Pyruvate shunt

The pyruvate shunt is the transitional step that converts pyruvate (the end product of glycolysis) into acetyl-CoA, CO2, and NADH, effectively bridging glycolysis to the Krebs cycle. This reaction is catalyzed by the pyruvate dehydrogenase complex in the mitochondrial matrix (in eukaryotes) and is sometimes called pyruvate oxidation or the link reaction.

• During this conversion, each pyruvate (3C) loses one carbon as CO2 (decarboxylation), and the remaining 2-carbon acetyl group is attached to coenzyme A to form acetyl-CoA. Meanwhile, NAD+ is reduced to NADH. Since one glucose yields two pyruvate, the reaction occurs twice per glucose (producing 2 acetyl-CoA + 2 NADH + 2 CO2 per glucose).
• This step is irreversible and highly regulated. It requires several B-vitamin-derived cofactors (like thiamine, lipoic acid, NAD+, FAD, CoA). For example, thiamine (vitamin B1) is a cofactor; deficiency can impair pyruvate oxidation and lead to a backup of pyruvate (which gets converted to lactate).
• Oxygen is indirectly required: pyruvate will only be shunted into acetyl-CoA if the cell can eventually send electrons from NADH into the oxygen-requiring electron transport chain. In anaerobic conditions (no O2), pyruvate is more likely to undergo fermentation instead of entering the mitochondria.

• Bridge step: Test questions often ask how pyruvate enters the citric acid cycle. Remember that pyruvate itself cannot enter the Krebs cycle directly; it must first be converted to acetyl-CoA. The enzyme complex that does this (pyruvate dehydrogenase) links glycolysis to the TCA cycle.
• Products and yield: A common question: 'What are the products when one molecule of pyruvate is oxidized-' Answer: acetyl-CoA, NADH, and CO2 (per pyruvate). They might also ask per glucose (which would be twice those amounts). Recognize that no ATP is made directly in this step.
• Location clue: In eukaryotes, this pyruvate-to-acetyl-CoA conversion happens in the mitochondrial matrix. In prokaryotes (which lack mitochondria), it happens in the cytoplasm. A question might give a scenario about where these reactions take place in bacteria vs. humans.