Lecture 27: Pentose Phosphate Pathway Flashcards
Why do we need NADPH
Synthesis of monomers -Fatty acids -Cholesterol -Neurotransmitters -Nucleotides Reducing powers
Lactonase is what type of enzyme
Hydrolase
What is the rate limiting reaction in the oxidative phase of PPP
G6P–> Lactone (not specified which one)
Catalyzed by G6P dehydrogenase
Glutathione is a tripeptide of what amino acids
Glutamic acid
Cysteine
Glycine
Why is glutathione able to interact with proteins without an enzyme
Because of its disulfide bonds?
What is required for reduction of Glutathione
NADPH
Ratio of reduced Glutathione (GSH) to oxidized glutathione (GSSG) in normal cell
500:1
What other proteins besides G6PD can make NADPH
Isocitrate dehydrogenase
Malic enzyme
What is the most severe effect of G6PD deficiency
Liver cannot conjugate bilirubin, excessive amounts of bilirubin causes jaundice
G6PD can be a monomer, dimer and tetramer- which states are active/inactive, and what conditions favor those states
Monomer- Inactive- High NADPH, G6P, pH
Dimer- Active- High ionic strength, pH >8
Tetramer- Active- High NADP+, pH <6
Hsp27 interaction with G6PD
Promotes dimerization/activation
Activators of G6PD include
Dimerization
Transcription factors for antioxidant genes
Cell cycle and synthesis activators
Insulin
Inhibitors of G6PD include
Phosphorylation
Apoptosis-signaling proteins
The non oxidative phase of the PPP shuffles
Carbons
Ribose-5-phosphate isomerase
Part of shuffle 1
Converts Ribulose-5-phosphate to Ribose-5-phosphate
Ribulose-5-phosphate epimerase
Part of shuffle 1
Converts Ribulose-5-phosphate to Xylulose-5-phosphate
Transketolase
Shuffle 2
Transfers 2C from X5P, leaving behind Glyceraldehyde-3-phosphate
2C + Ribose-5-Phosphate–>Sedoheptulose-7-phosphate
2C + Erythrose-4-phosphate–> F6P
Transition state stabilized by TPP coenzyme
Transaldolase
Shuffle 3
Transfers 3C from Sedoheptulose-7-phosphate leaving behind Erythrose-4-phosphate
3C + Glyceraldehyde-3-phosphate –> F6P
Transition state stabilized by Lysine side chain
Shuffle 4, the final phase of the non-oxidative phase, regenerates what molecule using what pathway
Regenerates Glucose-6-Phosphate using gluconeogenesis pathway
Nucleotide synthesis mode
Nonoxidative mode in reverse
G3P and F6P both used to make Ribose-5-Phosphate
Balancing nucleotides and NADPH
G6P is converted to Ribose-5-Phosphate and NADPH is made
Anabolic needs
When primary need is for reducing power, fructose phosphates are converted into G6P for reoxidation in the oxidative phase
Primary product is NADPH
More power phase
When primary need is power and not much NADPH/pentose phosphates are needed, the reaction products (Gly-3-P) are used in glycolysis and Citric acid cycle
Why are G6PDD patients more likely to develop diabetes
Because high blood glucose levels will decrease expression of G6PD in pancreatic b-islet cells which produce insulin.
Which phase of PPP will be used if the cell needs NADPH as much as it needs R5P?
Oxidative phase only
If a cell is beginning to divide/replicate, which phase will be used
F6P and G3P go through reverse steps of non-oxidative phase of PPP to build R5P
In an adipose cell that is constantly building fatty acids, which phase/pathway will be used
Oxidative and non-oxidative steps will be performed
Gluconeogenesis will then be used to recycle F6P and G3P back to G6P in order to re-enter oxidative phase.
What pathways are used if the cell needs both ATP and NADPH
Oxidative and non-oxidative phase both used
Glycolytic intermediates GAP and F6P enter glycolysis for ATP and pyruvate formation
