Cholesterol: From Chemistry and Biophysics to the Clinic - 신간POD상품

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Editors: Anna Bukiya, Alex Dopico
Pages: 1058
Published: April 26, 2022
Imprint: Academic Press
ISBN: 9780323858571

Description

With Cholesterol, Drs. Anna Bukiya and Alex Dopico have compiled a comprehensive resource on biological and clinical aspects of cholesterol, spanning biophysics and biochemistry, as well as the latest pharmacological discoveries employed to tackle disorders associated with abnormal cholesterol levels. Early chapters on basic biology offer guidance in cholesterol lab chemistry, cholesterol metabolism and synthesis, molecular evolution of cholesterol and sterols, cholesterol peptides, and cholesterol modulation. Chapters on cellular and organismal development discuss cholesterol transport in blood, lipoproteins, and cholesterol metabolism; cholesterol detection in the blood; cellular cholesterol levels; hypercholesterolemia; and the role of cholesterol in early human development. Pathophysical specialists consider familial hypobetalipoproteinemia, critical illness and cholesterol levels, coronary artery disease, CESD, cholesterol and viral pathology, cholesterol and neurodegenerative disorders, and cholesterol and substance use disorders. A final section examines pharmacology of drug delivery systems targeting cholesterol related disorders, cholesterol receptors, cholesterol reduction, statins, citrate lyase, cyclodextrins, and clinical management. Cholesterol: From Biophysics and Biochemistry to Pathology and Pharmacology empowers researchers, students, and clinicians across various disciplines to advance new cholesterol-based studies, improve clinical management, and drive drug discovery.

Key Features

Readership

Life science researchers in biochemistry, biophysics, molecular biology, or cell biology; clinical chemists and pharmaceutical scientists; analytical chemists; food scientists; nutritionists. Clinicians and students

Table of Contents

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Afterword
Section 1: Cholesterol chemistry and cell function
Chapter 1: Cholesterol chemistry and laboratory synthesis
Abstract
Introduction
Cholesterol structural characterization
Cholesterol laboratory synthesis
Concluding remarks
References
Chapter 2: Molecular evolution of cholesterol and other higher sterols in relation to membrane structure
Abstract
Acknowledgments
Introduction: The overlooked lipids
Key features of the cholesterol molecule
Evolution and streamlining of a molecule
Phase equilibria in lipid membranes
Cholesterol and lipid membrane phase equilibria: The liquid-ordered phase
Cholesterol, transverse membrane order, permeability, and mechanics
Cholesterol and lateral membrane organization
Other higher sterols: Universality in sterol function
A case study: Cholesterol, lateral membrane structure, and the functioning of Na+/K+-ATPase
Cholesterol and membrane evolution
References
Chapter 3: Role of cholesterol in maintaining the physical properties of the plasma membrane
Abstract
Acknowledgments
Introduction
Phase diagram for cholesterol/phospholipid mixtures
Basic membrane physical properties and how cholesterol regulates them
Lateral organization of membranes: Effect of cholesterol
New information from the saturation recovery electron paramagnetic resonance stretched exponential function approach
Concluding remarks
References
Chapter 4: The fundamental interaction of cholesterol with lipid membranes: The umbrella model
Abstract
Acknowledgments
Introduction
Maximum solubility of cholesterol in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) bilayers
The umbrella model
Monte Carlo simulation of chemical potential of cholesterol using multibody interactions
A family of small headgroup molecules: Sterols, ceramides, and diacylglycerols
Molecular dynamics (MD) simulation of the umbrella effect
Measurement of the chemical potential of cholesterol in PC bilayers
Concluding remarks
References
Chapter 5: Model peptides and cholesterol
Abstract
Acknowledgment
On the energy and entropy parameters of the free energy of the membrane
References
Chapter 6: Cholesterol and ceramide: An unlikely pair
Abstract
Acknowledgments
Introduction: Membrane heterogeneity
Sphingolipids and cholesterol: Biological impact
Sphingolipids and cholesterol: Membrane biophysics
Cholesterol and ceramide in fluid membranes
Conclusions and future perspectives
References
Chapter 7: Cholesterol-recognizing amino acid consensus motifs in transmembrane proteins: Comparative analysis of in silico studies and structural data
Abstract
Introduction
Cholesterol: Bifacial structure, multifaceted functions
Cholesterol footprint on a membrane protein: Starting the investigation
CARC and CRAC algorithms: Basic principles at work
Cholesterol-binding motifs in 3D: What structural studies reveal
Moving to the 3rd dimension
Conclusion
References
Chapter 8: Effects of cholesterol on the GPCR AT1 receptor and its interplay with AT1 antagonists
Abstract
Introduction
Experimental results and their discussion
Cholesterol influence on the physicochemical properties of the cell membrane in the presence of AT1R and sartans
Molecular dynamics (MD) simulations on AT1R embedded in a DPPC:Cholesterol (60:40 mol%) bilayer reveal a putative binding site for AT1R blockers on the receptor
Conclusions
References
Chapter 9: Principles of cholesterol regulation of ion channels
Abstract
Acknowledgments
Introduction
Lipids as structural components and functional regulators of membrane proteins
A thermodynamic consideration of lipid-binding sites on ion channels and their generic effects on the gating of the channels
Cholesterol-binding sites on ion channels
Functional impact of cholesterol on the activities of ion channels
Technical limitations and potential solutions for further developments
Conclusions
References
Chapter 10: Fluorescent probes for microscopy visualization of cholesterol topography and dynamics in membranes
Abstract
Acknowledgments
Author contributions
Declaration of interests
Introduction
The elusive ideal probe
Cholesterol probes
Indirect cholesterol probes
Direct imaging of intrinsic fluorescent cholesterol analogs
Concluding remarks
References
Chapter 11: Cholesterol transport in blood, lipoproteins, and cholesterol metabolism
Abstract
Author contributions
Introduction
Lipoproteins an overview
Low-density lipoprotein cholesterol
High-density lipoprotein cholesterol
How does aging impact cholesterol metabolism?
Obesity and aging: Two sides of the same coin?
Using mathematical modeling to explore cholesterol metabolism
Discussion of future perspectives
References
Chapter 12: Common laboratory research methods for detection and quantification of cholesterol
Abstract
Introduction to cholesterol detection and quantification
The early era of cholesterol detection and quantification: Colorimetric approaches
MS-based approaches
Imaging-based approaches
Enzymatic methods
Summary and concluding remarks
References
Chapter 13: Approaches for modifying cellular cholesterol levels and their application to mechanistic studies: Examples from the ion channel field
Abstract
Introduction
In vitro methods for modifying cholesterol levels in cell membranes
In vivo modification of cholesterol levels
Applications to mechanistic studies on the effect of cholesterol on ion channel targets
Outlook
References
Section 2: Cholesterol homeostasis and its disruption
Chapter 14: Diet-induced hypercholesterolemia in small laboratory animal models
Abstract
Introduction
Mouse models
Rat models
Hamsters
Guinea pigs
Rabbits
Additional diet considerations
Control diets
References
Chapter 15: Nutrition and cholesterol metabolism
Abstract
Acknowledgments
Introduction
Cholesterol structure
Nutritional recommendations for maintaining healthy blood cholesterol levels
Dietary cholesterol intake
Saturated fat intake
Cholesterol functions
Digestion and absorption of cholesterol
Transport of cholesterol
Endogenous cholesterol synthesis
Blood cholesterol and atherosclerosis
Guinea pigs as a preclinical model
Advances in cholesterol research
Explanatory and predictive models approach
Conclusions
References
Chapter 16: Cholesterol and early development
Abstract
Introduction
The fetus and cholesterol
Steroid hormones in reproduction and early life
Extraembryonic structures, secondary yolk sac and placenta, and materno-fetal cholesterol transport
Maternal cholesterol levels in healthy pregnancies, maternal hyper- and hypocholesterolemia, and consequences for the fetus
Effect of selected medicines related to cholesterol metabolism on the fetal development
Summary
References
Chapter 17: Clinical and biochemical diagnostic methods: What do blood lipid levels tell us?
Abstract
Introduction
Use of conventional laboratory methods to measure lipoproteins by determining their cholesterol content
Beyond standard lipid profiles: Determination of atherogenic lipoproteins by advanced lipoprotein testing
Fasting versus nonfasting lipid measurements
Lipid and lipoprotein testing in laboratory animals
What do lipid/lipoprotein levels tell us?
References
Chapter 18: Familial hypobetalipoproteinemia and abetalipoproteinemia
Abstract
Introduction
ApoB gene mutations causing familial hypobetalipoproteinemia
Familial hypobetalipoproteinemia (FHBL) and coronary heart disease (CHD)
FHBL and hepatic steatosis
FHBL and insulin sensitivity
FHBL, hepatic cirrhosis, and hepatocarcinoma
FHBL and psychiatric disease
Heterozygous FHBL and neurological manifestations
Proprotein convertase subtilisin kexin 9 gene (PCSK9) mutations
Familial combined hypolipidemia (FHBL2)
ANGPTL3 S17X
Abetalipoproteinemia (ABL) and homozygous hypobetalipoproteinemia (HHBL)
Diagnosis and management
Heterozygous FHBL
Pregnancy management
Conclusion
References
Chapter 19: Critical illness and cholesterol levels
Abstract
Acknowledgments
Introduction
Clinical implications of hypocholesterolemia
References
Chapter 20: Familial hypercholesterolemia
Abstract
Introduction
Genetic and molecular background of FH
Familial hypercholesterolemia diagnosis
Familial hypercholesterolemia treatments
Nutrition and familial hypercholesterolemia
Management of homozygous familial hypercholesterolemia
Familial hypercholesterolemia-related diseases
Familial hypercholesterolemia current status and future perspectives
References
Chapter 21: Niemann-Pick type C disease (NPC)
Abstract
Acknowledgment
Introduction
Clinical picture of NPC disease
Genetic background of NPC
Biochemical aspects of NPC1 and NPC2 proteins
Pathomechanisms underlying NPC disease
Diagnostics
Treatment
References
Chapter 22: Rare monogenic disorders of cholesterol metabolism
Abstract
Introduction
Monogenic hypercholesterolemia
Sterol storage diseases
Bile acid biosynthesis disorders
Hypocholesterolemia
References
Chapter 23: Secondary (acquired) hypercholesterolemia
Abstract
Introduction
Causes of secondary hyperlipidemias and their treatment
Conclusions
References
Chapter 24: Blood lipids and molecular pathways of atherogenesis
Abstract
Introduction
Cholesterol metabolism
Pathophysiology of atherosclerosis
Low-density lipoprotein cholesterol and cardiovascular disease
Oxidized low-density lipoprotein cholesterol and cardiovascular disease
High-density lipoprotein cholesterol: Marker or risk factor?
Triglycerides and cardiovascular disease
Genetics and dyslipidemia
Conclusions
References
Chapter 25: Lysosomal acid lipase: Roles in rare deficiency diseases, myeloid cell biology, innate immunity, and common neutral lipid diseases
Abstract
Historical background: Lysosomal acid lipase (LAL)
Structure, properties, and biology of LAL
LAL roles in disease states
Molecular biology and genetics
LAL in diseases beyond the LALDs
References
Further reading
Chapter 26: Cholesterol and pathogens
Abstract
Acknowledgments
Introduction
The role of cholesterol-rich membrane microdomains in infectious diseases
Cholesterol recruitment to pathogen-containing vacuoles
Targeting cellular cholesterol metabolism
Systemic cholesterol levels and pathogens
Cholesterol-lowering agents as potential therapeutics in infectious diseases
Cholesterol and immune response
Summary
References
Chapter 27: Involvement of cholesterol and β-amyloid in the initiation and progression of Alzheimer’s disease
Abstract
Neurodegenerative diseases are a significant health problem: Alzheimer’s disease (AD)
The amyloid cascade as a central cause for Alzheimer’s disease
Cellular domains important for the formation of Aβ and cholesterol
Interactions of Aβ with the neuronal membrane and the initiation of synaptic failure
Participation of membrane lipids in the initiation of Aβ-mediated neurotoxicity
How Aβ and cholesterol might lead to neurodegeneration
Cholesterol affects a number of membrane proteins that fine tune neuronal excitability
The ε4 isoform (ApoE4) factor in disease onset and progression
References
Chapter 28: Cholesterol and alcohol
Abstract
Introduction
Alcohol pharmacology
Alcohol use disorder
Alcohol and cholesterol interactions
Alcohol and lipoproteins
Alcohol and PCSK9
Fetal alcohol spectrum disorders (FASDs) and cholesterol
Targeting lipids for treatment of alcohol-related diseases
Conclusion
References
Section 3: Pharmacological considerations and perspectives
Chapter 29: Cholesterol stiffening of lipid membranes and drug interactions: Insights from neutron spin echo and deuterium NMR spectroscopy
Abstract
Acknowledgment
Introduction
Neutron spin echo spectroscopy of lipid membranes
Solid-state 2H NMR spectroscopy of lipid membranes
Membrane stiffening effect of cholesterol from molecular dynamics simulations
Cholesterol effects on drug uptake and drug delivery applications
Conclusions
References
Chapter 30: Cholesterol in drug delivery systems
Abstract
Introduction
The common synthesis chemistry of modifying cholesterol into the polymers
Cholesterol in the form of drug delivery vehicles
Conclusion
References
Chapter 31: Modification of vascular receptor pharmacology by cholesterol: From molecular determinants to impact on arterial function
Abstract
Introduction
Cholesterol modulation of vasoactive drug action in which the underlying pharmacodynamic process(es) is not fully determined
Cholesterol modulation of vasoactive drug action occurring at the cell membrane where the vasoactive drug receptor of interest is embedded
Cholesterol modulation of vasoactive drug action occurring at the vasoactive drug receptor protein itself
Conclusions and prospective
References
Chapter 32: Clinical strategies for reducing cholesterol levels
Abstract
Introduction
Epidemiology
Major guidelines for lipid-lowering therapy in the United States
Pharmacologic treatment of lipids
Other lipid-lowering therapies
Nonprescription and dietary supplements
Patient education
Clinical pearls
Screening for lipid disorders
Summary
References
General patient education resources for understanding cholesterol disorders and treatment options
Clinician tools
Chapter 33: Medicinal chemistry and pharmacology of statins
Abstract
Introduction
Medicinal chemistry of statins
Pharmacology
Future drugs and concluding remarks
References
Chapter 34: Cyclodextrins as promising therapeutics against cholesterol overload
Abstract
Acknowledgments
Introduction
Cyclodextrins in general
Cyclodextrins in the treatment of Niemann-Pick type C disease
Cyclodextrins with great potential in the treatment of neurodegenerative diseases
Cyclodextrins as promising therapeutics in atherosclerosis
Role of cyclodextrins in the treatment of kidney diseases
Role of cyclodextrins in the treatment of eye disorders
Potential effects of cyclodextrins against coronavirus
Concluding remarks
References
Chapter 35: Hyperlipidemia and rheumatoid arthritis
Abstract
Introduction
Pathophysiologic mechanisms in rheumatoid arthritis (RA)
Articular and extra-articular manifestations of RA
Rheumatoid arthritis treatment
Comorbidities in RA
CVD: A major comorbidity in RA
CVD risk assessment in RA
CVD and atherosclerosis in RA
Lipid profile in RA patients
Mechanisms related to dyslipidemia in RA
Lipid concentration and inflammatory markers
Atherosclerosis and inflammation
Lipid metabolism and inflammation
The impact of cytokines on LDL
Lipid peroxidation
Altered HDL function and structure
Effects of antirheumatic therapy on serum lipid levels
Glucocorticoids (GCs)
DMARDs
Antitumor necrosis factor-alpha (anti-TNF-a) agents
Anti-interleukin-6 (IL-6) agents
Janus kinase inhibitors (JAK inhibitors)
Other agents
Mediterranean diet and RA
The role of exercise in RA
Conclusions
References
Chapter 36: Management of hypercholesterolemia in individuals living with HIV/AIDS
Abstract
Introduction
Nucleoside reverse transcriptase inhibitors (NRTIs)
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Diabetes mellitus, metabolic syndrome and HIV
Conclusion
References
Index

About the Editors

Anna Bukiya
Dr. Anna Bukiya’s PhD laboratory focuses on lipid modulation of ion channel function in excitable tissues and sensitivity to drugs. Dr. Bukiya’s work has been consistently funded by the NIH and private foundations, and she has published 43 original research articles, authored or co-authored 10 reviews, and 9 book chapters. Dr. Bukiya also co-edited two books and served as a sole editor on one book, all focused on the role of lipids in modulating protein function during normal physiology and pathological conditions. The Bukiya laboratory utilizes computational modelling of cholesterol-protein interactions, biochemical and fluorescence microscopy-based quantification of cellular cholesterol levels, rat models of high-cholesterol diet, and statin use to control cholesterol levels in vivo. Dr. Bukiya is a current member of several societies, including Biophysical Society, International Drug Abuse Research Society, and American Society for Pharmacology and Experimental Therapeutics.

Affiliations and Expertise
Professor, Department of Pharmacology, Addiction Science and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA

Alex Dopico
Dr. Alex Dopico MD, PhD received his M.D. from the University of Buenos Aires, specializing in arterial hypertension. Following his Ph.D. in Pharmacology, he conducted postdoctoral training at UMass Worcester focusing on the regulation of ion channels by lipids and alcohols. Over two decades, the Dopico laboratory has addressed ion channel regulation by a wide variety of lipids, including fatty acids, leukotrienes, glycerophospholipids, PIP2 and related phosphoinositides, bile acids and other cholanes, pregnenolone and cholesterol itself. His studies on alcohol and toluene aim at determining the relative contribution of ion channels and their surrounding membrane lipids to drug action, addressing the impact of drug action on organ function, with a focus on cerebral arteries. In 2009, he received a Merit Award from NIAAA for his work on ethanol actions on slo1 channels. He is member of the National Advisory Committee on Alcohol Abuse & Alcoholism.

Affiliations and Expertise
Van Vleet Chair of Excellence, Dept. Pharmacology, Addiction Science and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA