Pentose Phosphoate Pathway Flashcards
where does the PPP start?
G6P enters the pathway
other names for PPP
hexose mono-pi pathway
phosphogluconate pathway
pentose shunt
list the 3 rxns of the oxidative phase
the oxidative phase makes NADPH
- G6P —-> lactone
- lactonase adds water
- 6-phosphogluonate —-> ribulose-5-pi
first rxn of oxidative phase
G6P —-> a lactone
***rate limiting step
G6P dehydrogenase
NADP+ is reduced to NADPH
2ND rxn of oxidative phase
lactonase is a hydrolase
it opens the ring by adding water
forming 6-phosphogluconate
3rd rxn of oxidative phase
6-phosphogluconate —> ribulose-5-pi
(oxidative decarboxylation)
6-phosphogluconate dehydrogenase
NADP+ reduced to NADPH
how is NADPH used?
used in catabolic and anabolic pathways
critical for ETC, oxphos, PPP
why do we need NADPH?
- synthesis of monomers for biosynthesis pathways
2. reducing power for detoxification
tissues w/ active PPP
adrenals liver testes adipose ovary, mammary RBCs
structure of glutathione
a tripeptide
Gln-Cys-Gly
glutamine-cysteine-glycine
glutathione - enzymes
can interact w/ proteins w/o needing enzymes
disulfide bonds stabilize protein structure but only if made at proper locations
glutathione - peroxides
inactivation of peroxides requires glutathione peroxidase
helping to maintain the reactive oxygen species
glutathione - regeneration
regeneration of reduced glutathione uses NADPH
healthy cells have plenty NADPH, ratio maintained at 500:1
–if NADPH is under produced = problems
G6PDD
glucose-6-phosphate dehydrogenase deficiency
X-linked, recessive
G6PDD and hemolytic anemia
mutant G6PD has shortened lifetime
–Fe in heme must be reduced to bind O2
acute/induced anemias are temporary
other proteins that can make NADPH
- isocitrate dehydrogenase
- -it has 3 isozymes
- -2 of them use NADP+ - malic enzyme (ME1)
- -it interconverts malate and pyruvate in the cytoplasm
G6PDD and neonatal jaundice
- -most severe effect of G6PDD
- -blood is normal but liver cannot conjugate bilirubin
- -excessive amounts of unconjugated bilirubin causes jaundice
when bilirubin enters the brain (kernicterus) deafness, cerebral palsy, death
Hsp27
interacts w/ G6PD
promotes G6PD dimerization
G6PD regulation
- transcription/translation control
- location in cell
- post-translational controls
activators: dimerization, TFs for antioxidant genes, cell cycle and synthesis activators, insulin
inhibitors: phosphorylation, apoptosis-signaling proteins
G6PD and diabetes
insulin activates G6PD
increases in EC glucose can stim G6PDD in some cells but inhibit in others
pancreatic B-islet cells particularly susceptible which is why G6PDD patients are likely to develop diabetes
nonoxidative phase - shuffle 1
- ribulose-5-pi isomerized to ribose-5-pi
via
ribose-5-pi isomerase - ribulose-5-pi epimerase converts it to xylulose-5-pi
nonoxidative phase - shuffle 2
transketolase transfers 2C from xylulose-5-pi to 2 options
also leaves behind glyceraldehyde-3-pi
transition state is stabilized by TPP coenzyme
shuffle 2 - nonoxidative phase - 2 outcomes
- ribose-5-pi = sedoheptulose-7-pi
2. erythrose-4-pi = fructose-6-pi
nonoxidative phase - shuffle 3
transaldolase transfers 3C units from (2 options)
transition state stabilized by Lys side chains
