How does coenzyme A produce proton from pyruvate ions?

[Coenzyme A (CoA)](https://en.wikipedia.org/wiki/Coenzyme_A) 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](https://i.stack.imgur.com/Wh70Z.png)](https://i.stack.imgur.com/Wh70Z.png)


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.




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](https://i.stack.imgur.com/NhuJC.png)](https://i.stack.imgur.com/NhuJC.png)


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](https://i.stack.imgur.com/ArOef.jpg)](https://i.stack.imgur.com/ArOef.jpg)


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](https://i.stack.imgur.com/eBzvI.png)](https://i.stack.imgur.com/eBzvI.png)




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**References:**


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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