Pentose Phosphoate Pathway Flashcards

1
Q

where does the PPP start?

A

G6P enters the pathway

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2
Q

other names for PPP

A

hexose mono-pi pathway

phosphogluconate pathway

pentose shunt

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3
Q

list the 3 rxns of the oxidative phase

A

the oxidative phase makes NADPH

  1. G6P —-> lactone
  2. lactonase adds water
  3. 6-phosphogluonate —-> ribulose-5-pi
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4
Q

first rxn of oxidative phase

A

G6P —-> a lactone
***rate limiting step

G6P dehydrogenase

NADP+ is reduced to NADPH

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5
Q

2ND rxn of oxidative phase

A

lactonase is a hydrolase

it opens the ring by adding water

forming 6-phosphogluconate

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6
Q

3rd rxn of oxidative phase

A

6-phosphogluconate —> ribulose-5-pi
(oxidative decarboxylation)

6-phosphogluconate dehydrogenase

NADP+ reduced to NADPH

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7
Q

how is NADPH used?

A

used in catabolic and anabolic pathways

critical for ETC, oxphos, PPP

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8
Q

why do we need NADPH?

A
  1. synthesis of monomers for biosynthesis pathways

2. reducing power for detoxification

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9
Q

tissues w/ active PPP

A
adrenals
liver
testes
adipose
ovary, mammary
RBCs
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10
Q

structure of glutathione

A

a tripeptide
Gln-Cys-Gly

glutamine-cysteine-glycine

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11
Q

glutathione - enzymes

A

can interact w/ proteins w/o needing enzymes

disulfide bonds stabilize protein structure but only if made at proper locations

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12
Q

glutathione - peroxides

A

inactivation of peroxides requires glutathione peroxidase

helping to maintain the reactive oxygen species

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13
Q

glutathione - regeneration

A

regeneration of reduced glutathione uses NADPH

healthy cells have plenty NADPH, ratio maintained at 500:1
–if NADPH is under produced = problems

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14
Q

G6PDD

A

glucose-6-phosphate dehydrogenase deficiency

X-linked, recessive

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15
Q

G6PDD and hemolytic anemia

A

mutant G6PD has shortened lifetime
–Fe in heme must be reduced to bind O2

acute/induced anemias are temporary

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16
Q

other proteins that can make NADPH

A
  1. isocitrate dehydrogenase
    - -it has 3 isozymes
    - -2 of them use NADP+
  2. malic enzyme (ME1)
    - -it interconverts malate and pyruvate in the cytoplasm
17
Q

G6PDD and neonatal jaundice

A
  • -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

18
Q

Hsp27

A

interacts w/ G6PD

promotes G6PD dimerization

19
Q

G6PD regulation

A
  1. transcription/translation control
  2. location in cell
  3. post-translational controls

activators: dimerization, TFs for antioxidant genes, cell cycle and synthesis activators, insulin
inhibitors: phosphorylation, apoptosis-signaling proteins

20
Q

G6PD and diabetes

A

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

21
Q

nonoxidative phase - shuffle 1

A
  1. ribulose-5-pi isomerized to ribose-5-pi
    via
    ribose-5-pi isomerase
  2. ribulose-5-pi epimerase converts it to xylulose-5-pi
22
Q

nonoxidative phase - shuffle 2

A

transketolase transfers 2C from xylulose-5-pi to 2 options

also leaves behind glyceraldehyde-3-pi

transition state is stabilized by TPP coenzyme

23
Q

shuffle 2 - nonoxidative phase - 2 outcomes

A
  1. ribose-5-pi = sedoheptulose-7-pi

2. erythrose-4-pi = fructose-6-pi

24
Q

nonoxidative phase - shuffle 3

A

transaldolase transfers 3C units from (2 options)

transition state stabilized by Lys side chains

25
Q

shuffle 3 - 2 outcomes

A
  1. from sedoheptulose-7-pi to make transketolase substrate
    - –erythrose-4-pi left behind
  2. onto glyceraldehyde-3-pi making fructose-6-pi to make same product as transketolase
26
Q

nonoxidative phase - shuffle 4

A

regeneration of G6P

utilizes gluconeogenesis pathway

27
Q

what are the 4 outcomes based upon what the cell needs?

A

NADPH
energy
nucleotides
multiple things

28
Q

nucleotide synthesis needs

A

primary product is ribose-5-pi

produced from F6P or GAP
–nonoxidative phase in reverse

29
Q

balancing nucleotides and NADPH

A

primary product = ribose-5-pi + NADPH

G6P to ribulose-5-pi to ribose-5-pi
–also produces 2 NADPH

30
Q

anabolic needs – NADPH production

A

primary product = NADPH

utilizing the G6P to ribulose-5-pi conversion which produces 2 NADPH

31
Q

energy creation necessary

A

primary product = F6P + GAP

can use the products to create pyruvate to enter nrg pathways

GAP conversion to pyruvate produces 2 ATP