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18.3C: Citric Acid (Krebs) Cycle

Skills to Develop

  • State two other names for the citric acid cycle.
  • Briefly describethe function of the citric acid cycle during aerobic respiration and indicate the reactants and products.
  • Compare where the citric acid cycle occurs in prokaryotic cells and in eukaryotic cells.
  • State the total number of ATP produced by substrate-level phosphorylation for each acetyl-CoA that enters the citric acid cycle.
  • State the total number of NADH and FADH2 produced for each acetyl-CoA that enters the citric acid cycle.
  • During aerobic respiration, state what happens to the NADH and the FADH2 produced during the citric acid cycle.

The citric acid cycle, also known as the tricarboxylic acid cycle and the Krebs cycle, completes the oxidation of glucose by taking the pyruvates from glycolysis (and other pathways), by way of the transition reaction mentioned previously, and completely breaking them down into \(CO_2\) molecules, \(H_2O\) molecules, and generating additional ATP by oxidative phosphorylation. In prokaryotic cells, the citric acid cycle occurs in the cytoplasm; in eukaryotic cells the citric acid cycle takes place in the matrix of the mitochondria.

The overall reaction for the citric acid cycle is:

\[\text{2 acetyl groups} + 6 NAD^+ + 2 FAD + 2 ADP + 2 P_i\]

\[ \rightarrow 4 CO_2 + 6 NADH + 6 H^+ + 2 FADH_2 + 2 ATP\]

The citric acid cycle (Figure Figure \(\PageIndex{1}\)) provides a series of intermediate compounds that donate protons and electrons to the electron transport chain by way of the reduced coenzymes \(NADH\) and \(FADH_2\). The electron transport chain then generates additional ATPs by oxidative phosphorylation. The citric acid cycle also produces 2 ATP by substrate phosphorylation and plays an important role in the flow of carbon through the cell by supplying precursor metabolites for various biosynthetic pathways.

Figure \(\PageIndex{1}\): The Citric Acid Cycle (also Known as the Tricarboxylic Acid Cycle and the Krebs Cycle). The two molecules of acetyl-CoA from the transition reaction enter the citric acid cycle. This results in the formation of 6 molecules of \(NADH\), two molecules of \(FADH_2\), two molecules of ATP, and four molecules of \(CO_2\). The NADH and FADH2 molecules then carry electrons to the electron transport system for further production of ATPs by oxidative phosphorylation.

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 achieve the required products.

Step 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 (Figure Figure \(\PageIndex{2}\)).

The Citric Acid Cycle, Step 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.

Figure \(\PageIndex{2}\): The Citric Acid Cycle, Step 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.

Step 2: The citrate is rearranged to form an isomeric form, isocitrate (Figure \(\PageIndex{3}\)).

The Citric Acid Cycle, Step 2. The citrate is rearranged to form an isomeric form, isocitrate.

Figure \(\PageIndex{3}\): The Citric Acid Cycle, Step 2. The citrate is rearranged to form an isomeric form, isocitrate.

Step 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 \(NADH\) and \(H^+\) (Figure \(\PageIndex{4}\)).

The Citric Acid Cycle, Step 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+.

Figure \(\PageIndex{4}\): The Citric Acid Cycle, Step 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+.

Step 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+ (Figure \(\PageIndex{5}\)).

The Citric Acid Cycle, Step 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+.

Figure \(\PageIndex{5}\): The Citric Acid Cycle, Step 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+.

Step 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. GTP can then be used to make ATP (Figure \(\PageIndex{6}\)).

The Citric Acid Cycle, Step 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. GTP can then be used to make ATP.

Figure \(\PageIndex{6}\): The Citric Acid Cycle, Step 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. GTP can then be used to make ATP.

Step 6: Succinate is oxidized to fumarate. During this oxidation, \(FAD\) is reduced to \(FADH_2\) (Figure \(\PageIndex{7}\)).

The Citric Acid Cycle, Step 6. Succinate is oxidized to fumarate. During this oxidation, FAD is reduced to FADH2.

Figure \(\PageIndex{7}\): The Citric Acid Cycle, Step 6. Succinate is oxidized to fumarate. During this oxidation, FAD is reduced to FADH2.

Step 7: Water is added to fumarate to form malate (Figure \(\PageIndex{8}\)).

The Citric Acid Cycle, Step 7. Water is added to fumarate to form malate.

Figure \(\PageIndex{8}\): The Citric Acid Cycle, Step 7. Water is added to fumarate to form malate.

Step 8: Malate is oxidized to produce oxaloacetate, the starting compound of the citric acid cycle. During this oxidation, NAD+ is reduced to NADH + H+ (Figure \(\PageIndex{9}\)).

The Citric Acid Cycle, Step 8. Malate is oxidized to produce oxaloacetate, the starting compound of the citric acid cycle. During this oxidation, NAD+ is reduced to NADH + H+.

Figure \(\PageIndex{9}\): The Citric Acid Cycle, Step 8. Malate is oxidized to produce oxaloacetate, the starting compound of the citric acid cycle. During this oxidation, NAD+ is reduced to NADH + H+.

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

Summary

  1. Aerobic respiration involves four stages: glycolysis, a transition reaction that forms acetyl coenzyme A, the citric acid (Krebs) cycle, and an electron transport chain and chemiosmosis.
  2. The citric acid cycle, also known as the tricarboxylic acid cycle and the Krebs cycle, completes the oxidation of glucose by taking the pyruvates from glycolysis, by way of the transition reaction, and completely breaking them down into CO2 molecules, H2O molecules, and generating additional ATP by oxidative phosphorylation.
  3. The citric acid cycle 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. The citric acid cycle also produces 2 ATP by substrate phosphorylation.
  4. The overall reaction for the citric acid cycle is:\[ 2 acetyl groups + 6 NAD^+ + 2 FAD + 2 ADP + 2 P_i yields 4 CO_2 + 6 NADH + 6 H^+ + 2 FADH_2 + 2 ATP.\]
  5. The citric acid cycle also plays an important role in the flow of carbon through the cell by supplying precursor metabolites for various biosynthetic pathways.

Contributors

  • Dr. Gary Kaiser (COMMUNITY COLLEGE OF BALTIMORE COUNTY, CATONSVILLE CAMPUS)