The Ability of the human organism to neutralize Pollutants, foreign substances and drugs, which are brought to the body or harmful substances produced by itself. This detoxification process is ensured by different enzymatic systems and works in two phases. First of there is an activation of the toxic substances by phase-I-enzymes of the cytochrome P450 family, the resulting metabolites are detoxified by phase-II-enzymes.
Products of the phase I mostly are more aggressive than the primary substances, so the detoxification in step two is essential.
In the phase II detoxification system are not only the multifunctional glutathione transferases (GSTs) included,also there are special transferases, e.g. n-acetylated transferases (NAT), sulfotransferases and epoxides (e.g. microsomal epoxides). There task is the conjugation of potential mutagenic and cytotoxic, DNA-reactive substances with glutathone, to get them soluble in water and more able for excretion. In this process there emerge oxygen radicals, which have to be absorbed by superoxide dismutases. In some cases is a parallel examination of SODs advisable.
Unfavourable genetic equipment of the detoxification system can cause adverse drug reactions and promote the development of various diseases.

The Glutathione-S-Transferases

Especially the soluble, cytosolic enzymes like GSTM3, GSTM1 and GSTP1 have clinical relevance. The GSTM1 particularly occurs in liver and lymphocytes, but also in all tissues. The main task is the detoxification of electrophilic substances, e.g.

The Glutathione-S-Transferase M3 is closely related to GSTM1 with a similar substrate spectrum. GSTT1 detoxifies - same like GSTM1 - harmful substances by conjugation with reduced glutathione. Main substrate are likewise electrophilic and hydrophilic substances. Its primary substances to detoxify are halogenides and epoxides (e.g. dichloromethane, bromodichlormethane, ethylendioxid and methylobromide, various carcinogens, e.g. from tobacco smoke).
Substrates of GSTP1 are drugs and its metabolites like paracetamol ifosfamide and thiotepa. But also it detoxifies substances like polycyclic aromatic hydrocarbons( PAH's, especially benzpyrendiolepoide), from tobacco smoke, wood smoke, coal tar or well-done meat.

Recommended tests:
Cytochrom P450

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