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The Citric Acid Cycle - Introduction

Notes

The Citric Acid Cycle - Introduction

Now, let's take a closer look at the citric acid cycle.

  • First, draw pyruvate in the cytosol.
  • Draw the layers of the mitochondrial membrane below it.
    • Specifically label the inner mitochondrial membrane and the matrix within it.
  • Show that pyruvate must be actively transported from the cytosol into the mitochondrial matrix.
  • Now, draw acetyl CoA, the first intermediate in the cycle, as a two-carbon acetyl group bound to coenzyme A.
  • Show that pyruvate is converted to acetyl CoA in the matrix.
    • Pyruvate dehydrogenase catalyzes this reaction. We cover it in detail elsewhere.
  • Indicate that acetyl CoA is produced when any of the following molecules are broken down:
    • Carbohydrates, which are first broken down to pyruvate.
    • Fatty acids
    • Amino acids.

We will focus on carbohydrate breakdown, and in particular, glucose breakdown.

  • Indicate that the citric acid cycle is the second step in glucose breakdown.

From here, we will draw the intermediates of the cycle as well as the energy and waste products. Let's start with the intermediates of the citric acid cycle, since we have already drawn the first (acetyl CoA).

  • Next, draw oxaloacetate as a four carbon structure.
  • Use arrows to show that it combines with the two-carbon acetyl group in acetyl CoA to form a third intermediate.
    • Show that Ccoenzyme A leaves at this step.
  • Indicate that the third intermediate is citrate: a six-carbon molecule.
  • Now, fill in the remaining intermediates of our driving circle as follows:
    • Isocitrate: an isomer (iso) of citrate.
    • Alpha-ketoglutarate: a five-carbon molecule
    • Succinyl CoA: a four-carbon molecule bound to coenzyme A
  • Complete the cycle with the remaining four-carbon intermediates:
    • Succinate
    • Fumarate
    • Malate
  • Show that malate is oxidized to oxaloacetate, thus completing the cycle.
  • We can remember these intermediates in the order in which they appear by using an easy mnemonic: Oh, Can I Keep Studying Science For Med-school!

Finally, let's add the energy and waste products of the cycle.

We'll start with the waste: carbon dioxide.

  • Show that carbon dioxide is released whenever an intermediate loses a carbon molecule:
    • 3-carbon pyruvate forms 2-carbon acetyl CoA
    • 6-carbon isocitrate forms 5-carbon alpha-ketoglutarate
    • 5-carbon alpha-ketoglutarate forms 4-carbon succinyl coA
  • The cycle also produces water, but we will not draw this here.

Now, let's add the energy products: NADH, FADH2 and ATP.

  • Show that one NAD+ is reduced to NADH in the same three reactions that release carbon dioxide.
  • Indicate that a final NAD+ is reduced in the oxidation of malate to oxaloacetate.
  • Show that FAD is reduced to FADH2 when succinate is oxidized to fumarate (associate the F in FAD with the F in Fumarate).
  • Show that these reduced carriers then shuttle their high-energy cargo to the inner mitochondrial membrane where oxidative phosphorylation occurs.
  • Finally, illustrate that succinyl CoA loses its coenzyme group via substrate-level phosphorylation, which produces ATP from ADP and phosphate.
  • The citric acid cycle completes the oxidation of glucose via these redox reactions, which reduce NAD+ and FAD.
    • However, this cycle could not continue to turn without the third phase of glucose breakdown: oxidative phosphorylation, which recycles NAD+ and FAD.