Biochemistry of Drug Metabolizing Enzymes

Trends and Challenges

1st Edition - May 28, 2022
Editors: Muhammad Sajid Hamid Akash, Kanwal Rehman
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 5 1 2 0 - 3
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 5 1 2 1 - 0

Biochemistry of Drug Metabolizing Enzymes: Trends and Challenges is a complete and well-integrated reference on their mechanisms of action, their role in diseases, agents responsib… Read more

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Biochemistry of Drug Metabolizing Enzymes: Trends and Challenges is a complete and well-integrated reference on their mechanisms of action, their role in diseases, agents responsible for their deactivation, and their malfunction. Chapters explain the biochemistry of DMEs, including biochemical activation, functions, computational approaches, different contaminants on the action and function of DMEs, and describe the importance of DMEs in the drug development process. Conditions covered include metabolic diseases, cardiovascular diseases, neurological diseases, physiological diseases, xenobiotics and inflammatory responses, and their contribution in the malfunctioning of drug metabolizing enzymes.

This book is the perfect resource for pharmacology and biochemistry researchers to understand the principles of DMEs. Researchers in the corporate environment will also benefit from the comprehensive list of diseases associated with malfunction of DMEs.

Cover
Title page
Table of Contents
Copyright
Contributors
Chapter 1: Biochemical activation and functions of drug-metabolizing enzymes
Abstract
1: Introduction
2: Phase I drug-metabolizing enzymes
3: Phase II drug-metabolizing enzymes
4: Phase III biotransformation reactions
5: Conclusion
References
Chapter 2: Computational approaches for drug-metabolizing enzymes: Concepts and challenges
Abstract
1: Introduction
2: Metabolism in human body
3: Drug-metabolizing enzymes
4: Computational approaches
5: Data modeling
6: Databases
7: Softwares
8: Stereoselectivity
9: Regioselectivity
10: Inadequacies of current in silico method
11: Conclusion and future perspectives
References
Chapter 3: Role of drug-metabolizing enzymes in biotransformation of drugs
Abstract
1: Introduction
2: Biotransformation reactions and drug metabolizing enzymes
3: Conclusion
Conflict of interest
References
Chapter 4: Emerging environmental contaminants and drug-metabolizing enzymes
Abstract
1: Introduction
2: Pharmaceuticals and personal care products
3: Plasticizers
4: Pesticides
5: Surfactants as emerging contaminants
6: Emerging environmental contaminants and their enzyme-assisted biodegradation
7: Mechanism and function of drug-metabolizing enzymes
8: EECs and drug-metabolizing enzymes induction
9: Conclusion
References
Chapter 5: Drug-metabolizing enzymes and fate of prodrugs: From function to regulation
Abstract
1: Introduction
2: Prodrug
3: Biotransformation reactions
4: Drug-metabolizing enzymes
5: Conclusions
References
Chapter 6: Hormones and drug-metabolizing enzymes: From function to regulation
Abstract
1: Introduction
2: Drug metabolism of metabolizing enzymes
3: Impact of hormones on drug-metabolizing enzymes
4: Physiological states and disorders causing hormonal changes
5: Conclusion
References
Chapter 7: Receptors and drug-metabolizing enzymes: From function to regulation
Abstract
1: Introduction
2: Drug-metabolizing enzymes
3: Phase I biotransformation
4: Phase II biotransformation
5: Phase III biotransformation
6: Receptors and their functional impairment with DMEs
7: Regulation of DMEs biotransformation by xenobiotic receptors PXR and CAR
8: Receptors and their functional impairment with DMEs
9: Linking of xenobiotic NRs to drug interactions
10: Cross-talk between PXR and CAR
11: Conclusion remarks
References
Chapter 8: Biochemistry of cathepsins enzymes and their metabolic activity in the lysosome
Abstract
Acknowledgment
1: Introduction
2: Cathepsins in the lysosome
3: Cathepsins synthesis
4: M6P route for sorting and regulatory mechanisms
5: Secretion of cathepsins
6: Physiological function of cathepsins inside the lysosomes
7: Mediate drug metabolism
8: Pathophysiology of cathepsins
9: Conclusion
References
Chapter 9: Fate of drug-metabolizing enzymes in metabolic diseases
Abstract
1: Introduction
2: Human drug-metabolizing CYP450 enzymes
3: Enzyme inhibition and induction
4: Factors affecting enzyme activity
5: Fate of drug metabolism in metabolic diseases
6: Challenges and strategies related to DMEs in metabolic disorder
7: Conclusion
References
Chapter 10: Fate of drug-metabolizing enzymes in cardiovascular diseases: Concepts and challenges
Abstract
1: Introduction
2: Expression of phase I and phase II drug-metabolizing enzymes in cardiovascular system
3: Fate of CYP1B1 in cardiovascular pathology
4: Pharmacogenomics of cardiovascular diseases and cardiovascular drugs
5: Gender-specific variations of DMEs in pharmacotherapy of cardiovascular diseases
6: Conclusion
References
Chapter 11: Fate of drug-metabolizing enzymes in neurological diseases: Challenges and strategies
Abstract
1: Introduction
2: CYP450 system and drug metabolism
3: Nomenclature of CYPs
4: Classification of CYPs
5: CYP450 and drug metabolism
6: Drug metabolizing enzymes in central nervous system
7: Implications of DME on neuropsychiatric diseases
8: CYPs and psychiatric diseases
9: Role of CYP450 in ischemic brain injury
10: Brain CYPs and drug addiction
11: Brain CYPP2D and chronic antidepressant therapy
12: Fate of cytochrome P450 in epilepsy
13: CYP-450 and Alzheimer’s disease
14: Pathological and clinical correlates of CYP450 in implications of Parkinson’s disease
15: Mutation spectrum in DME and its clinical manifestations
16: Current challenges and future perspective
17: Conclusion
Conflict of interest
Author contributions
References
Chapter 12: Impact of physiological factors on drug-metabolizing enzymes: From function to regulation
Abstract
1: Introduction
2: Drug metabolism
3: Pathways of drug metabolism
4: Factors affecting drug metabolism
5: Physiological factors affecting drug metabolism
6: NADPH: CYP450 oxidoreductase (POR)
7: Conclusion
Conflict of interest
References
Chapter 13: Xenobiotics and drug-metabolizing enzymes: Challenges and strategies
Abstract
1: Introduction
2: Drug-metabolizing enzymes
3: Phases of drug-metabolizing enzymes
4: Types of drug-metabolizing enzymes
5: Xenobiotics metabolism
6: Gut microbiota and metabolic process of xenobiotics
7: Challenges
8: Factors affecting drug metabolism
9: Strategies
10: Conclusion
References
Chapter 14: Drug-metabolizing enzymes and inflammatory responses
Abstract
1: Introduction
2: Gene expression and inflammatory processes
3: Regulation of DMEs in inflammatory disorders
4: Effect of inflammation on CYP regulation
5: Mechanism of CYPs regulation
6: Signaling pathways associated with CYP regulation
7: Regulation of mRNA expression of CYP enzymes
8: Role of CYPs in inflammatory responses
9: Regulation of phase II enzymes in inflammation
10: Conclusion
References
Chapter 15: Polymorphisms in drug-metabolizing enzymes: Challenges and strategies
Abstract
1: Introduction
2: Evolution of pharmacogenomics
3: Interindividual drug responses
4: Genetic polymorphisms of DMEs
5: Polymorphisms in drug transporter genes
6: Polymorphisms of DMEs and their impact on drug-drug interactions
7: Strategies in pharmacogenomic research and development
8: Role of bioinformatics in pharmacogenomic research
9: From scientific evidence to clinical practice
10: Conclusion
References
Chapter 16: Modulation of human microbiome and drug metabolism
Abstract
1: Introduction
2: Gut microbiota and drug pharmacokinetics
3: Modification of gut microbiota
4: Prospects
References
Chapter 17: Bioanalytical techniques for prediction of metabolic activity of drug-metabolizing enzymes
Abstract
1: Introduction
2: Metabolomics approaches
3: Models for drug metabolism evaluation
4: Approaches for metabolite quantification
5: Bioanalytic techniques for metabolites identification
6: Other suitable approaches for metabolite identification
7: Conclusion
References
Chapter 18: Role of pharmacogenomics for prediction of personalized medicines
Abstract
1: Introduction
2: Factor affecting the drug response
3: Pharmacogenomics biomarker
4: Tools that modify the risk prediction and risk assessment
5: Applications of pharmacogenomics and personalized medicine
6: Pharmacogenomics impact on personalized medicine
7: Conclusion
References
Chapter 19: Dietary sources of drug-metabolizing enzymes: From production to regulation
Abstract
1: Introduction
2: Regulation of drug-metabolizing enzymes
3: Association of food products with regard to drug-metabolizing enzymatic action
4: Fruits interaction with metabolic enzymes
5: Vegetable interaction with metabolic enzymes
6: Common drug and nutrient interactions
7: Conclusion
References
Chapter 20: Vitamin deficiencies and drug-metabolizing enzymes: Challenges and strategies
Abstract
1: Introduction
2: Impact of vitamin deficiencies on drug-metabolizing enzymes
3: Impact of vitamin deficiencies on drug metabolism
4: Conclusion
References
Chapter 21: Fate of drug-metabolizing enzymes in malnutrition: Challenges and strategies
Abstract
1: Introduction
2: Drug metabolism
3: Protein calorie malnutrition
4: Effect of low carbohydrate diet on drug-metabolizing enzymes
5: Effect of fat-free diet on drug-metabolizing enzymes
6: Effect of mineral deficiency on drug-metabolizing enzymes
7: Effect of vitamin deficiency on drug-metabolizing enzymes
8: Effect of iron deficiency on drug-metabolizing enzymes
9: Conclusion
References
Chapter 22: Drug-metabolizing enzymes and oxidative stress
Abstract
1: Introduction
2: Generation of reactive oxygen species during drug metabolism
3: Oxidative stress generated by drug metabolites
4: Endogenous defense against oxidative stress
5: Antioxidant therapy
6: Conclusion
References
Index

Muhammad Sajid Hamid Akash

Dr. Akash is currently working as associate professor and chairman at Department of Pharmaceutical Chemistry, Government College University Faisalabad (GCUF), Pakistan. He got his bachelor and master’s degrees in pharmacy from Bahauddin Zakariya University Multan, Pakistan and PhD degree in Pharmaceutical Analysis from Zhejiang University, China. Currently, he is focusing on investigating the effect of EDCs on various molecular and metabolic pathways that are involved in metabolic disorders and the treatment strategies of these EDCs-induced metabolic disorders funded by Higher Education Commission (HEC) of Pakistan. His Research work is the cutting edge and worthy of extension in developing countries like Pakistan, where it can be most beneficial and cost-effective especially for diabetic patients. Based on his significant scientific contributions in the field of Pharmaceutical Sciences, he has been awarded “Research Productivity Award” from Pakistan Council for Science and Technology (PCST), PAS Gold Medal from Pakistan Academy of Sciences and A.R. Shakoori Gold Medal from Zoological Society of Pakistan.

Affiliations and expertise

associate professor and chairman at Department of Pharmaceutical Chemistry, Government College University Faisalabad (GCUF), Pakistan.

Kanwal Rehman

Dr. Kanwal Rehman PhD is working as Associate Professor at Department of Pharmacy in The Women University, Multan, Pakistan. Dr. Kanwal Rehman received her PhD in Pharmacology and Toxicology from Zhejiang University, Hangzhou, China in 2015. She nurtures a keen interest in pathogenesis of metabolic disorders like diabetes mellitus, obesity, and new therapeutic modalities for its treatment. Other work includes detection of environmental pollutants and their cytotoxic effects. She has published about 135 articles. She has also published 50 book chapters with international publishers and 4 books with Springer-Nature. Currently, she is focusing on the investigation of role of pharmacogenomics based upon gene polymorphism on various molecular and metabolic pathways that are involved in mitogenic disorders and treatment strategies like natural biogenic compounds against different risk factors of metabolic disorders including pancreatitis, cardiometabolic disorders and hormonal imbalance. Dr. Kanwal Rehman has also been awarded Research productivity award by Pakistan Council for Science and Technology (PCST), Pakistan.

Affiliations and expertise

Associate Professor at Department of Pharmacy in The Women University, Multan, Pakistan.