Thioesters as intermediates

The reaction of an amino group with an aldehyde or ketone leads to an imine, which, as we have just seen with aldolase, provides a splendid example of how to bond a carbonyl substrate to an enzyme, and yet maintain its chemical reactivity in terms of enolate anion chemistry. Another type of covalent interaction is quite commonly encountered, and this exploits the thiol group of cysteine. Thiols are more acidic than 

We shall meet several examples of this type of process (see Sections 15.2, 15.4 and 15.5), and so only the general mechanism will be considered at this stage. 

We have shown the cysteine thiol group as uncharged. The pAfa for this group in cysteine is about 10.3, and application of the Henderson-Hasselbach equation (see Section 4.9) indicates there will be negligible ionization at pH 7. Nevertheless, under the influence of a suitable basic group, e.g. arginine pATa 12.5, ionization to thiolate may be possible. In such an environment, thiolate may act as the nucleophile in the mechanism. 

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