Thiamine (TPP) decarboxylation template

The C2 carbanion (ylide) of thiamine pyrophosphate adds to the ketone of pyruvate; the adduct loses CO₂ with the thiazolium ring as electron sink (enamine), which is protonated to hydroxyethyl-TPP and releases acetaldehyde, regenerating the ylide.

Mechanism step by step

Pyruvate decarboxylase: the thiazolium ylide adds to C=O, CO₂ leaves to an enamine, and acetaldehyde is released

1. Ylide adds to C=O – C2⁻ of the thiazolium attacks the ketone; an enzyme acid (BH⁺) protonates the O
2. Decarboxylation – CO₂ leaves; the thiazolium N⁺ takes the electrons (enamine)
3. Protonation – The enamine carbon takes H⁺: hydroxyethyl-TPP
4. Release – B removes the OH proton; acetaldehyde leaves and the ylide is regenerated

Key points

• C2–H of the thiazolium ring is unusually acidic because the carbanion (ylide) is stabilised by the adjacent N⁺ and S (Breslow).
• TPP acts as an electron sink: the positively charged ring holds the electrons left by CO₂ as an enamine (an "acyl-anion equivalent").
• R1 is the aminopyrimidine (its 4′-imino group helps deprotonate C2); R2 carries the diphosphate that binds Mg²⁺.
• The same hydroxyethyl-TPP forms in pyruvate dehydrogenase and transketolase; thiamine deficiency causes beriberi and Wernicke–Korsakoff syndrome.

Drawn with 146 atoms, 17 arrows, 8 shapes – every one editable in MolDraw.

Sources

• Nelson & Cox, Lehninger Principles of Biochemistry, 8th ed., 2021, ch. 14 Textbook
• Berg, Tymoczko, Gatto & Stryer, Biochemistry, 9th ed., 2019, ch. 16 Textbook
• Breslow, Ann. N. Y. Acad. Sci. 1962, 98, 445 Original paper