5-phosphate
Glucose-6-phosphate
In which tissues does the PPP occur most and why?
In tissues that are active in biosynthesis of fatty acids and cholesterol such as the liver, adrenal cortex, and lactating mammary glands.
In tissues that are more exposed to oxygen - cornea and red blood cells.
What is the rate-determining step of the PPP? What limits it?
The initial dehydrogenation of glucose-6-P catalyzed by glucose-6-phosphate dehydrogenase (G6PD). Limited by supply of NADP+, which this reaction hydrogenates into NADPH.
What are the respective roles of the oxidative and non-oxidative phases?
oxidative produces ribose-5-phosphate for nucleic acid production and synthesis of fatty acids and cholesterol and NADPH for reducing of harmful oxidizing agents.
non-oxidative process rearranges sugars produced by the oxidative process to reform glucose-6-phosphate for continuation of the oxidative pathway, as well as rearranging sugars for use in glycolysis.
What enzymes are involved in the non-oxidative pathway and what do they catalyze?
transaldolase and transketolase, which rearrange sugars
What is the importance of glucose-6-phosphate dehydrogenase (G6PD)?
Catalyzes the first reaction of the PPP, G6P into phosphogluconolactone, which will become ribose.
Also creates reducing agents (NADPH), which protect the cell from harmful oxidizing agents.
What are the characteristics of G6PD deficiency? why?
hemolytic anemia due to reactive oxygen species not being reduced and causing oxidative damage followed by hemolysis of RBCs
What is the distribution of G6PD deficiency and why?
Prevalent in the malaria belt due to partial protection against malaria.
Why are RBCs sensitive to mutations in G6PD?
They do not have a nucleus to replenish normal G6PD proteins, and the mutated type degrades over time (less stable), so when it is no longer present the RBC cannot make more, causing increased sensitivity to oxidative stress.
What is the role of NADPH in RBCs?
maintain the tripeptide glutathione (GSH) in its reduced state, which is used to detoxify reactive oxygen species.
NADPH is specifically used by glutathione reductase, an enzyme that returns glutathione peroxidase back into its reduced form after it reduces the oxidizing agent hydrogen peroxide or reacts with free radicals.
How does tripeptide glutathione (GSH) protect cells from oxidative damage?
- Reacts directly with free radicals.
2. the enzyme glutathione peroxidase uses two electrons from glutathione to reduce hydrogen peroxide to water.
