Pentose Phosphate Pathway Flashcards
General purpose of the PPP
Provides 5C sugars as precursors to make nucleotides (pentoses or phosphopentoses)
Also produces NADPH = reducing power for biosynthetic pathway…FAs, steroids, and NTs
Also protects membranes and tissues from oxidative damage and detoxifies xenobiotic durgs
Where are enzymes for PPP located
Cytosol
What do the following tissues use the PPP mainly for?
- Adrenal gland
- Liver
- Testes
- Adipose tissue
- Ovary
- Mammary gland
- RBCs
- Steroid syn
- FA and cholesterol syn
- Steroid syn
- FA syn
- Steroid syn
- FAS
- Maintenance of reduced glutathione
NADH vs. NADPH
NADH = donates electrons to the ETC, generating ATP by oxidative phosphorylation
NADPH = reducing power for biosynthetic pathways
Oxidative vs. nonoxidative PPP pathways
General
Oxidative = generates NADPH for biosynthetic pathways, and to counter the damaging effect of ROSs
Non-ox = recycles the pentose phosphate back to useful glycolytic intermediates…which are further metabolized
How many molecules of NADPH produced for every glucose molecule (actually G6P) to enter PPP
2 NADPH
Glucose 6P dehydrogenase (PPP)
Oxidative phase (reaction 1)
G6P —> 6-phosphoglucono-delta-lacton
NADPH is produced
‘Commitment step’
Under allosteric regulation by NADPH
Reversible
G6P comes from hexokinase reaction in glycolysis (glucokinase in liver)
Lactonase (PPP)
Oxidative phase / reaction 2
6-phosphoglucono-delta-lactone —> 6-phosphogluconate
Ring structure —> linear chain form
Irreversible
6-phosphogluconate dehydrogenase (PPP)
Oxidative phase / reaction 3
6-phosphogluconate —> D-ribulose-5P
Oxidative carboxylation (NADPH + CO2 produced)
Irreversible
Phosphopentose isomerase (PPP)
Oxidative / reaction 4
Ribulose-5P —> ribose-5P
Keto-sugar —> aldo-sugar
As needed ribose-5P = nucleotide precursor’
Reversible
Overall results of PPP
Glucose-6P —> ribose-5P
2 NADPH
1 CO2
Cell requirements that would dictate the need for the non-oxidative phase of PPP
Amount of NADPH required is much greater than the need for ribose-5P
Takes ribose-5P and makes useful intermediates for glycolysis or run through PPP again
The case for RBCs…since no nucleus
Epimerase (PPP)
Non-oxidative / reaction 1
Ribose-5P —> xylulose-5P
Aldose —> ketose sugar
X5P = regulatory molecule in carb and lipid metabolism
Transketolase (PPP)
Non-oxidative / reactions 2 and 4
Reaction 2:
Removes 2C from ribose-5P —> xylulose-5P
Result: 2 5C sugars —> 3C and 7C sugars
REQUIRES THIAMINE PYROPHOSPHATE (TPP, VITAMIN B1) as a cofactor
Reaction 4:
Removes 2C from ribose-5P (again) —> the 4C product from step #3
Results: 5C —> 3C (glyceraldehyde-3P)
4C —> 6C (fructose-6P)…which can be converted to G6P
Transaldolase (PPP)
Non-oxidative / reaction 3
Removes 3C from the 7C sugar and adds to the 3C sugar (both from step 2)
7C —> 4C (gets 2C in step 4)
3C —> 6C (F6P)
Does NOT need TPP as cofactor like transketolase
Allosteric regulation by NADPH on PPP
High NADPH inhibits glucose-6P dehydrogenase
First step in oxidative phase (commitment step)
If cell needs only steady supply of ribose-5P and no NADPH…
Oxidative phase is shut off
Instead the non-ox phase is run in the reverse direction using both F6P and glyceraldehyde3P to generate the phosphopentose
Role of xylulose-5P in control of carb and fat metabolism
After a high carb meal…
Levels of X5P rise via epimerase reaction in oxidative phase
Activates phosphoprotein phosphatase (PP2A)
Which dephosphorylates the PFK-2/FBPase-2 enzyme
Activates PFK-2 activity
Increases fructose-2,6-BP
Activates glycolysis…while inhibiting gluconeogenesis
….
Also boosts production of acetyl-CoA…the synthesis of NADPH (PPP) and Acetyl-Coa (PDH complex/glycolysis) both stimulate synthesis of FAs
NADPH requirement to reduce glutathione
RBCs need alot of NADPH for this purpose…to protect it from ROS
Glutathione exists in 2 forms
- Oxidized (GSSG)
- Reduced (2GSH - two molecules) - disulfide bond is broken
Glutathione and glutathione peroxidase function to reduce H2O2 —> H2O and O2…
2GSH —-> GSSG in the process (glut peroxidase reduces it back…needs NADPH for reducing power)
Drug-induced hemolytic anemia and favism
If something decreases G6PDH … NADPH levels can drop…depleting reduced GSH levels
—> drug-induced hemolytic anemia
G6PDH gene = X chromosome
G6PDH deficiency = most common enzymopathy
Anti-malaria drugs
Example = quinone
Can cause serious shit if have G6PDH deficiency
Symptoms of hemolytic crisis
Sudden rise in body temp
Yellow skin
Urine dark yellow - Hb in urine
Patient history = clue —> take sulfa drug? Or any other oxidative drug?
Alcoholics and hemolytic crisis
Can occur cause alcoholics can have a deficiency in TPP (cofactor for transketolase)
