Toxication

The process of being poisoned by a toxic substance

Toxication is the process by which a chemical compound becomes more toxic after undergoing metabolic transformation. This process is also known as metabolic activation. Toxication is a critical concept in toxicology and pharmacology, as it helps to understand how certain substances can become harmful to the body.

Mechanism

Toxication occurs when a non-toxic or less toxic substance is metabolized by the body into a more toxic form. This transformation is often mediated by enzymes, particularly those in the cytochrome P450 family. One of the most important enzymes involved in toxication is CYP3A4, which is responsible for the metabolism of many drugs and endogenous compounds.

CYP3A4 is a key enzyme in the metabolism of many substances.

Examples

Methanol

Methanol is a type of alcohol that is not highly toxic in its original form. However, when ingested, it is metabolized by the enzyme alcohol dehydrogenase into formaldehyde, which is then further oxidized to formic acid. Both formaldehyde and formic acid are highly toxic, leading to metabolic acidosis, visual disturbances, and potentially death.

The metabolic pathway of methanol to formaldehyde and formic acid.

Ethylene Glycol

Ethylene glycol, commonly found in antifreeze, is another example of a substance that becomes more toxic after metabolism. It is metabolized by alcohol dehydrogenase to glycolaldehyde, which is further metabolized to glycolic acid, glyoxylic acid, and finally oxalic acid. These metabolites can cause severe metabolic acidosis and renal failure.

The metabolic pathway of ethylene glycol to toxic metabolites.

Prevention and Treatment

Preventing toxication involves avoiding exposure to the parent compound or inhibiting the metabolic pathway that leads to the formation of toxic metabolites. For example, fomepizole and ethanol are used as antidotes for methanol and ethylene glycol poisoning because they inhibit alcohol dehydrogenase, preventing the formation of toxic metabolites.

Related pages

• Toxicology
• Metabolism
• Cytochrome P450
• Poisoning

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  CYP3A4 enzyme involved in drug metabolism

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  Methanol conversion to formaldehyde

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  Ethylene glycol toxication