The transition reaction connects glycolysis to the citric acid (Krebs) cycle. Through a process called oxidative decarboxylation, the transition reaction converts the two molecules of the 3-carbon pyruvate from glycolysis (and other pathways) into two molecules of the 2-carbon molecule acetyl Coenzyme A (acetyl-CoA) and 2 molecules of carbon dioxide. First, a carboxyl group of each pyruvate is removed as carbon dioxide and then the remaining acetyl group combines with coenzyme A (CoA) to form acetyl-CoA. As the two pyruvates undergo oxidative decarboxylation, two molecules of NAD⁺ become reduced to 2NADH + 2H⁺ (see Fig. 13 and Fig. 14). The 2NADH + 2H⁺ carry protons and electrons to the electron transport chain to generate additional ATP by oxidative phosphorylation (def).

The overall reaction for the transition reaction is:

2 pyruvate + 2 NAD⁺ + 2 coenzyme A

yields 2 acetyl-CoA + 2 NADH + 2 H⁺ + 2 CO²

In prokaryotic cells (see Fig. 15), the transition step occurs in the cytoplasm; in eukaryotic cells the pyruvates must first enter the mitochondria (see Fig. 16) because the transition reaction and the citric acid cycle take place in the matrix of the mitochondria.

The two molecules of acetyl-CoA can now enter the citric acid cycle. Acetyl-CoA is also a precursor metabolite (def) for fatty acid synthesis, as shown in Fig. 3.

McGraw-Hill Flash animation illustrating the transition reaction and the Kreb's cycle