D. Cellular Respiration
1. Aerobic Respiration
c. The Citric Acid (Krebs) Cycle
Aerobic respiration (def) is the aerobic catabolism of nutrients to carbon dioxide, water, and energy, and involves an electron transport system (def) in which molecular oxygen is the final electron acceptor. Most eukaryotes and prokaryotes use aerobic respiration to obtain energy from glucose. The overall reaction is:
C6H12O6 + 6O2 yields 6CO2 + 6H2O + energy (as ATP)
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. We will now look at the citric acid (Krebs) Cycle.
The Citric Acid (Krebs) 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 above, and completely breaking them down into CO2 molecules, H2O molecules, and generating additional ATP by oxidative phosphorylation (def).
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. 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 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.
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. 2).
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. 4).
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. 5).
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. 6).
6. Succinate is oxidized to fumarate. During this oxidation, FAD is reduced to FADH2 (see Fig. 7).
7. Water is added to fumarate to form malate (see Fig. 8).
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. 9).
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