8.4: Transition Reaction and Krebs Cycle

Learning Objectives

• Describe why glycolysis is not oxygen dependent
• Define and describe the net yield of three-carbon molecules, ATP, and NADH from glycolysis
• Explain how three-carbon pyruvate molecules are converted into two-carbon acetyl groups that can be funneled into the Krebs cycle.
• Define and describe the net yield of CO₂, GTP/ATP, FADH₂, and NADH from the Krebs cycle
• Explain how intermediate carbon molecules of the Krebs cycle can be used in a cell

Transition Reaction, Coenzyme A, and the Krebs Cycle

Glycolysis produces pyruvate, which can be further oxidized to capture more energy. For pyruvate to enter the next oxidative pathway, it must first be decarboxylated by the enzyme complex pyruvate dehydrogenase to a two-carbon acetyl group in the transition reaction, also called the bridge reaction (see Appendix C and Figure \(\PageIndex{3}\)). In the transition reaction, electrons are also transferred to NAD⁺ to form NADH. To proceed to the next phase of this metabolic process, the comparatively tiny two-carbon acetyl must be attached to a very large carrier compound called coenzyme A (CoA). The transition reaction occurs in the mitochondrial matrix of eukaryotes; in prokaryotes, it occurs in the cytoplasm because prokaryotes lack membrane-enclosed organelles.

Figure \(\PageIndex{3}\): (a) Coenzyme A is shown here without an attached acetyl group. (b) Coenzyme A is shown here with an attached acetyl group.

Query \(\PageIndex{1}\)

 

The Krebs cycle transfers remaining electrons from the acetyl group produced during the transition reaction to electron carrier molecules, thus reducing them. The Krebs cycle also occurs in the cytoplasm of prokaryotes along with glycolysis and the transition reaction, but it takes place in the mitochondrial matrix of eukaryotic cells where the transition reaction also occurs. The Krebs cycle is named after its discoverer, British scientist Hans Adolf Krebs (1900–1981) and is also called the citric acid cycle, or the tricarboxylic acid cycle (TCA) because citric acid has three carboxyl groups in its structure. Unlike glycolysis, the Krebs cycle is a closed loop: The last part of the pathway regenerates the compound used in the first step (Figure \(\PageIndex{4}\)). The eight steps of the cycle are a series of chemical reactions that capture the two-carbon acetyl group (the CoA carrier does not enter the Krebs cycle) from the transition reaction, which is added to a four-carbon intermediate in the Krebs cycle, producing the six-carbon intermediate citric acid (giving the alternate name for this cycle). As one turn of the cycle returns to the starting point of the four-carbon intermediate, the cycle produces two CO₂ molecules, one ATP molecule (or an equivalent, such as guanosine triphosphate [GTP]) produced by substrate-level phosphorylation, and three molecules of NADH and one of FADH₂. (A discussion and detailed illustration of the full Krebs cycle appear in Appendix C.)

Although many organisms use the Krebs cycle as described as part of glucose metabolism, several of the intermediate compounds in the Krebs cycle can be used in synthesizing a wide variety of important cellular molecules, including amino acids, chlorophylls, fatty acids, and nucleotides; therefore, the cycle is both anabolic and catabolic (Figure \(\PageIndex{5}\)).

Figure \(\PageIndex{4}\): The Krebs cycle, also known as the citric acid cycle, is summarized here. Note incoming two-carbon acetyl results in the main outputs per turn of two CO₂, three NADH, one FADH₂, and one ATP (or GTP) molecules made by substrate-level phosphorylation. Two turns of the Krebs cycle are required to process all of the carbon from one glucose molecule.

Figure \(\PageIndex{5}\): Many organisms use intermediates from the Krebs cycle, such as amino acids, fatty acids, and nucleotides, as building blocks for biosynthesis.

Query \(\PageIndex{1}\)

 

Key Concepts and Summary

• After glycolysis, a three-carbon pyruvate is decarboxylated to form a two-carbon acetyl group, coupled with the formation of NADH. The acetyl group is attached to a large carrier compound called coenzyme A.
• After the transition step, coenzyme A transports the two-carbon acetyl to the Krebs cycle, where the two carbons enter the cycle. Per turn of the cycle, one acetyl group derived from glycolysis is further oxidized, producing three NADH molecules, one FADH₂, and one ATP by substrate-level phosphorylation, and releasing two CO₂ molecules.
• The Krebs cycle may be used for other purposes. Many of the intermediates are used to synthesize important cellular molecules, including amino acids, chlorophylls, fatty acids, and nucleotides.