10 Questions
What is the role of glutathione in phase II metabolism of xenobiotics?
To form glutathione S-conjugates that are excreted in urine and bile
What is the consequence of covalent binding of xenobiotics to macromolecules?
Cell injury and cytotoxicity
What is the role of epoxide hydrolase in the metabolism of xenobiotics?
To convert epoxides into less reactive forms
What is the result of the reaction catalyzed by glutathione S-transferases?
Formation of a glutathione S-conjugate
What is the effect of upregulation of glutathione S-transferase in tumors?
Resistance to chemotherapy
What is the role of cytochrome P450 in the metabolism of xenobiotics?
To activate xenobiotics into their reactive forms
What is the consequence of the binding of a reactive metabolite to a protein?
Altered antigenicity of the protein
What is the result of the reaction of some activated xenobiotics with DNA?
Mutation or carcinogenesis
What is the characteristic of epoxides formed during the metabolism of xenobiotics?
They are highly reactive and potentially mutagenic or carcinogenic
What is the effect of binding of a reactive metabolite to a protein and altering its antigenicity?
Initiation of autoimmune disease
Study Notes
Xenobiotics
- Xenobiotics are chemical compounds foreign to the body, including drugs, food additives, and environmental pollutants, as well as naturally occurring compounds in plant foods.
- Most xenobiotics are metabolized, mainly in the liver, in a process known as biotransformation.
Metabolism of Xenobiotics
- Xenobiotics are metabolized in two phases: Phase I and Phase II.
Phase I
- The major reaction of Phase I is hydroxylation catalyzed by a variety of monooxygenases, known as the cytochromes P450.
- Phase I reactions are broadly grouped into three categories: oxidation, reduction, and hydrolysis.
- Cytochrome P450 is a heme enzyme that plays a crucial role in Phase I reactions.
- At least half of the common drugs that we ingest are metabolized by isoforms of cytochrome P450.
Cytochrome P450
- Cytochrome P450 is a superfamily of enzymes that catalyze the oxidation of many xenobiotics.
- There are at least 57 genes encoding cytochrome P450 in the human genome.
- Cytochromes P450 are generally located in the endoplasmic reticulum of cells, especially in the liver.
- Many cytochromes P450 are inducible, which has important implications for drug interactions.
Phase II
- In Phase II, the hydroxylated species are conjugated with a variety of hydrophilic compounds such as glucuronic acid, sulfate, or glutathione.
- Types of Phase II reactions include glucuronidation, conjugation with amino acids, conjugation with glutathione, sulfation, acetylation, and methylation.
- Glutathione (G-SH) is important in the phase II metabolism of electrophilic compounds, forming glutathione S-conjugates that are excreted in urine and bile.
Toxic Effects of Xenobiotics
- Responses to xenobiotics can include toxic, immunological, and carcinogenic effects.
- Covalent binding of xenobiotics or their metabolites to macromolecules, including DNA, RNA, and protein, can lead to cell injury (cytotoxicity) and even cell death.
- Reactive metabolites of xenobiotics can bind to proteins, acting as haptens, and altering their antigenicity, potentially initiating autoimmune disease.
- Reactions of some activated xenobiotics with DNA are important in chemical carcinogenesis.
This quiz covers the basics of xenobiotics, including their definition, metabolism phases, and potential toxic effects. It also explores the importance of glutathione in xenobiotic metabolism.
Make Your Own Quizzes and Flashcards
Convert your notes into interactive study material.
Get started for free
