Overview

• Cellular respiration is the process by which the pyruvate produced by glycolysis is further oxidized to H2O and CO2.
• Stage one of cellular respiration is oxidation of fuels to acetyl CoA. It generates ATP, NADH, and FADH2.
• Stage two of cellular respiration is the oxidation of acetyl groups to CO2 in the citric acid cycle (tricarboxylic acid cycle, TCA, and Krebs cycle)

  • Nearly universal pathway
  • Generates NADH, FADH2, and one GTP
• Stage three of cellular respiration is the electron transport chain and oxidative phosphorylation.

  • Generates the vast majority of ATP from catabolism
• Pyruvate is the metabolite that links two central catabolic pathways, glycolysis and the citric acid cycle. It is therefore a logical point for regulation that determines the rate of catabolic activity and the partitioning of pyruvate among its possible uses.
• The reactions of the citric acid cycle follow a chemical logic. In its catabolic role, the citric acid cycle oxidizes acetyl CoA to CO2 and H2O. Energy from the oxidations in the cycle drives the synthesis of ATP.
• The chemical strategies for activating groups for oxidation and for conserving energy in the form of reducing power and high energy compounds are used in many other biochemical pathways.
• The citric acid cycle is a hub of metabolism, with catabolic pathways leading in and anabolic pathways leading out.
• Acetate groups (acetyl-CoA) from the catabolism of various fuels are used in the synthesis of metabolites like amino acids, fatty acids, and sterols.
• The breakdown products of many amino acids and nucleotides are intermediates of the cycle, and they can be fed in or siphoned off as needed by the cell.
• The central role of the citric acid cycle in metabolism requires that it be regulated in coordination with many other pathways. Regulation occurs by both allosteric and covalent mechanisms that overlap and interact to achieve homeostasis.
• Some mutations that affect the reactions of the citric acid cycle lead to tumor formation.
• Enzymes have evolved to form complexes to efficiently achieve a series of chemical transformations without releasing the intermediates into bulk solvent. This strategy, seen in the pyruvate dehydrogenase complex and the metabolons of the citric acid cycle, is ubiquitous in other pathways of metabolism, in respiration, and in many "-somes" that assembles and disassemble informational macromolecules.