Pentose phosphate pathway Flashcards
where does the PPP occur? what does it produce?
cytosol
-NADPH and Ribolose-5-phosphate
what molecules in the PPP are combined and used as intermediates in glycolysis? where do they enter glycolysis?
xylulose-5-phosphate (Xu5P) and ribulose-5-phosphate (R5P)
-join to make F6P and GAP
what are the roles of NADPH?
1) synthesis of molecules (cholesterol and FA)
2) prevention of oxidative damage
which tissues would you expect the PPP to be very active in? state whether this would be due to needs for synthesis of FA/cholesterol, protection against oxidative damage or synthesis of DNA
Synthesis of cholesterol /FA: Liver, adrenal glands, testes, mammary glands (tissues that make steroid hormones)
Oxidative protection (tissues exposed to O2): RBCs
DNA synthesis: rapidly dividing tissues
is the PPP normally active in skeletal muscle?
no, only if there is a lot of damage or high energy needs
what is the difference between NAD+ and NADP+? what part of the structure accepts electrons?
attachment of phosphate
-nicotinamide ring will accept electrons
what is the general role of NADH vs NADPH?
NADH favours oxidation
NADPH favours reduction
why does it make sense that the ratio of NAD+/NADH is ~1000 while NADP+/NAPH is ~0.01?
NAD+ is favoured in order to pull electrons to it (oxidize other molecules)
NADPH is favoured in order to reduce other molecules
in what other 2 rxns (other than PPP) can NADPH be produced?
isocitrate dehydrogenase + malic enzyme
what is the impact of ROS’s?
cause free radical oxidative stress
What is the master antioxidant? where is present in high levels?
Glutathione
-present at high levels in RBCs
what functional group is contained within glutathione that makes it the master antioxidant?
SH group
What is the role of glutathione peroxidase? what other molecules does this rxn generate?
Oxidizes glutathione from the reduced form to oxidized form
-watder and a FA hydroxyl group
what form do we want glutathione in? why? what catalyzes this rxn?
The reduced form, using glutathione reductase
-the reduced form is needed to work as an antioxidant
what cofactor is needed to reduce glutathione?
NADPH
how is the reduced vs oxidized form of glutathione written?
reduced: GSH
oxidized:GSSG
how many GSH produce how many GSSG?
2 GSH produce 1 GSSG
Explain the steps of the GSH redox cycle (include products, reactants and enzymes needed): what kind of metabolic pathway is this?
1: G6P converted into 6-phospho-gluconate, reducing NADP+ to NADPH
-uses G6P-dehydrogenase
2: GSSG is reduced to 2GSH molecules, oxidizing NADPH to NAD+
-uses glutathione reductase
3: Lipid peroxide (toxic) is converted to Lipid-OH (non-toxic), oxidizing GSH to GSSG
-uses glutathione peroxidase
this is an ETC
what enzyme is the most common mutation in the world?
G6P-dehydrogenase
what are the 2 major phases in the PPP? what are there roles?
Oxidative: produces majority of NADPH and R5P
Non-oxidative: provides flexibility through isomerization reactions depending on cellular demands
in the oxidative phase of the PPP, what 3 reactoins are seen? where does this also occcur?
1) oxidation
2) hydration
3) oxidaton + decarboxylation
-the last 3 steps of the CAC
what is the first oxidative rxn in the PPP? what enzyme is used? what is released? what is formed?
Oxidation of Glucose-6-phosphate to generate 6-phosphoglucono-lactone
-used glucose-6-phosphate dehydrogenase and produced NADH
what occurs in the second step of the oxidative phase? what enzyme is used? what is generated? what type of bond is formed?
Hydration of 6-phosphoglucono-lactone to generate 6-phosphogluconate, which contains an ester bond
-6-phosphogluconolactonase is used
what occurs in step 3 of the oxidative phase of the PPP? what enzyme is used? what is generated?
Oxidation of 6-phosphogluconate generates Ribulose-5-phosphate (RU5P), NADPH and CO2
-6-phosphogluconate dehydrogenase is used
what 2 enzymes IN the PPP generate NADPH?
1) glucose-6-phosphate dehydrogenase
2) phoshogluconate dehydrogenase
what is the overall rxn of the oxidative phase of the PPP?
what is the commited (most regulated) rxn in the PPP?
the first rxn to convert G6P to 6-phosphoglucanolactone
If Ru5P is isomerized, what molecule will it produce? what if it is epimerized? which is more common to be produced?
1) Ribose-5-phosphate (R5P)
2) Xylulose-5-phosphate (xu5P)
-Xu5P more common
how is F6P and GAP produced from R5P and Xu5P? how many of each molecule are needed and what is generated? how many C are lost and how many NADPH generated?
through a series of reversibe rearrangements of the carbon bonds
-3G6P generate 2Xu5P and 1R5P which generate 2F6P and 1 GAP (3 CO2 lost and 6 NADPH generated)
explain the overview of F6P and GAP generation? what do we start with, what do we end with?
1) start with 3 6C molecules
2) they get converted to 5C moleucles (2 Xu5P and 1 R5P) - 3CO2 are lost and 6NADPH made
3) production of 2F6P and 1GAP moleucle
what determines the pathway thate G6P will go to? what 3 pathways can it take in the PPP?
The cellular requirments
1) Nucleotide synthesis
-Production of R5P to make nucleotides
2) NADPH synthesis
-in cells that need large amounts of NADPH for reductive biosynthesis (cholesterol /FA) or to combat oxidative stress; F6P and GAP go through gluconeogenesis to make more NADPH
3) Energy generation and NADPH synthesis
-Provides NADPH and glycolysis / CAC intermediates for energy in tissues that need both
how is the PPP primarly regulated?
Regulated by the rate of G6P dehydrogenase
-substrate availibilty (NADP+)
what stimulates the synthesis of G6P dehydrogenase?
insulin
is product inhibition a way to regulate the PPP? why or why not?
no, there is no product inhibition because NADPH levels would never become high
how do tumours influence glycolytic enzymes and transporters? what happens to the PPP?
glucose transporters and glycolytic enzymes are overproduced
-the PPP activity is increasedd in rapidly dividing cells (cancer cells)
