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Questions and Answers
Where does the liver play a major role in biotransformation?
Where does the liver play a major role in biotransformation?
What type of reactions do Phase 1 enzymes catalyze?
What type of reactions do Phase 1 enzymes catalyze?
What is the primary function of Cytochrome P450?
What is the primary function of Cytochrome P450?
What is the result of oxidative deamination?
What is the result of oxidative deamination?
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What is the location of Cytochrome P450 enzymes?
What is the location of Cytochrome P450 enzymes?
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What is the effect of Phase 2 reactions on xenobiotics?
What is the effect of Phase 2 reactions on xenobiotics?
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What is a factor that affects xenobiotic metabolism?
What is a factor that affects xenobiotic metabolism?
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What is the role of NADPH in Cytochrome P450-dependent reactions?
What is the role of NADPH in Cytochrome P450-dependent reactions?
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What type of enzymes catalyze Phase 2 reactions?
What type of enzymes catalyze Phase 2 reactions?
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What is the purpose of biotransformation?
What is the purpose of biotransformation?
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What is the primary site of metabolism for toxicants?
What is the primary site of metabolism for toxicants?
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What is the result of the metabolism of toxicants?
What is the result of the metabolism of toxicants?
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What is the role of cytochrome P450 proteins in microsomes?
What is the role of cytochrome P450 proteins in microsomes?
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What is the function of peroxisomes in xenobiotic metabolism?
What is the function of peroxisomes in xenobiotic metabolism?
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What is the effect of genetic variation on xenobiotic metabolism?
What is the effect of genetic variation on xenobiotic metabolism?
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What can influence the activity of enzymes involved in xenobiotic metabolism?
What can influence the activity of enzymes involved in xenobiotic metabolism?
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Study Notes
Toxicants Metabolism
- Toxicants (xenobiotics) are catalyzed by enzymes to form metabolites with modified structures.
- Liver is the major site of metabolism, but other sites include plasma, kidney, lung, and gut wall.
- Metabolism can result in:
- Less toxic chemicals (metabolites)
- More toxic chemicals (metabolites)
- Chemicals with different types of effects or toxicity
Sites of Metabolism
- Liver: ideally placed to intercept ingested toxins, has a major role in biotransformation
- Other sites: plasma, kidney, lung, gut wall
- Enzymes occur where needed, e.g. Cytochrome P450 in liver microsomes
The Liver
- Hepatocytes (liver cells) contain microsomes with Cytochrome P450
- Biotransformation occurs in the liver, converting lipophilic toxicants to hydrophilic metabolites
Biotransformation Reactions
- Phase 1 reactions: functionalization of xenobiotics to form reactive groups
- Hydroxylation
- Oxidation
- N-dealkylation
- Oxidative deamination
- Phase 2 reactions: conjugation of reactive groups with endogenous molecules to form excretable products
- Conjugations with glucuronic acid, sulphate, acetyl groups, and glutathione
Phase 1 Enzymes
- Cytochrome P450 (CYP): most important enzyme in xenobiotic metabolism, membrane-bound and localized in smooth endoplasmic reticulum
- Flavin-containing monoxygenases (FMO)
- Epoxide hydrolases
- Alcohol/Aldehyde Dehydrogenases
- Monoamine Oxidases
- Xanthine oxidase
Cytochrome P450
- Divided into families, subfamilies, and isoforms (e.g. CYP1, CYP2, CYP3)
- Requires NADPH and O2 for reactions
- Plays a key role in the metabolism of xenobiotics
Factors Affecting Metabolism
- Age: reduced metabolism in aged and children
- Sex: women more sensitive to ethanol
- Species: different metabolism rates among species
- Clinical or physiological conditions: can affect metabolism rates
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Description
This quiz covers the process of biotransformation of toxicants, including the role of enzymes, liver metabolism, and genetic variations. Learn about the different routes of metabolism and how they affect the action of toxicants.