Coenzyme A (CoA) is a complex molecule consisting of mercaptamine, β-alanine, pantoic acid, diphosphate, pentose, phosphate and adenine moieties:

Structure of coenzyme A by NEUROtiker — adapted from https://en.wikipedia.org/wiki/Coenzyme_A#/media/File:Coenzym_A.svg

Which part of it actually plays role in the formation of proton and formate from pyruvate ion, and what is the mechanism? I know that the mercaptamine part has the SH group (thiol group) and there are many acidic H atoms in the molecule.

Plus, how does the lyase catalyst play its role here? Is it a SN1 or SN2 reaction? Please provide some proper references.

  • 2
    $\begingroup$ I think you will get better information just searching the literature on pyruvate formate lyase enzyme mechanism. $\endgroup$
    – Andrew
    May 17, 2022 at 12:17

1 Answer 1


The reversible conversion of pyruvate ion and coenzyme A (CoA) into $\ce{acetyl-CoA}$ and formate ion (Figure 1) is not a one step reaction but a complex multistep radical reaction (Ref.1), thus it is neither $\mathrm{S_N1}$ nor $\mathrm{S_N2}$:

Conversion of pyruvate to formate

Two research groups (Ref.2 & 3) have proposed two mechanisms both involving radical initiation (Figures are from Ref.1):

Mechanism for the conversion of pyruvate to formate-1

Both mechanisms have taken similar path for the radical assisted chevage. The theoretical studies (Ref. 1) and crystal structure of an intermediate (Ref.4) have confirmed the validity of mechanism(s):

Mechanism for the conversion of pyruvate to formate-2


  1. Fahmi Himo and Leif A. Eriksson, "Catalytic Mechanism of Pyruvate Formate-Lyase (PFL). A Theoretical Study," J. Am. Chem. Soc. 1998, 120(44), 11449–11455 (DOI: https://doi.org/10.1021/ja9820947).
  2. J. Knappe, S. Elbert, M. Frey, and A. F. V. Wagner, "Pyruvate formate-lyase mechanism involving the protein-based glycyl radical," Biochem. Soc. Trans. 1993, 21(3), 731–734 (DOI: https://doi.org/10.1042/bst0210731).
  3. Camran V. Parast, Kenny K. Wong, Sandra A. Lewisch, John W. Kozarich, Jack Peisach, and Richard S. Magliozzo, "Hydrogen Exchange of the Glycyl Radical of Pyruvate Formate-Lyase Is Catalyzed by Cysteine 419," Biochemistry 1995, 34(8), 2393–2399 (DOI: https://doi.org/10.1021/bi00008a001).
  4. Andreas Becker and Wolfgang Kabsch, "X-ray Structure of Pyruvate Formate-Lyase in Complex with Pyruvate and CoA: How the Enzyme Uses the Cys-418 Thiyl Radical for Pyruate Clevage," J. Biol. Chem 2002, 277(42), 40036-40042 (DOI: https://doi.org/10.1074/jbc.M205821200).

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