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BIOC Heme-Onc II > Pentose Phosphate Pathway > Flashcards

Pentose Phosphate Pathway Flashcards

1
Q

what are the molecules that make up the ROS (reactive oxygen species)?

what are the properties of each?

A
  • 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
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2
Q

which ROS is found at the mitochondrial ECT?

A

O2-

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3
Q

which ROS is lipid soluble?

A

H2O2

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4
Q

which ROS are found in X-rays? what can do they do?

A

OH0, O0

can split water into hydroxyl & hydrogen radicals

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5
Q

what is glutathione?

  • what is its function?
  • what does it require to carry out its function?
A

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
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6
Q

draw out the glutathione cycle

A
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7
Q

what are the branches of the PPP?

what is the purpose of each?

A
  • oxidative branch → provides NADPH. used for
    • FA synthesis
    • steroid synthesis
    • glutathione regeneration
  • non-oxidative branch → provides ribose. used for
    • nucleotide / nucleic acid synthesis
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8
Q

oxidative PPP branch

  • uses what starting material?
  • generates what final products? with what purpose?
A
  • starting material: glucose-6-phosphate (glycolytic intermediate)
  • final products:
    • NADPH: for glutathione cycle, FA / steroid synthesis
    • ribulose -5 - phosphate: enters non-oxidative PPP branch
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9
Q

draw out the steps of the oxidative PPP branch

A
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10
Q

non-oxidative PPP branch

  • uses what starting material?
  • generates what final products? with what purpose?
A
  • 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
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11
Q

outline the steps of the non-oxidative PPP branch

A
  • isomerase/epimerase rxn:
    • two ribulose-5-phosphate molecules converted two
      • ribose-5-P (isomerase rxn)
      • xylulose-5-P (epimerase rxn)
  • 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
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12
Q

the 1st step in the non-oxidative PPP branch requires

  • what reactants
  • what products
  • what enzymes
  • what cofactors?
A
  • reactant: ribulose-5-P
  • two enzymes used to make two products:
    • isomerase → ribose-5-P
    • epimerase → xyulose-5-P
  • cofactors - n/a
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13
Q

ribose 5-P isomerization

  • requires what enzyme?
  • involves what biochemical changes?
  • produces what product?
A
  • phospho-pentose isomerase
  • a ketone group (in ribulose) is converted to a aldehyde group (ribose)
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14
Q

ribose 5-P epimerization

  • requires what enzyme?
  • involves what biochemical changes?
  • produces what product?
A
  • phosphopentose epimerase
  • the orientation of an OH group is changed from the right in ribulose to left in xyulose
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15
Q

non-oxidative PPP - after ribose-5-P and xyulose-5-P are generated, what is the next step?

A

the first transketolase reaction

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16
Q

the first transketolase reaction of the non-oxidative PPP branch involves:

  • what reactants
  • what products?
  • what enzymes?
  • what co-factors?
  • what key biochemical changes?
A
  • 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)
17
Q

non-oxidative PPP - after glyceraldehyde-3-P and seo-heptulose-7-P are made, what is the next step?

A

the transaldolase reaction

18
Q

the transaldolase of the non-oxidative PPP branch involves:

  • what reactants?
  • what products?
  • what enzymes?
  • what co-factors?
  • what key biochemical changes?
A
  • 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)
19
Q

non-oxidative PPP - after erythrose-4-P and F-6-P are made, what is the next step?

A
  • F-6-P: fed into glycolysis
  • erythro-4-P: enters second ketolase reaction
20
Q

the second transketolase reaction of the non-oxidative PPP branch involves:

  • what reactants?
  • what products?
  • what enzymes?
  • what co-factors?
  • what key biochemical changes?
A
  • 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)
21
Q

ribose-5-phosphate

  • is made by what reaction?
  • is what kind of compound?
  • can enter what pathways?
A
  • 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
22
Q

what is true of both transketolase rxns non-oxidative PPP?

A
  • 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
23
Q

what is different about the transketolase reactions in non-oxidative PPP?

A
  • 1st rxn:
    • requires TPP (Vit B12)
    • produces sedoheptulose-7-P
  • 2nd rxn
    • produces fructose-6-P
24
Q

which non-oxidative PPP rxns produce glyceraldehyde-3-P?

A
  • 1st transketolase rxn (step 2)
  • 2nd transketolase rxn (final 4)
25
Q

which non-oxidative PPP rxns produce frucose-6-P?

A
  • the transaldolase rxn (3rd step)
  • the 2nd transketolase rxn (4th step
26
Q

discuss the regulation of the oxidative branch of PPP

A
  • rate limiting enzyme is glucose-6-phosphate dehydrogenase, which is
    • tightly regulated by NADPH (high NADPH inhibits G-6-P-DH)
27
Q

discuss the regulation of the non-oxidative branch of PPP

A
  • non-oxidative branch is reversible
    • direction of path depends on need for NADPH vs need for ribose
28
Q

what are the three “modes” of the PPP can run in?

what situations trigger which mode?

A

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
29
Q

describe mode 1 of PPP

when does mode 1 run?

A

need for ribose = need for NADPH

all paths run forward

30
Q

describe mode 2 of PPP

when does mode 2 of run?

A

non-oxidative branch runs backwards: glycolytic products → ribose-5-P

runs when need for ribose-5-P > need for NADPH

31
Q

describe mode 3 of the PPP

when does mode 3 of the PPP run?

A

glycolysis runs backwards to generate G-6-P to made NADPH

runs when need for NADPH > need for ribose

32
Q

G-6-PDH deficiency

  • inheritance pattern
  • demographics
  • pathogenesis
  • presentation
A
  • 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
33
Q

what drug can trigger anemia in a G-6-PDH deficient pt? how?

A

quinilones

  • are oxidative, an increase ROS in an RBC that without glutathione, a key anti-oxidant
34
Q

what does the glucaronic acid pathway produce?

A
  • glucuronic acid: structural molecule, inc molecule solubility
  • ascorbic acid: Vitamin seen only in humans
35
Q

what are the uses of glucuronic acid?

A
  • structure component of
    • GAGs
    • glycoproteins
  • increase solubility & thus the excretion of:
    • bilirubin (bilirubin glucuronic acid): toxic product of heme degradation
    • xenobiotics
36
Q

what does the glucuronic acid pathway require?

A
  • glucose-6-phosphate (starting material)
  • 2 NADH

BIOC Heme-Onc II (3 decks)

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