Learning Objectives for this Section


taking the pyruvates from glycolysis (and other pathways), by way of the transition reaction mentioned above, and completely breaking them down into CO2 molecules, H2O molecules, and generating additional ATPs by oxidative phosphorylation (def).

In prokaryotic cells (see Fig. 15), the citric acid cycle occurs in the cytoplasm; in eukaryotic cells (see Fig. 16) the citric acid cycle takes place in the matrix of the mitochondria.

The overall reaction for the citric acid cycle is:

2 acetyl groups + 6 NAD+ + 2 FAD + 2 ADP + 2 Pi

yields 4 CO2 + 6 NADH + 6 H+ + 2 FADH2 + 2 ATP

The citric acid cycle (see Fig. 17) provides a series of intermediate compounds that donate protons and electrons to the electron transport chain by way of the reduced coenzymes NADH and FADH2. The electron transport chain then generates additional ATPs by oxidative phosphorylation (def). The citric acid cycle also produces 2 ATP by substrate phosphorylation (def).

In addition to their roles in generating ATP, the citric acid cycle also plays an important role in the flow of carbon through the cell by supplying precursor metabolites (def) for various biosynthetic pathways (see Fig. 3).

The citric acid cycle involves 8 distinct steps, each catalyzed by a unique enzyme. You are not responsible for knowing the chemical structures or enzymes involved in the steps below. They are included to help illustrate how the molecules in the pathway are manipulated by the enzymes in order to to acheive the required products.

1. The citric acid cycle begins when Coenzyme A transfers its 2-carbon acetyl group to the 4-carbon compound oxaloacetate to form the 6-carbon molecule citrate (see Fig. 18).

2. The citrate is rearranged to form an isomeric form (def), isocitrate (see Fig. 19).

3. The 6-carbon isocitrate is oxidized and a molecule of carbon dioxide is removed producing the 5-carbon molecule alpha-ketoglutarate. During this oxidation, NAD+ is reduced to NADH + H+ (see Fig. 20).

4. Alpha-ketoglutarate is oxidized, carbon dioxide is removed, and coenzyme A is added to form the 4-carbon compound succinyl-CoA. During this oxidation, NAD+ is reduced to NADH + H+ (see Fig. 21).

5. CoA is removed from succinyl-CoA to produce succinate. The energy released is used to make guanosine triphosphate (GTP) from guanosine diphosphate (GDP) and Pi by substrate-level phosphorylation (def). GTP can then be used to make ATP (see Fig. 22).

6. Succinate is oxidized to fumarate. During this oxidation, FAD is reduced to FADH2 (see Fig. 23).

7. Water is added to fumarate to form malate (see Fig. 24).

8. Malate is oxidized to produce oxaloacetate, the starting compound of the citric acid cycle. During this oxidation, NAD+ is reduced to NADH + H+ (see Fig. 25).

The NADH + H+ and FADH2 carry protons and electrons to the electron transport chain to generate additional ATP by oxidative phosphorylation (def).


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Updated: June 26, 2001