Thiol endogenous

Drugs coupled via a disulfide bond like, captopril, are rapidly released from the protein-spacer moiety of the conjugate, enzymatically by 3-lyase and/or non-enzymatically by thiol-disulfide exchange with endogenous thiols [68]. 

Yamamoto, A., Tomoo, K., Doi, M, Ohishi, H., Inoue, M., Ishida, T., Yamamoto, D., Tsuboi, S., Okamoto, H., Okada, Y. (1992). Crystal structure of papain-succinyl-Gbi-Val-Val-Ala-Ala-p-nitroaniUde complex at 1.7-A resolution noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors. Biochemistry 31,11305-11309. 

Reuvers AP, Green stock CL, Borsa J, Chapman JD (1973) Studies on the mechanism of chemical radioprotection by dimethyl sulphoxide. Int J Radiat Biol 24 533-536 Revesz L (1985) The role of endogenous thiols in intrinsic radioprotection. Int J Radiat Biol... 

Animals. Rapidly and completely metabolized, primarily by oxidative dealkylation of the amino groups and by reaction of chlorine atom with endogenous thiols. Diaminochlorotriazine is the main primary metabolite, which readily conjugates with glutathione. More than 50% of the dose is eliminated in the urine and around 33% in feces within 24 hr... 

Knowledge of the interaction of thiols with DNA-derived radicals is much less extensive. Moreover, one function of endogenous thiols is to repair radical damage in nucleic acids. Surprisingly, little was known about the rate constants for the thiol-repair reactions with pyrimidine-derived radicals having well-defined structures (Pyr ) [reaction (2)] ... 

Further examples that some radioprotectors cause an increase of endogenous thiol groups in various tissues have been reported during the past year. Amino thiols, cystamine, serotonin, compounds which lower O2 tension in tissues, and anoxia, bring about an increase in cellular thiol content, which, with the amino thiols, is fold greater than that supplied by... 

Finally, glutathione and other endogenous thiols (including albumin) are able to inactivate free radicals (e.g. R, HO, HOO , ROO ) and have thus a critical role to play in cellular protection (88). The reactions involved are highly complex and incompletely understood the simplest are as follows. 

Mitchell JB, Biaglow JE, Russo A. Role of glutathione and other endogenous thiols in radiation protection. Pharmacol Ther... 

B. Exogenous Nitric Oxide Donors Nitric oxide is released from several important dmgs, including nitroprusside (Chapter 11), nitrates, (Chapter 12), and nitrites. Release from nitro-prusside occurs spontaneously in the blood in the presence of oxygen, while release from nitrates and nitrites is enzymatic, intracellular, and requires the presence of thiol compounds such tis cysteine. Tolerance may develop to nitrates and nitrites if endogenous thiol compounds are depleted. 

Although they are more stable than hydrates, simple geminal dithiols (Nos 1660 and 1661) can undergo hydrolysis to yield their parent aldehydes and to release hydrogen sulfide (Mayer et al., 1963). The metabolism of the other simple aliphatic dithiol (No. 1709) is predicted to involve the pathways described above for simple thiols. Urinary metabolites could result from methylation, S-oxidation of a sulfur atom to yield a polar sulfonate and the formation of mixed disulfides by combination with a low molecular weight endogenous thiol such as cysteine. 

The reduction of xenobiotic disulfides is believed to be extensive and can be catalysed enzymatically by GSH reductase (Waring, 1996) or thioltransferases (Wells et al., 1993), as well as chemically by exchange with GSH, thioredoxin, cysteine or other endogenous thiols. Reduction of non-cyclic disulfides results in the formation of thiols of low molecular weight that are metabolized via the various pathways described above for simple thiols. 

The presence of endogenous thiol proteinase inhibitors in mammalian tissues has been reported by many investigators (26-29) but these have not purified or well characterized. Kominami et al. (30, 31) recently purified a thiol proteinase inhibitor from rat liver. This article reviews the properties, structures, and functions of thiol endopep-tidases in mammalian lysosomes and the characteristics of the endogenous inhibitor. 

Table 5.3 Published papers on the measurement of endogenous thiols/disulfides by HPLC-ED...

Captopril, an angiotensin-converting enzyme inhibitor, at high doses depleted endogenous thiols... 

The importance of endogenous thiols In the development of natural radioresistance is shown by the close correlation between the radioresistance of mice and the concentration of thiol In their blood-forming tissues of spleen homogenates. The great radioresistance of M. radlodurans Is attributed to an abundant and expendable thiol component that protects the cell... 

---