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IV. THE KREBS CYCLE

  1. The fate of pyruvic acid depends upon the presence of absence of oxygen. If oxygen is present, pyruvic acid enters the mitochondrion where it is completely oxidized by a series of enzyme-controlled reactions.
  2. Formation of Acetyl CoA: Linking Glycolysis to the Krebs Cycle
    1. The junction between glycolysis and the Krebs Cycle is the oxidation of pyruvic acid to acetyl CoA
      1. Pyruvic acid molecules move from the cytosol into the mitochondrion.
      2. This step is catalyzed by a multienzyme complex which:
        1. Removes carbon dioxide from the carboxyl group of pyruvic acid, changing it from a three-carbon to a two-carbon compound.
        2. Oxidizes the two-carbon fragment to acetic acid, while reducing NAD+ to NADH with the extracted electrons.
        3. Attaches coenzyme A with an unstable bond to the acetyl group, forming acetyl CoA.
      3. Since glycolysis produced two pyruvic acid molecules per glucose, there are two NADH molecules produced as pyruvic acid is oxidized to acetyl-CoA.
  3. How the Krebs Cycle Works
    1. The Krebs Cycle reactions oxidize the remaining acetyl fragments of carbon dioxide.
    2. Energy released from this exergonic process is used to reduce coenzyme (NAD+ and FAD) and to phosphorylate ATP (substrate-level phosphorylation).
    3. Cycle named either the citric acid cycle for the first main product of the cycle or the Krebs cycle in honor of Sir Hans Krebs.
    4. The Krebs cycle has eight enzyme-controlled steps which occur in the mitochondrial matrix.
  4. There are ten steps of the Krebs Cycle: You need to refer to (Figure 9.11) on page 169 of Campbell. Remember, you do not have to memorize the details of the reaction. I am interested in your knowledge of the main features of the cycle.
    1. STEP 1: The unstable bond of acetyl CoA breaks, and the two-carbon acetyl group bonds to the four-carbon oxaloacetic acid to form six-carbon citric acid.
    2. STEP 2: Citric acid is isomerized to isocitric acid.
    3. STEP 3: Two major events occur during this step:
      1. Isocitric acid loses carbon dioxide leaving a five-carbon molecule.
      2. The five-carbon compound is oxidized and NAD+ is reduced.
    4. STEP 4: A multienzyme complex catalyzes:
      1. Removal of carbon dioxide.
      2. Oxidation of the remaining four-carbon compound and reduction of NAD+.
      3. Attachment of CoA with a high energy bond to form succinyl CoA.
    5. STEP 5: Substrate-level phosphorylation occurs in a series of enzyme catalyzed reactions:
      1. The high energy bond is succinyl-CoA breaks, and some energy is conserved as CoA is displaced by a phosphate group.
      2. The phosphate group is transferred to GDP to form GTP and succinic acid.
      3. GTP donates a phosphate group to ADP to form ATP.
    6. STEP 6: Succinic acid is oxidized to fumaric acid and FAD is reduced.
      1. Two hydrogens are transferred to FAD to form FADH2.
      2. FADH2 stores less energy than NADH.
      3. The dehydrogenase that catalyzes this reaction is bound to the inner mitochondrial membrane.
    7. STEP 7: Water is added to fumaric acid which rearranges its chemical bonds to form malic acid.
    8. STEP 8: Malic acid is oxidized and NAD is reduced.
      1. A molecule of NADH is produced.
      2. Oxaloacetic acid is regenerated to begin the cycle again.
  5. Summary of the Krebs Cycle (Use Campbell's Figure 9.12, page 170, as your main review for this cycle.)
    1. For every turn of Krebs Cycle:
      1. Two carbons enter in the acetyl fragment of Acetyl CoA.
      2. Two different carbons leave as carbon dioxide.
      3. Coenzymes are reduced; three NADH and one FADH2 are produced.
      4. One ATP molecule is produced by substrate level phosphorylation.
      5. Oxaloacetic acid is regenerated.
    2. For every glucose molecule split during glycolysis, two acetyl fragments are produced. Thus, it takes two turns of the cycle to complete the oxidation of glucose.
    3. Reduced coenzymes produced by the Krebs Cycle (6 NADH and 2 FADH2 per glucose) carry high energy electrons to the electron transport chain where ATP is produced by chemiosmosis. Most of the ATP output of respiration results from this oxidative phosphorylation.
 
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