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Biochemistry Final Review > Ford (Pentose Phosphate Pathway) > Flashcards

Ford (Pentose Phosphate Pathway) Flashcards

1
Q

3 reactions of Oxidative Phase

A
  1. Glucose 6-Phosphate Dehydrogenase (G6P –> lactone) - form NADPH (RATE LIMITING STEP)
  2. Lactonase –> opens ring by adding water
  3. 6-Phosphogluconate Dehydrogenase (6PG –> ribulose 5 phosphate) - form NADPH
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2
Q

What do we need NADPH for?

A
  1. Synthesis of monomers (biosynthesis) - Anabolic

2. Reducing Power (detoxification)

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3
Q

Glutathione Structure

A

glutamatic acid-cysteine-glycine

  • glutamatic acid turned 90 degrees
  • cysteine = REDOX reactions
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4
Q

Glutathione Functions (3)

A
  1. Interaction with proteins (no enzymes needed)
    • disulfide bonds stabilize protein structure
  2. Inactivation of peroxides (Glutathione Peroxidase)
    • removes reactive oxygen species
  3. Regeneration of reduced glutathione (use NADPH)
    • uses glutathione reductase - regen. GSH
    • GSH does all the reacting
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5
Q

G6PD & Hemolytic Anemia

A
  • mutant G6PD have shortened lifetime
  • decreased G6PD activity –> dec. NADPH produced, dec. GSH produced, inc. ROS = HEMOLYSIS

RBCs diseases: metabolic errors, hemoglobinophathies, membrane/cytoskeleton, metabolic errors

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6
Q

G6PD & Neonatal Jaundice

A
  • most severe effect of G6PDD = blood is normal but liver CANNOT conjugate bilirubin
  • excessive amounts of unconjugated bilirubin causes JAUNDICE
  • bilirubin enters brain (kernicterus) = deafness, cerebral palsy, death
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7
Q

G6PD Monomer vs Tetramer

A

Monomer: favoring Hi NADPH, G6P, pH (INACTIVE)

Tetramer: favoring Hi NADP, low pH (less than 6) (ACTIVE)

NADP is both substrate and coenzyme

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8
Q

G6PD & Ataxia Telangiectasia

A
  • autosomal recessive mutation in ATM (progressive loss of coordination, sensitivity to mutagens)
  • ATM protein: controls rate of cell division, initiates DNA damage repair responses after DSBs (serine/threonine kinase) –> HSP27
  • HSP27: interacts w/G6PD, promotes dimerization
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9
Q

G6PD Regulation

A
  • transcription/translation, location in cell, post-translational controls
  • activators: dimerization, antioxidant genes (TF), cell cycle/synthesis activators, insulin
  • inhibitors: phosphorylation, apoptosis signaling genes
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10
Q

G6PD & Diabetes

A
  • insulin activates G6PD
  • inc. extracellular glucose stims G6PD in some cell types/inhibits in others
  • pancreatic B-islet cells: produce insulin, lost in diabetes, express low lvls of G6PD, hi external glucose = dec. G6PD
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11
Q

Nonoxidative Shuffle 1

A

Ribulose-5-phosphate isomerized to:

  • isomerase –> ribose-5-phosphate (tautomer)
  • epimerase –> xylulose-5-phosphate (epimer)
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12
Q

Nonoxidative Shuffle 2

A
  • transketolase transfers 2C from X5P (5C) leaving Glyceraldehyde-3-phosphate (3C)
  • to Ribose-5-phosphate = Sedoheptulose-7-phosphate
  • to Erythrose-4-phosphate = Fructose-6-phosphate

transition state stabilized by TPP coenzyme

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13
Q

Nonoxidative Shuffle 3

A

transaldolase transfers 3C units

  • from Sedoheptulose-7-phosphate = E4C
    • (transketolase substrate)
  • to Glyceraldehyde-3-phosphate = F6C
    • (same product as transketolase)

transition state stabilized by Lys sidechain

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14
Q

Nonoxidative Shuffle 4

A

regeneration of Glucose-6-phosphate

  • uses gluconeogenesis pathway
  • GAP –> F6P –> G6P –> glucose
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15
Q

Modes of Pentose Phosphate Pathway (4)

A
  1. Nucleotide Synthesis (G6P –> Ribose-5-phosphate)
    • make nucleotides
  2. Nucleotide/NADPH Synthesis (G6P –> R5P)
    • make nucleotides, generate 2 NADPH
  3. NADPH Synthesis
    • generates 2 NADPH from G6P –> R5P
  4. ATP Synthesis (GAP –> Pyruvate)
    • generates 2 ATP
    • primary products: F6P and GAP
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16
Q

Other proteins that can make NADPH (2)

A
  1. isocitrate dehydrogenase (3 enzymes, 2 use NADP)

2. malic enzyme (ME1) intercoverts malate and pyruvate in cytoplasm

17
Q

Primary Products of Pathway 4

A

Fructose-6-phosphate and GAP

18
Q

Primary Products of Pathway 3

A

NADPH

19
Q

Primary Products of Pathway 2

A

Ribose-5-phosphate and NADPH

20
Q

Primary Products of Pathway 1

A

Ribose-5-phosphate

Biochemistry Final Review (8 decks)

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