Fig 173

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Fig 17-3
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During study of pathways pay attention to

• 1) Changes in structures of intermediates (esp.
  in carbon skeleton and in oxidation states of C
  atoms).
• 2) Phosphate group transfer.
• 3) Electron transfer
• (to/from NAD/NADH etc.)

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TCA cycle ox. phosphorylation
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Hexokinase reaction

• C6 hydroxyl group attacks g-phospate of ATP
  (direct phosphate group transfer).
• Logic
• ATP consumption increases glucose transport into
  cell
• G-6-P is first intermediate in several pathways

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Phosphoglucose isomerase reaction

• 1,2 carbonyl shift via enediolate intermediate
• Logic
• This sets up the aldolase reaction to yield two
  C3 species

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Phosphofructokinase reaction

• Direct attack of 1 hydroxyl on g-phosphate of
  ATP
• Logic
• This is the committed step for the glycolytic
  pathway (site of regulation and DG ltlt0)
• The two C3 species generated in next step are
  energetically equivalent because both halves of
  the fructose are phophorylated.

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Aldolase reaction

• Reverse Aldol results in C-C bond cleavage
  between Ca and Cb (relative to carbonyl)
• Logic
• Cleavage of C6 species to simpler compounds under
  physiological conditions.
• Products are easily interconverted thus, all
  subsequent enzymatic steps are common to both C3
  fragments.

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Triose phosphate isomerase reaction

• 1,2 carbonyl shift via enediolate intermediate
• Logic
• Metabolic economy interconversion of GAP and
  DHAP allows both C3 fragments of glucose to be
  utilized by a single set of enzymes
• Stereoelectronic control by TIM prevents
  formation of toxic methyl glyoxal

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Glycolytic pathway. First half energy
consuming glucose ? DHAP GAP Second half
energy producing 2GAP ? 2 pyruvate
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GAPDH reaction

• Oxidation of CHO to -COOH with phosphoryl
  transfer to yield a high energy mixed anhydride
• Logic
• The major step in energy extraction
• Sets up a substrate-level phosphorylation and
  generates NADH (even more ATP from e- transport
  and oxidative phos.)

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Table 16.3
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Phospoglycerate kinase reaction
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Phospoglycerate mutase reaction

• 1,2-Phosphoryl shift
• Logic
• Sets up the synthesis of pyruvate (i.e., an
  a-keto acid- important for TPP reactions)

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detour to make 2,3-BPG
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What explains these curves?
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Enolase reaction

• Elimination of water CC bond formation
• Logic
• Formation of a high-energy compound for substrate
  level phosphorylation

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Pyruvate kinase reaction

• Substrate-level phosphorylation
• Logic
• This is the pay off. The reaction generates
  ATP in excess of initial investment

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Lactate dehydrogenase (LDH)
NADH, H
NAD
lactate
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The two steps of Alcoholic Fermenation
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alcohol dehydrogenase (ADH)
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TCA cycle ox. phosphorylation
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T state (inactive) R state (active)
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F-2,6-BP is the most potent allosteric activator
of PFK ATP is an inactivator of PFK