Xenobiotics Flashcards
Importance of xenobiotics
• Understanding the mechanisms of xenobiotic metabolism can lead to development of a genetically modified microorganism or plants – containing genes that encodes enzymes for the metabolism of specific compounds that can be used to convert potentially hazardous pollutants to harmless compounds
– that can be used for biosynthesis of drugs and other chemicals
Means stranger
Xenos
2 Principal classes of xenobiotics
A. Exogenous
• Drugs • Chemical carcinogens • Various compounds that found their way into our environment •
Polychlorinated biphenyls (PCBs), insecticides and other pesticides • Naturally occurring compounds in plant foods
B. Endogenous
• Bilirubin. Bile acids. Steroids, Eicosanoids
It renders the xenobiotic to be readily excreted in the bile or urine
Has 2 phases
Xenobiotic Metabolism
inert substance (most of the times)
Active xenobiotic
Inert xenobiotic
active metabolite (occasionally)
It is All the biochemical reactions involved in the conversion of foreign, toxic, and water-insoluble molecules to non-toxic, water-soluble and excretable forms
The purpose of which is to increase their water solubility (polarity) and thus excretion from the body.
BIOTRANSFORMATION DETOXIFICATION REACTION
Entoxification reaction
reactions may instead increase the toxicity of a foreign compound
(Metabolic Activation)
Phase I reactions can also convert xenobiotics from inactive to biologically active compounds.
What is phase 2 in xenobiotics metabolism
conjugation reactions can convert the active products of Phase I reactions to active or inactive species. Which are then excreted in urine or bile.
the conjugation may increase the biological activity of xenobiotic
(Metabolic Action)
Phase I Metabolism:
Enzymatic Reactions: Phase I metabolism involves enzymes like cytochrome P450 (CYP450) that catalyze reactions such as oxidation, reduction, and hydrolysis.
Functionalization: These reactions often add or expose functional groups (e.g., hydroxyl, amino, or carboxyl groups) on the xenobiotic molecule, increasing its reactivity.
Prodrug Activation: In some cases, phase I metabolism converts inactive prodrugs into their active forms, which can then exert pharmacological effects.
Example: The conversion of ethanol to acetaldehyde by alcohol dehydrogenase (ADH) is a phase I reaction in alcohol metabolism
Phase II Metabolism:
Conjugation Reactions: Phase II metabolism involves conjugation reactions where molecules like glucuronic acid, sulfate, glutathione, or amino acids are added to the xenobiotic.
Increased Water Solubility: Conjugation makes xenobiotics more water-soluble, aiding their excretion through urine or bile.
Detoxification: Conjugated xenobiotics are often less toxic and more easily eliminated from the body compared to their phase I metabolites.
Example: Glucuronidation is a common phase II reaction where glucuronic acid is added to xenobiotics to increase their water solubility.
So, in simpler terms, phase I metabolism makes the xenobiotic smaller and more reactive, while phase II metabolism adds something to help the body get rid of it easily. This two-step process is like breaking down and then packaging up the xenobiotics for removal from the body