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Cholesterol
From Chemistry and Biophysics to the Clinic
- 1st Edition - April 26, 2022
- Editors: Anna N. Bukiya, Alex M. Dopico
- Language: English
- Paperback ISBN:9 7 8 - 0 - 3 2 3 - 8 5 8 5 7 - 1
- eBook ISBN:9 7 8 - 0 - 3 2 3 - 8 5 8 5 8 - 8
With Cholesterol, Drs. Anna Bukiya and Alex Dopico have compiled a comprehensive resource on biological and clinical aspects of cholesterol, spanning biophysics and biochemis… Read more
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Request a sales quoteWith 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.
- Ties basic biology to clinical application and drug discovery
- Provides methods and protocols for lab-based cholesterol research and clinical testing
- Examines the latest pharmacological discoveries employed to tackle cholesterol related disorders
- Includes chapter contributions from a wide range of specialists, uniting various disciplines
- 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
- No. of pages: 1058
- Language: English
- Edition: 1
- Published: April 26, 2022
- Imprint: Academic Press
- Paperback ISBN: 9780323858571
- eBook ISBN: 9780323858588
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Anna N. Bukiya
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