Twoelectron reactions

The conversion of two thiols into a disulphide can formally be regarded as a two-electron process:

Two-elect roil oxidation (formal): RS" => RS+ + 2 e"

One-electron oxidation (formal): RS'+ RS* => RSSR

However, the two-electron oxidation of the thiolate ion, RS", to the sulphe-nium ion, is apparently not known, nor is the sulphenium ion a known intermediate.

Known two-electron processes occur e.g. in the displacement reaction of thiols with molecular iodine and in the addition reaction of thiols with double bonds.

Two-electron oxidation by:

2. nucleophilic addition: RS" + YCO-N=N-COY => YCO-N(RS)-NH-COY

The resulting iodide, RSI, of the displacement reaction can further react with a second thiolate anion to give the disulphide in a one-electron oxidation-reduction:

One-electron oxidation-reduction by displacement: RS" + RSI => RSSR + I"

Thus the formation of GSSG from GSH can occur via radical and non-radical mechanisms.

Nucleophilic reactions

The thiol group of GSH reacts as a nucleophil with electrophiles such as conjugated carbonyls. In these highly reactive electrophiles both the C=C double bond may react according to the equation (Figure 1, reaction 7):

or the carbonyl group as well. These reactions are important detoxification mechanisms of toxic products produced by plants or xenobiotics. Furthermore, they reflect the ability of conjugated carbonyls to inactivate low-molecular weight and protein thiols in biological systems. The equilibrium constants as well as the rate constants for forward and reverse reaction are extremely dependent on the carbonyl structure, e.g. the mother compound acrolein reacts more rapidly than any other carbonyl to give very stable ad-ducts (half-lives for reverse reaction 4.6 days). 4-Hydroxy-2-alkenals, which derive from polyunsaturated fatty acids, are somewhat less reactive forming also very stable adducts showing half-lives between 3.4 and 19 days. Thus, the biological activity of aldehydic lipid peroxidation products is primarily determined by the reactivity of conjugated carbonyls towards thiol groups and due to the stability of the adducts (Esterbauer et al. 1975).

In neutral solutions glutathione reacts spontaneously with 4-hydroxyalkenals, e.g. 4-hydroxy-nonenal, to a saturated aldehyde with the glutathione residue bound by a thio-ether linkage at carbon atom 3, but the principal end product (95 %) in aqueous solution is a five-membered cyclic hemi-acetal, which results from an intramolecular rearrangement of the initial product (Esterbauer et al. 1991).


Figure 2. Reaction of glutathione with 4-hydroxyatkenals modified according to Esterbauer et al. 1991.


Figure 2. Reaction of glutathione with 4-hydroxyatkenals modified according to Esterbauer et al. 1991.

Plant products as inducers of glutathione ^-transferases

Glutathione ^-transferases, which occur in plants, several vertebrate species, invertebrates, and microorganisms, are an important group of detoxification enzymes, which catalyse conjugation reactions between GSH and a variety of electrophilic compounds, including many environmental toxins (Lau et al. 1980).

Among the toxins detoxified by glutathione ^-transferases are several carcinogens. Most chemical carcinogens require activation to reactive elec-trophilic forms by phase I enzymes (cytochromes P-450) in order to exert their toxic and neoplastic effects. The resultant electrophiles are susceptible to metabolic conjugation and other types of detoxifications by phase II enzymes, which include glutathione transferases, NAD(P)H:quinone reductase, and UDP-glucuronosyl-transferases. The balance between phaseI and phaseII enzymes is an important determinant of whether exposure to carcinogens will result in toxicity and neoplasia (Talalay et al. 1990).

Mammalian cells have evolved elaborate mechanisms for protection against the toxic and neoplastic effects of electrophilic metabolites of carcinogens and reactive oxygen species. Glutathione transferases and high intracellular levels of GSH play an important role in providing such protection. Glutathione S-transferases are grouped into four classes, and Some of these forms act to prevent carcinogenesis by detoxifying carcinogens. GST M1 and T1 loss is associated with a greater susceptibility to some cancers.

The regulation of phase II enzymes seems to be mediated by the same enhancer element that contains AP-1-like sites (Prestera et al. 1993). They are transcriptionally- induced by low concentrations of a great variety of chemical agents. Some inducers are widely distributed in edible plants. In broccoli an isothiocyanate sulphoraphane is a very potent inducer of phase II enzymes and blocks mammary tumour formation in rats (Talalay et al. 1995).

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Detox Diet Basics

Detox Diet Basics

Our internal organs, the colon, liver and intestines, help our bodies eliminate toxic and harmful  matter from our bloodstreams and tissues. Often, our systems become overloaded with waste. The very air we breathe, and all of its pollutants, build up in our bodies. Today’s over processed foods and environmental pollutants can easily overwhelm our delicate systems and cause toxic matter to build up in our bodies.

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