Pentose Phosphate Pathway Flashcards
what are the molecules that make up the ROS (reactive oxygen species)?
what are the properties of each?
- O2- (superoxide dismutase)
- highly reactive
- mostly seen at ECT
- H202 (hydrogen peroxidase)
- weak oxidizing agents
- lipid soluble
- OH0 / O0
- high energy radiations - seen in X-rays
- can split water into hydroxyl + hydrogen radicals
which ROS is found at the mitochondrial ECT?
O2-
which ROS is lipid soluble?
H2O2
which ROS are found in X-rays? what can do they do?
OH0, O0
can split water into hydroxyl & hydrogen radicals
what is glutathione?
- what is its function?
- what does it require to carry out its function?
an antioxidant
- function: neutralizes ROS hydrogen peroxide (H202) by converting it into water (H20)
- must be in its reduced form (2G-SH) to function, which requires
- FADH2
- NADPH - made by oxidizing portion
draw out the glutathione cycle
what are the branches of the PPP?
what is the purpose of each?
-
oxidative branch → provides NADPH. used for
- FA synthesis
- steroid synthesis
- glutathione regeneration
-
non-oxidative branch → provides ribose. used for
- nucleotide / nucleic acid synthesis
oxidative PPP branch
- uses what starting material?
- generates what final products? with what purpose?
- starting material: glucose-6-phosphate (glycolytic intermediate)
- final products:
- NADPH: for glutathione cycle, FA / steroid synthesis
- ribulose -5 - phosphate: enters non-oxidative PPP branch
draw out the steps of the oxidative PPP branch
non-oxidative PPP branch
- uses what starting material?
- generates what final products? with what purpose?
- starting materials: ribulose-5-phosphate (from oxidative PPP branch)
- finals products:
- ribose - 5- phosphate: used for nucleic acid / nucleotide synthesis
- glycolytic intermediates (G-3-P, F-6-P): are returned to glycolysis
outline the steps of the non-oxidative PPP branch
-
isomerase/epimerase rxn:
- two ribulose-5-phosphate molecules converted two
- ribose-5-P (isomerase rxn)
- xylulose-5-P (epimerase rxn)
- two ribulose-5-phosphate molecules converted two
-
1st transketolase rxn:
- ribose-5-P + xylulose-5-P → glyceraldehyde 3-P+ sedoheptulose-7-P
-
transaldolase rxn:
- glyceraldehyde-3-P + sedoheptulose-7-P → erythrose-4-P+ F-6-P
-
2nd transketolase rxn:
- erythrose-4-P + xyulose-5-P → glyceraldehyde-3-P + F-6-P
the 1st step in the non-oxidative PPP branch requires
- what reactants
- what products
- what enzymes
- what cofactors?
- reactant: ribulose-5-P
- two enzymes used to make two products:
- isomerase → ribose-5-P
- epimerase → xyulose-5-P
- cofactors - n/a
ribose 5-P isomerization
- requires what enzyme?
- involves what biochemical changes?
- produces what product?
- phospho-pentose isomerase
- a ketone group (in ribulose) is converted to a aldehyde group (ribose)
ribose 5-P epimerization
- requires what enzyme?
- involves what biochemical changes?
- produces what product?
- phosphopentose epimerase
- the orientation of an OH group is changed from the right in ribulose to left in xyulose
non-oxidative PPP - after ribose-5-P and xyulose-5-P are generated, what is the next step?
the first transketolase reaction
the first transketolase reaction of the non-oxidative PPP branch involves:
- what reactants
- what products?
- what enzymes?
- what co-factors?
- what key biochemical changes?
- enzyme: transketolase
- co-factors: TPP (Vitamin B1)
- biochemical change: transfer of 2-carbon unit from a ketose group (xyulose-5-P) to a aldose group (ribose-5-P)
non-oxidative PPP - after glyceraldehyde-3-P and seo-heptulose-7-P are made, what is the next step?
the transaldolase reaction
the transaldolase of the non-oxidative PPP branch involves:
- what reactants?
- what products?
- what enzymes?
- what co-factors?
- what key biochemical changes?
- enzymes - transaldolase
- coenzymes - n/a
- biochemical changes: a 3 carbon unit is transferred from a ketose (sedoheptoulose-7-P) to a aldose (glyceraldehyde-3-P)
non-oxidative PPP - after erythrose-4-P and F-6-P are made, what is the next step?
- F-6-P: fed into glycolysis
- erythro-4-P: enters second ketolase reaction
the second transketolase reaction of the non-oxidative PPP branch involves:
- what reactants?
- what products?
- what enzymes?
- what co-factors?
- what key biochemical changes?
- enzymes - transketolase
- cofactors - n/a
- biochemical changes: a 2 carbon group is transferred from a ketose (xyulose-5-phosphate) to a aldose (erythrose-4-phosphate)
ribose-5-phosphate
- is made by what reaction?
- is what kind of compound?
- can enter what pathways?
- made by 1st step of non-oxidative PPP: isomerization reaction
- is a aldose
- can either
- continue with non-oxidative PPP by entering 1st transketolase rxn, or
- enter nucleic acid / nucleotide synthesis pathway
what is true of both transketolase rxns non-oxidative PPP?
- require transketolase enzyme
- involve xyulose-5-phosphate as a substrate
- involve transfer of 2 carbon unit from a ketose to an aldose (ketose = xyulose)
- produce glyceraldehyde-3-P
what is different about the transketolase reactions in non-oxidative PPP?
- 1st rxn:
- requires TPP (Vit B12)
- produces sedoheptulose-7-P
- 2nd rxn
- produces fructose-6-P
which non-oxidative PPP rxns produce glyceraldehyde-3-P?
- 1st transketolase rxn (step 2)
- 2nd transketolase rxn (final 4)
which non-oxidative PPP rxns produce frucose-6-P?
- the transaldolase rxn (3rd step)
- the 2nd transketolase rxn (4th step
discuss the regulation of the oxidative branch of PPP
- rate limiting enzyme is glucose-6-phosphate dehydrogenase, which is
- tightly regulated by NADPH (high NADPH inhibits G-6-P-DH)
discuss the regulation of the non-oxidative branch of PPP
- non-oxidative branch is reversible
- direction of path depends on need for NADPH vs need for ribose
what are the three “modes” of the PPP can run in?
what situations trigger which mode?
based on direction of non-oxidative path, oxidative path, and glycolysis
- mode 1 - need for ribose = need for NADPH
- all paths run in forward direction
- mode 1 - need for ribose > need for NADPH
- non-oxidative path runs backwards: glycolytic products → ribose
- mode 3 - need for NADPH > need for ribose
- glycolytic path runs backward: ends products → G-6-P → NADPH
describe mode 1 of PPP
when does mode 1 run?
need for ribose = need for NADPH
all paths run forward
describe mode 2 of PPP
when does mode 2 of run?
non-oxidative branch runs backwards: glycolytic products → ribose-5-P
runs when need for ribose-5-P > need for NADPH
describe mode 3 of the PPP
when does mode 3 of the PPP run?
glycolysis runs backwards to generate G-6-P to made NADPH
runs when need for NADPH > need for ribose
G-6-PDH deficiency
- inheritance pattern
- demographics
- pathogenesis
- presentation
- inheritance pattern = X-linked
- demographics
- almost exclusively male
- AA
- pathogenesis: oxidative PPP branch disruption
- no oxidative PPP branch → NADPH → no glutathione regeneration → accumulation of ROS (H202) → RBC lysis → hemolytic anemia
- often triggered by an increase in oxidative nature of environment
- ex - quinolone
- presentation - hemolytic anemia
what drug can trigger anemia in a G-6-PDH deficient pt? how?
quinilones
- are oxidative, an increase ROS in an RBC that without glutathione, a key anti-oxidant
what does the glucaronic acid pathway produce?
- glucuronic acid: structural molecule, inc molecule solubility
- ascorbic acid: Vitamin seen only in humans
what are the uses of glucuronic acid?
-
structure component of
- GAGs
- glycoproteins
-
increase solubility & thus the excretion of:
- bilirubin (bilirubin glucuronic acid): toxic product of heme degradation
- xenobiotics
what does the glucuronic acid pathway require?
- glucose-6-phosphate (starting material)
- 2 NADH
