Pentose Phosphate Pathway Flashcards
What is the pentose phosphate pathway?
Oxidation of glucose 6-phosphate to pentose phosphates
What are the two phases of the pentose phosphate pathway?
- The oxidative phase: involves oxidation reduction (dehydrogenases)
- The nonoxidative phase: goal is to regenerate glucose 6-phosphate
What are the two important products of the pentose phosphate pathway?
- Ribose 5 phosphate: makes DNA and RNA
- NADPH: useful if the cell is going to face oxidative damage caused by free radicals
How many steps are in the oxidative phase of the pentose phosphate pathway
4 steps
Describe the first step in oxidative phase of the pentose phosphate pathway
Oxidation of glucose 6-phosphate by glucose 6-phosphate dehydrogenase to form 6-phospho-glucono-δ-lactone
First molecule of NADPH is generated
What is the role of NADP+ in the first step of the oxidative phase of the pentose phosphate pathway?
NADP+ acts as the electron acceptor
The pentose phosphate pathway is unable to proceed without NADP+ as the electron acceptor
Describe the second step in oxidative phase of the pentose phosphate pathway
Lactonase hydrolyzes 6-phospho-glucono-δ-lactone to 6-phosphogluconate
Describe the third step in oxidative phase of the pentose phosphate pathway
6-phosphogluconate undergoes oxidation and decarboxylation by 6-phosphogluconate dehydrogenase to form ketopentose ribulose 5-phosphate
Second molecule of NADPH = generated
Describe the fourth step in oxidative phase of the pentose phosphate pathway
Phosphopentose isomerase converts ribulose 5-phosphate to its aldose isomer ribose 5-phosphate
Describe the first step of the nonxidative phase of the pentose phosphate pathway
- Epimerization / Transketolase
- Ribulose 5-phosphate is epimerized to xylulosze 5-phosphate
- Part of xylulose 5-phospahte gets broken and stitched to ribose 5-phosphate in a transketolase reaction (TPP = a cofactor)
- The new products are glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate
What is the significance of TPP
- TPP facilitates the making and breaking of carbon-carbon bonds by stabilizing the carbanion intermediate
Describe the second step of the nonxidative phase of the pentose phosphate pathway
- Transaldolase
- A three carbon fragment is removed from sedoheptulose 7-phosphate and condensed with glyceraldehyde 3-phosphate
- The new products are erythrose 4-phosphate and xylulosze 5-phosphate
*Carbanion intermediate is stabilized by Lysine (protonated Schiff base)
Describe the third step of the nonxidative phase of the pentose phosphate pathway
- Transketolase (again!)
- erythrose 4-phosphate and xylulosze 5-phosphate combine
- The new products are fructose 6-phosphate and glyceraldehyde 3-phosphate
- Catalyzed by TPP
How can NADPH regulate the use of glucose 6-phosphate in either the pentos phosphate pathway or glycolysis through feedback inhibition?
- Glucose 6-phosphate = partitioned between glycolysis and pentose phosphate pathway
- Whether glucose 6-phosphate ends up in the pentose phosphate pathway or glycolysis depends on what the cell need and the concentration of NADPH in the cytosol
- Too much NADPH (low NADP+) will stop the pentos phosphate pathway and glucose 6-phosphate will be used for glycolysis
- Low NADPH (high NADP+) will increase the flow of glucose 6-phosphate through the pentose phosphate pathway
Why wouldn’t Pythagoras eat falafel?
- Pythagoras had a glucose-6-phosphate dehydrogenase deficiency which is needed in the first step of the Pentos phosphate pathway
- Falafel = made from fava beans
- Fava beans contain a molecule called divicine which reacts with oxygen to form superoxide radical which can then form hydrogen peroxide
- Hydrogen peroxide is typically converted to water by glutathione peroxidase (which uses reduced glutathione (GSH)) BUT if this does not happen hydroxyl free radicals will form and cause a lot of damage
- Glutathione reductase generates GSH from its oxidized form (GSSG)
- Glutathione reductase cannot function without NADPH (produced in the first step of the Pentos phosphate pathway)