Cysteines thiolate anion from

The final step in the /3-oxidation cycle is the cleavage of the /3-ketoacyI-CoA. This reaction, catalyzed by thiolase (also known as j8-ketothiolase), involves the attack of a cysteine thiolate from the enzyme on the /3-carbonyI carbon, followed by cleavage to give the etiolate of acetyl-CoA and an enzyme-thioester intermediate (Figure 24.17). Subsequent attack by the thiol group of a second CoA and departure of the cysteine thiolate yields a new (shorter) acyl-CoA. If the reaction in Figure 24.17 is read in reverse, it is easy to see that it is a Claisen condensation—an attack of the etiolate anion of acetyl-CoA on a thioester. Despite the formation of a second thioester, this reaction has a very favorable A).q, and it drives the three previous reactions of /3-oxidation. 

Sulfur mustard was shown by Noort et al. (24) to alkylate the cysteine-34 residue in human serum albumin. The site of alkylation was identified in a tryptic digest of albumin from blood exposed to [14C] sulfur mustard. The cysteine-34 residue is the only free cysteine residue in human serum albumin and has a relatively low pKa, caused by intramolecular stabilization of the thiolate anion. It has previously been identified as a nucleophilic site capable of reacting with various electrophiles (25,26). 

Sulphur mustard alkylates the cysteine-34 residue in human serum albumin (Noort et al., 1999, 2004b), which is known to react with a number of electrophiles. This residue is much more accessible than the cysteines in haemoglobin, and its reactivity is promoted by its relatively low pKa, resulting from intramolecular stabilization of the thiolate anion. Aspartic and glutamic acid residues on albumin also react with... 

Alkyl halides are even less reactive than acyl halides, as indicated by the compilation of reaction rates of thiolate anions with various types of alkyl halides (282). Nevertheless, potentially useful affinity labels have been synthesized with alkyl halide substituents and have been shown to specifically inactivate several enzymes, albeit slowly the low reactivity of the alkyl halides may minimize nonspecific reaction. Adenosine 5 -(2-bromoethyl)phosphate has been characterized and reported to inactivate NAD -dependent isocitrate dehydrogenase (283). The 2 - and 3 -(2-bromoethyl)-AMP labels have also been synthesized, and model reactions of the bromoethyl-AMPs with cysteine, lysine, histidine, and tyrosine have been studied (284). More recently, esters of adenosine 5 -monophosphate have been prepared with ethyl, propyl, or hexyl moieties and bromo or chloro substituents at the w position (285). Yeast alcohol dehydrogenase exhibited enhanced inactivation by the hexyl derivative, but inactivation rates of other dehydrogenases were unremarkable. Two iodopropyl derivatives of cAMP have been described, namely, 1, A -(3-iodopropyleno)adenosine 3, 5 -cyclic monophosphate and 3 -0-(2-iodo-3-hydroxypropyl)adenosine 3, 5 -cyclic monophosphate the latter inactivates cAMP phosphodiesterase from human platelets, with a pseudo-first-order rate constant of 0.147 hr" (286). 

Inorganic radicals, formed from the reaction between anions and OH can also oxidize thiols to free thiyl radicals. The spedes (CT S), Bi, Cl and I (formed by radiolysis of NaOsaturated solutions of CNS, Br, a, I ) are reduced by cysteine with rate constants of 0-5-8-5 x 10 1 mol s and the rate constants for (CNSj ), B17 and increase by approximately a factor of 10 when the thiol is converted to the thiolate anion . (Cli exists only in acidic solution.) CO is also reduced rapidly by the thiolate anion of cysteine. ... 

---