Subject glutathione synthesis

Analogs were prepared through total chemical synthesis in which the unstable epoxide was replaced with a cyclopropyl group (4). This afforded compounds that were not subject to epoxide metabolizing enzymes, epoxide hydrolase, and glutathione transferase. We called these compounds PBT (PaceBioAcTive compounds). The PBT competed with the native compounds in binding to neutrophil... 

One of the major points of interest in the chemistry of glutathione has been the chemistry of the mercaptan group. More recently, there has been an additional interest developed in the possibility of glutathione being a common intermediate in the synthesis of all peptide links, particularly in view of the existence of enzyme systems which transfer this 7-glutamyl residue to a whole variety of other amino acids. However, this is not the part of the subject to which I will be addressed. We will limit ourselves, then, to a discussion of sulfur chemistry. 

In an adequately supplied adult male human subject, the total body selenium content is on the order of 30-60 mg, of which one-third is found in the skeleton and two-thirds in the soft tissues. A substantial fraction of kidney selenium is retained even when selenium at other sites is severely depleted during deficiency, and renal selenium is more constant between human populations than selenium in other tissues or body fluids. Regulation of selenoprotein synthesis at the transcription level appears to ensure a hierarchy of preservation of individual selenoproteins at critical sites. The cytosolic glutathione peroxidase (GPx I) and selenoprotein P can donate selenium to other sites whenever overall depletion occurs. Selenium crosses the placenta readily, and breast milk selenium concentration is responsive to changes in maternal selenium intake. In the United States, breast milk Se concentrations are generally in the range of 0.19-0.25 pmol/1, but colostrum has levels that are two or three times higher than those of mature breast milk. 

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