Thiol transferase

Several additional points should be made. First, although oxygen esters usually have lower group-transfer potentials than thiol esters, the O—acyl bonds in acylcarnitines have high group-transfer potentials, and the transesterification reactions mediated by the acyl transferases have equilibrium constants close to 1. Second, note that eukaryotic cells maintain separate pools of CoA in the mitochondria and in the cytosol. The cytosolic pool is utilized principally in fatty acid biosynthesis (Chapter 25), and the mitochondrial pool is important in the oxidation of fatty acids and pyruvate, as well as some amino acids. 

Fung and colleagues examined the metabolic conversion of organic nitrates in sub-cellular fractions of bovine coronary artery smooth muscle cells [66, 67]. They found NO-generating capacity to be present in membrane fractions and, with the use of marker enzymes, identified plasma membrane as the primary location. The enzyme involved in bioconversion was not glutathione-S-transferase [68] and differed from those that catalyse activation of organic nitrites [69]. Partial purification [70] established that the molecular sizes of the native enzyme and subunits were approximately 200 kDa and 58 kDa respectively, and that enzymic activity depends on the presence of a free thiol group. 

As mentioned earlier, the therapeutic use of organic nitrites [4] actually predates that of organic nitrates [1], Clinical utilisation of nitrites has, however, been very much less and this is reflected in the relatively sparse attention given to their mechanisms of action. Alkyl nitrites react readily with thiols to form S-nitrosothiols [122], which show biological effects similar to those of NO [11]. Nevertheless, glutathione-S-transferase has been implicated in the metabolism of organic nitrites, via intermediate... 

The number of drugs susceptible to S-methylation is still limited but greater than the number turned over by COMT. Thiopurine methyl transferase (TPMT) is an important enzyme responsible for detoxifying mercaptopurine—a drug used to treat leukemia— as well as azathioprine —a prodrug that is metabolized to mercaptopurine (Fig. 7.12). This enzyme is polymorphic and patients who are homozygous for the deficient enzyme experience severe toxicity when given usual doses of mercaptopurine (19). Similar aromatic and heterocyclic sulfhydryls can also be substrates for TPMT. The similar thiol... 

Thiol conjugation Epoxides Glutathione S-transferases (glutathione or N-acetylcysteine) Glutathione or N-acetyl cysteine thioethers... 

Schistosoma japonica glutathione-S -transferase [24] Conjugate addition of thiols to enones -300 HPLC... 

Evidence was also provided that Insoluble residues may be produced from GSH conjugates via cysteine conjugate or thiol Intermediates. These studies also suggested that certain reactions should be studied in greater detail to assess their importance in pesticide metabolism l.e., the C-S lyase reaction, the methyl transferase reaction, and the transamination reaction. 

Possible biochemical mechanisms of resistance to alkylating agents include changes in ceU DNA repair capability, increases in cell thiol content (which in turn can serve as alternative and benign targets of alkylation), decreases in ceU permeability, and increased activity of glutathione transferases. Increased metaUothionein content has been associated with tumor cell resistance to cisplatin. 

Sulfur nucleophiles such as thiolate anion generally appear near the top of the nucleophi-licity scale and thus readily attack oxepins (Scheme 20). While adduct formation between oxepin (7) and thiols occurs spontaneously upon mixing (74JA6929), a similar reaction between the naturally occurring tripeptide thiol, glutathione, and oxepin-arene oxide intermediates formed during mammalian metabolism is catalyzed by a glutathione epoxide transferase. 

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