Xenobiotics and Redox Metabolism

By Dr Ananya Mandal, MD

What are xenobiotics?

Most of the ingested material and compounds are foods and drugs. Some of these cannot be utilized by the body as foods. These may be harmful if they accumulated in cells, as they have no metabolic function. These are called xenobiotics.

Where does the term xenobiotic come from?

The tem xenobiotic is derived from Greek words “xenos” meaning foreigner, stranger and “bios” meaning life added to the Greek suffix for adjectives “tic”.

Examples of xenobiotics

Xenobiotics include:

  • synthetic drugs
  • natural poisons
  • food additives
  • environmental pollutants
  • antibiotics etc.

More than 200,000 xenobiotics have been identified and these are metabolized and detoxified by xenobiotic-metabolizing enzymes.

Xenobiotic metabolism

In humans xenobiotics are metabolized by cytochrome P450 oxidases, UDP-glucuronosyltransferases, and glutathione ''S''-transferases. These enzymes acts in three stages to firstly oxidize the xenobiotic (phase I) and then conjugate water-soluble groups onto the molecule (phase II). The molecules from phase II that are water-soluble are then pumped out of cells and in multicellular organisms may be further metabolized before being excreted (phase III).

Two major phases of xenobiotic metabolism

Metabolism of xenobiotics thus occurs in two major phases.

Phase I

This process is characterized by hydroxylation. This is carried out by a variety of monooxygenases, also known as cytochrome P450s. These Cytochrome P450s catalyze reactions that introduce one atom oxygen delivered from molecular oxygen into the substrate, yielding a hydroxylated product.

Phase II

In this phase the hydroxylated species are conjugated with a variety of hydrophilic compounds such as glucuronic acid, sulfate or gluthione. This makes the compounds water soluble that can be easily eliminated from the body.

Xenobiotics and oxidative stress

A related problem for aerobic organisms is oxidative stress caused by reactive oxygen free radicals. Oxidative stress is a large increase in the cellular reduction potential, or a large decrease in the reducing capacity of the cellular redox couples. This process involves formation of disulfide bonds during protein folding that leads to production of reactive oxygen species such as hydrogen peroxide.

Free radicals cause a chain reactions leading to consecutive oxidation. These radicals attack molecules like fat, protein, DNA, sugar etc.

Free radicals are removed by antioxidant metabolites such as glutathione and enzymes such as catalases and peroxidases. Antioxidants neutralize free radicals before they can attack cell proteins, lipids and carbohydrates. They inhibit and delay the oxidative process.

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

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Further Reading

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