Xenobiotic Metabolic Enzymes: Bioactivation and Antioxidant Defense » książka
Xenobiotic Metabolic Enzymes: Bioactivation and Antioxidant Defense
ISBN-13: 9783030416812 / Angielski / Miękka / 2021 / 239 str.
Xenobiotic Metabolic Enzymes: Bioactivation and Antioxidant Defense
ISBN-13: 9783030416812 / Angielski / Miękka / 2021 / 239 str.
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1. Overview
1.1. Xenobiotics that humans are exposed to
1.1.1. Foods and drug; 1.1.2. Smoke and other chemicals
1.2. Metabolisms of foreign compounds before excretion
1.2.1 Activation enzymes: functionalization; 1.2.2. Detoxification enzymes:Conjugation; 1.2.3. Mechanism of enzyme actions
1.3. Potential toxicity of metabolic reactive intermediates
Components; 1.3.3. Cellular functional damages
1.4. Genetic and environment factors affecting xenobiotic metabolism
1.4.1. Genetic polymorphisms; 1.4.2. Environment and lifestyle
1.5. Defenses against oxidative stress mediated by foreign compounds
1.5.1. Modulation of metabolic enzymes for health benefits; 1.5.2. Inducers ofmetabolic enzymes
2. Foreign Compounds: Foods, Drugs and Other Chemicals
2.1. Foods
2.1.1. Heterocyclic amines; 2.1.2. Nitrosamines; 2.1.3. Polycyclic aromatic hydrocarbons;
2.1.4. Azo dyes; 2.1.5. α,β-unsaturated aldehydes; 2.1.6. Mycotoxin
2.2. Drugs
2.2.1. Acetaminophen; 2.2.2. Xanthine; 2.2.3. Terfenadine; 2.2.4. Menadione;
2.2.5. Diazepam2.3. Household products
2.3.1. Benzene; 2.3.2. Phenol
2.4. Smoke
2.4.1. Nitrosamines; 2.4.2. Nicotine and benzo(a)pyrene
2.5. Environmental chemicals
2.5.1. Diesel exhausts; 2.5.2. Arsenic; 2.5.3. Polychlorinated biphenyls; 2.5.4. Dioxins
3. Absorption, Metabolism and Excretion of Foreign Compounds
3.1. Lipophiles versus hydrophiles
3.2. Sites of Action
3.3. Cell Membranes
3.4. Transport Mechanisms
3.4.1. Passive diffusion; 3.4.2. Facilitated diffusion; 3.4.3. Active transport3.5. Metabolic Pathways
3.5.1. Activation metabolism; 3.5.2. Detoxification metabolism
3.6. Transport to external cell compartment
3.7. Metabolism precedes before excretion
3.8. Excretion
3.8.1. Renal excretion; 3.8.2. Reabsorption in the kidney; 3.8.3. Hepatic excretion;
3.8.4. Skin excretion4. Metabolism of Foreign Compounds
4.1. Activation metabolism
4.1.1. Functionalization reactions; 4.1.2. Metabolic reactive intermediates
4.2. Detoxification metabolism
4.2.1. Conjugation reactions; 4.2.2. Non-conjugation reactions4.3. Defenses against metabolites generated from bioactivation
4.3.1. Antioxidants; 4.3.2. Detoxifying enzymes
5. Bioactivation Metabolism: Activation Enzymes
5.1. Major activation enzymes
5.2. Oxidative enzymes
5.2.1. Cytochrome P450; 5.2.2. Flavin-Containing Monooxygenase;
5.2.3. Amine Oxidase; 5.2.4. Lipoxygenase; 5.2.5. Alcohol Dehydrogenase
5.2.6. Aldehyde Oxidase; 5.2.7. Xanthine Oxidase; 5.2.8. Peroxidase5.2.9. Prostaglandin H synthase
5.3. Oxidation at specific atom or group
5.3.1. Oxidation at carbon atom; 5.3.2. Oxidation at nitrogen atom
5.3.3. Oxidation of unsaturated hydrocarbon
5.4. Reductive enzymes
5.4.1. Nitroreductase; 5.4.2. Azoreductase; 5.4.3. Aldo-keto reductase
5.5. Reduction at specific atom or group
5.5.1 Reduction at nitrogen; 5.5.2 Reduction of carbonyl group5.6. Hydrolytic Enzymes
5.6.1. Carboxylesterase; 5.6.2 Epoxide Hydrolase
5.7. Hydrolysis at specific atom or group
5.7.1 Hydrolysis of ester; 5.7.2 Hydrolysis of amide
6. Functionalization Reactions Catalyzed by Activation Enzymes
6.1. Activation metabolism
6.1.1. Cytochrome P450; 6.1.2. Flavin monooxygenases; 6.1.3. Amine oxidases;
6.1.4. Nitroreductases; 6.1.5. Azoreductases; 6.1.6. Molybdenum hydroxylases;
6.1.7. Alcohol dehydrogenase; 6.1.8. Peroxidases; 6.1.9. Carboxylesterase
6.2. Oxidation reactions
6.2.1. Oxidation at carbon atom; 6.2.2. Oxidation at nitrogen atom;
6.2.3. Oxidation of unsaturated hydrocarbon
6.3. Reduction reactions
6.3.1. Reduction at nitrogen atom; 6.3.2. Reduction of carbonyl group
6.4. Hydrolysis reactions
6.4.1. Carboxylesterase; 6.4.2. Epoxide Hydrolase
7. Detoxifying Metabolism: Detoxification Enzymes7.1. Excretors
7.2. Conjugation enzymes
7.2.1. Uridine-diphosphate-glucuronosyltransferases ; 7.2.2. Glutathione S-transferases;
7.2.3. Sulfotransferases; 7.2.4. N-acetyltransferases; 7.2.5. Methyltransferases;
7.2.6. Acyltransferases
7.3. Non-conjugation enzymes
7.3.1 Quinone reductase; 7.3.2. Epoxide hydrolases
8. Conjugation Reactions Catalyzed by Detoxification Enzymes
8.1. Detoxification reactions
8.1.1. Conjugation enzymes; 8.1.2. Non - conjugation enzymes
8.2. Conjugation reaction at specific atom or group
8.2.1. Conjugation at O atom; 8.2.2. Conjugation at N atom; 8.2.3. Conjugation at Catom; 8.2.4. Conjugation at S atom; 8.2.5. Conjugation of carboxylic acid
9. Reactive Intermediates Generated from Bioactivation
9.1. Reactive intermediates
9.1.1. Reactive oxygen / nitrogen species; 9.1.2. Free radicals
9.1.3. Positively or neutral charged electrophilic compounds
9.2. Foreign compounds that form toxic reactive intermediates
9.2.1. Drugs; 9.2.2. Herbs and dietary supplements; 9.2.3. Other chemicals
9.3. Metabolic enzymes involved in reactive intermediate formation
9.3.1. Functionalization reactions; 9.3.2. Conjugation reactions
9.4. Oxidation reactions involved in reactive intermediate formation
9.4.1. Cytochrome P450 catalysis; 9.4.2. Peroxidase catalysis
9.5. Factors affecting reactive intermediate accumulation
9.6. Reactive intermediate interacting with proteins, DNA and lipids
9.6.1. Protein adducts; 9.6.2. DNA adducts; 9.6.3. Lipid peroxidation
10. Electrophilic Nature of Metabolic Reactive Intermediates
10.1. Reactive intermediates
10.2. Reactive oxygen species10.3. Functional groups of electrophilic reactive intermediates
10.4. Cellular nucleophilic sites involving reactive intermediate binding
10.4.1. Protein; 10.4.2. DNA; 10.4.3. Lipid
10.5. Defenses against metabolic reactive intermediates
10.5.1. Detoxification enzymes; 10.5.2. Antioxidant enzymes; 10.5.3. Glutathione
10.5.4. Vitamins E and C and carotene
11. Oxidative Stress Mediated by Reactive Intermediates
11.1. Reactive chemical intermediates11.1.1. Exogenous metabolites; 11.1.2. Endogenous metabolites
11.2. Reactive oxygen species (ROS)
11.2.1. ROS generated from mitochondria; 11.2.2. ROS generated from metabolicbioactivation
11.3. Reactive nitrogen species
11.4. Oxidative stress mediated damages
11.5. Defense against oxidative stress
12. Xenobiotics Bioactivation - Mediated Cellular Damages
12.1. Exhibition of foreign compound toxicity
12.1.1. Natural toxicity; 12.1.2. Metabolic bioactivation; 12.1.3. Induced toxicity
12.2. Oxidative stress generated from metabolic reactive intermediates12.3. Interactions with cellular components
12.3.1. Interactions with proteins; 12.3.2. Interactions with DNA; 12.3.3. Interactions
with lipids
12.4. Cellular functional damages
12.4.1. Mitochondrial function intervention; 12.4.2. Interactions with ion transporters
12.4.3. Interference with enzymatic functions; 12.4.4. Immune suppression and
stimulation effects; 12.4.5. Chemical carcinogenesis; 12.4.6. Age-related disorders
13. Nrf2/ARE Pathway Defense Against Oxidative Stress
13.1. Oxidative stress and biochemical dysregulation
13.2. Role of Nrf2 - ARE pathway
13.3. Nrf2 – Keap1-ARE pathway in the absence of oxidative stress
13.4. Nrf2-Keap1-ARE pathway in the presence of oxidative stress
13.5. Activation of Nrf2-ARE pathway
13.6. Nrf2 – ARE pathway on cytoprotection13.6.1. Induction of detoxification enzymes; 13.6.2. Phytochemicals for cytoprotection
13.6.3. Dietary phytochemicals
14. Genetic Variations and Polymorphisms of Metabolic Enzymes
14.1. Genetic polymorphisms affecting metabolic enzymatic functions
14.2. Effects of enzyme polymorphism on xenobiotics - mediated toxicity
14.3. Polymorphisms of detoxification enzymes: transferases
14.3.1. Glutathione S-transferase polymorphism; 14.3.2. UDP-glucuronosyltransferase
polymorphism; 14.3.3. Sulfotrasferase polymorphism; 14.3.4. N-Acetyltransferasepolymorphism; 14.3.5. Methyltransferase polymorphism
14.4. Polymorphisms of detoxification enzymes: non-transferases
14.4.1. Quinone reductase and oxidoreductase polymorphisms; 14.4.2. Epoxide
hydrolase polymorphism
15. Enzyme Polymorphisms Affecting Xenobiotic Toxicity
15.1. Differential susceptibility to potentially xenobiotic toxicity
15.1.1. Susceptibility to drug toxicity; 15.1.2. Susceptibility to diverse toxicity
15.2. Enzyme polymorphisms affecting xenobiotic metabolisms
15.2.1. Cytochrome P450 (CYP450); 15.2.2. Alcohol dehydrogenase and aldehyde
dehydrogenase;15.2.3. Glutathione-S-transferase; 15.2.4. UDP-glucuronosyltransferase
15.3. Species differences affecting foreign compound metabolisms
15.3.1. Susceptibility to aflatoxin toxicity in humans, but not in mice; 15.3.2.
Resistance to tamoxifen toxicity in humans, but not in rats; 15.3.3. 4-Ipomeanoltoxicity response to humans versus rodents
16. Inducibility of Foreign Compound Metabolic Enzymes
16.1. Inducibility of metabolic enzymes
16.2. Features of metabolic enzyme inducers16.3. Monofunctional and bifunctional inducers
16.4. Inducer - enzyme interactions
16.4.1. Michael reaction acceptors; 16.4.2. Unsaturated carbon - carbon bonds;
16.4.3. Phenolic hydroxyl groups
16.5. Antioxidant response element
17. Induction of Enzymes for Health Benefits
17.1. Metabolic enzyme modulation
17.2. Activation enzyme modulation
17.3. Detoxification enzyme modulation17.4. Balance between activation and detoxification
17.5. Enzyme modulation as a defense against potential toxic effects
17.6. Defense against xenobiotic toxicity
17.7. Mechanism of metabolic enzyme modulation
17.8. Lifestyle modulation of metabolic enzymes
17.8.1. Alcohol; 17.8.2. Cigarette smoke
18. Diversity of Metabolic Enzyme Modulators
18.1. Isothiocyanates
18.2. 1,2-dithiole-3-thione and its derivatives
18.3. Indole-3-carbinol
18.4. Polyphenols, flavonoids and isoflavones18.5. Organosulfur compounds
18.6. Terpenes and terpenoids
18.7. Geniposide
19. Dietary Inducers of Detoxification Enzymes
19.1. Cruciferous vegetables
19.1.1. Sulfur - containing compounds; 19.1.2. Non-sulfur-containing compounds
19.2. Allium vegetables
19.2.1. Thiols; 19.2.2. Diallyl sulfides
19.3. Root vegetables
19.3.1. Flavonoids; 19.3.2. Carotenoids; 19.3.3. Curcumin19.4. Fruits
19.4.1. Polyphenols; 19.4.2. Triterpenes;
19.5. Green tea and algae
19.5.1. Green tea; 19.5.2. Algae
This book provides a comprehensive, organized, and concise overview of Xenobiotic Metabolic Enzymes and their health implications. The subjects addressed are broad in scope with an emphasis on recent advances in research on biochemical and biomedical aspects of these enzymes. The xenobiotics discussed include not just drugs, but also food, smoke, and other environmental chemicals.
The subjects covered in this work include: metabolic enzymes and their catalyzed reactions, reactive intermediates generated from metabolic activation, oxidative stress mediated by electrophilic reactive intermediates, bioactivation - mediated cellular and functional damages, activation of Nrf2 – ARE pathway, genetic variations affecting metabolic enzyme expression, enzyme polymorphisms affecting xenobiotic - mediated toxicity, induction of metabolic enzymes for health benefits, and a diversity of metabolic enzyme modulators.
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