DOCSLIB.ORG

An Examination of Oxysterol Effects on Membrane Bilayers Using Molecular Dynamics Simulations Brett Olsen Washington University in St

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
An Examination of Oxysterol Effects on Membrane Bilayers Using Molecular Dynamics Simulations Brett Olsen Washington University in St Washington University in St. Louis Washington University Open Scholarship All Theses and Dissertations (ETDs) January 2010 An Examination of Oxysterol Effects on Membrane Bilayers Using Molecular Dynamics Simulations Brett Olsen Washington University in St. Louis Follow this and additional works at: https://openscholarship.wustl.edu/etd Recommended Citation Olsen, Brett, "An Examination of Oxysterol Effects on Membrane Bilayers Using Molecular Dynamics Simulations" (2010). All Theses and Dissertations (ETDs). 420. https://openscholarship.wustl.edu/etd/420 This Dissertation is brought to you for free and open access by Washington University Open Scholarship. It has been accepted for inclusion in All Theses and Dissertations (ETDs) by an authorized administrator of Washington University Open Scholarship. For more information, please contact [email protected]. Washington University in Saint Louis Division of Biology and Biological Sciences Program in Molecular and Cellular Biology Dissertation Examination Committee: Nathan Baker, Chair Douglas Covey Katherine Henzler-Wildman Garland Marshall Daniel Ory Paul Schlesinger An Examination of Oxysterol Effects on Membrane Bilayers Using Molecular Dynamics Simulations by Brett Neil Olsen A dissertation presented to the Graduate School of Arts and Sciences of Washington University in partial fulfillment of the requirements for the degree of Doctor of Philosophy August 2010 Saint Louis, Missouri Acknowledgments I would like to thank my doctoral adviser Nathan Baker, whose guidance and advice has been essential to my development as an independent researcher, and whose confidence in my abilities has often surpassed my own. Thanks to my experimental collaborators at Washington University: Paul Schlesinger, Daniel Ory, and Doug Covey, without whom this work never would have been begun. Many thanks to the past and present members of my thesis committee: Nathan Baker, Paul Schlesinger, Daniel Ory, David Sept, Lev Gelb, Doug Covey, Garland Marshall, and Katherine Henzler-Wildman, for their direction and criticism. Thanks to the multitude of other scientific colleagues who have offered contributions to and criticisms of this work in private discussions: Michael Bradley, Rachel Rice, Sunjoo Lee, Albert Mao, Marc Sherman, Peter Jones, Diana Wong, and others too numerous to mention. Thanks to the Texas Advanced Computing Center, which generously provided supercomputer time on which most of these simulations were run and to Malcolm Tobias, who has been instrumental in keeping the computational resources needed for this work up and running. Thanks to Leslie Lamport and Donald Knuth for LATEX and TEX, without which I would have had much less fun formatting my thesis. Thanks to my friends and family who kept me sane through the course of my doctoral work: my parents Reed and Lorraine Olsen, my brother Cullam and my sister Janel, and my friends Robin and Salomon Trujillo, Jon and Andrea Hunt, Daniel and Lena Koslover, Joe and Tina Wasem, Mike and Erin Connor, Tom and Sarah Pierce, Rebecca Craig-Shapiro, Albert Mao, Adam Greenbaum, Peter and Sarah Freddolino, and Robert Kern. This work is dedicated to my wife Clare. You have been in my life for nine years, and you have brought nothing but joy, happiness, and love into it. You have borne with my eccentricities with a smile and a kiss, you have been with me to laugh in happy times and comfort in sad. I picked up and started a new life to be with you, and every day I am grateful that I made the right decision. Thank you. ii Contents 1 Background and Introduction 1 1.1 Biomembranes . 1 1.1.1 Phospholipid Bilayers . 1 1.1.2 Membrane Composition and Regulation . 3 1.2 Sterols . 4 1.2.1 Sterol Structure . 5 1.2.2 Cholesterol . 6 1.2.3 Oxysterols . 7 1.2.4 Cholesterol Regulation . 8 2 Examination of Oxysterol Membrane Effects 10 2.1 Introduction . 10 2.2 Methods . 13 2.2.1 Parameters and Structures . 13 2.2.2 Simulations . 15 2.2.3 Analytical Methods . 15 2.3 Results . 16 2.3.1 Equilibration . 16 2.3.2 Areas and Volumes . 17 2.3.3 Densities . 21 2.3.4 Membrane Mechanical Properties . 22 2.3.5 Lipid Structure . 25 2.3.6 Sterol Orientation and Organization . 27 2.4 Discussion . 32 iii 2.5 Conclusions . 35 3 Interactions Between 25-Hydroxycholesterol and Cholesterol in POPC Bilayers 37 3.1 Introduction . 38 3.2 Methods . 39 3.2.1 Parameters and Structures . 39 3.2.2 Simulations . 40 3.2.3 Analysis Methods . 41 3.3 Results . 44 3.3.1 Equilibration . 44 3.3.2 Membrane Effects . 44 3.3.3 Molecular Effects . 49 3.4 Discussion . 56 4 Influence of Phospholipid Acyl Chains on 25-Hydroxycholesterol Membrane Interactions 59 4.1 Introduction . 60 4.2 Methods . 61 4.2.1 Parameters and Structures . 61 4.2.2 Simulations . 63 4.3 Results . 64 4.3.1 Membrane Effects . 64 4.3.2 Lipid Effects . 70 4.4 Discussion . 74 5 Conclusions 78 5.1 Summary of Simulations . 78 5.2 Mechanisms of Oxysterol Signaling . 81 5.3 Future Work . 82 6 Appendix 84 6.1 Supporting Information, Chapter 2 . 84 6.1.1 Statistical Inefficiency . 84 6.1.2 Kolmogorov-Smirnov Test . 85 6.1.3 Equilibration . 85 iv 6.1.4 Membrane System Construction . 86 6.1.5 Radial Distribution Functions . 87 6.1.6 Bilayer Structural Properties . 87 6.1.7 Sterol Parameters . 90 v List of Figures 1.1 Lipid assemblies. 2 1.2 Glycerophospholipid structure. 2 1.3 Sterol structures. 5 2.1 Cholesterol and 25-hydroxycholesterol structures. 12 2.2 Membrane areas over time. 16 2.3 Membrane SASA components. 19 2.4 Membrane volume distributions. 20 2.5 Bilayer density profiles. 21 2.6 Bulk POPC membrane properties. 24 2.7 POPC tail order parameters. 26 2.8 Sterol hydroxyl hydrogen bonding. 26 2.9 Demonstration of Euler angles. 28 2.10 Distributions of cholesterol orientation. 30 2.11 Distributions of 25-hydroxycholesterol orientation. 31 2.12 Representative cholesterols. 32 2.13 Representative 25-hydroxycholesterols. 33 3.1 Mixed sterol membrane area distributions. 45 3.2 Mixed sterol SASA contributions. 47 3.3 Mixed sterol bilayer mass density profiles. 49 3.4 Cholesterol SASA distributions. ..
Load more

Recommended publications
  • Neurosteroids and Brain Sterols
    NEUROSTEROIDS AND BRAIN STEROLS Lathe, R. and Seckl, J.R. To appear in: Mason, J.I. (ed.) Genetics of Steroid Biosynthesis and Function. Modern Genetics, volume 6, Harwood Academic, Amsterdam. in press (2002). Now published as Lathe, R., and Seckl, J.R. (2002). Neurosteroids and brain sterols. In: Mason, J.I. (ed.) Genetics of Steroid Biosynthesis and Function. Modern Genetics, volume 6, Harwood Academic, Amsterdam. pp 405-472. File:-//integra/t&f/Gsb/3b2/Gsbc15.3d ± Date:-19.12.2001 ± Time:-4:23pm 15.NEUROSTEROIDSANDBRAINSTEROLS RICHARD LATHE*,y AND JONATHAN R. SECKL* *Centre for Genome Research and Molecular Medicine Centre, Centre for Neuroscience, The University of Edinburgh, King's Buildings, Edinburgh EH93JQ , UK Conventionally, steroids operate via transcription, but a subclass of brain-active steroids, dubbed neurosteroids, may govern cognitive processes via membrane-associated receptors. De novo synthesis of neurosteroids within the brain has been discussed; we suggest that these may derive primarily from the circulation. In contrast, the brain is largely self-sufficient in cholesterol. Synthesis and metabolism of cholesterol and its oxysterol derivatives appears to be crucial to brain development and function, emphasized by drugs (anti-convulsants, neuroleptics)and mutations (Smith-Lemli-Opitz, Niemann-Pick disease type C, cerebrotendinous xanthamatosis)that affect these pathways and have marked brain effects. Receptors for steroids and sterols are discussed, particularly those at cell-surface and intracellular membranes including sites of sterol metabolism and trafficking (including sigma-1, the emopamil binding protein [EBP], and the peripheral benzodiazepine receptor [PBR]). Potential overlaps between sterol and steroid signaling are discussed. In addition to regulating neuronal activity, we suggest that steroids and sterols may regulate proliferative and degenerative processes in the brain including apoptosis induction.
    [Show full text]
  • Cholesterol Metabolites 25-Hydroxycholesterol and 25-Hydroxycholesterol 3-Sulfate Are Potent Paired Regulators: from Discovery to Clinical Usage
    H OH metabolites OH Review Cholesterol Metabolites 25-Hydroxycholesterol and 25-Hydroxycholesterol 3-Sulfate Are Potent Paired Regulators: From Discovery to Clinical Usage Yaping Wang 1, Xiaobo Li 2 and Shunlin Ren 1,* 1 Department of Internal Medicine, McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23249, USA; [email protected] 2 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; [email protected] * Correspondence: [email protected]; Tel.: +1-(804)-675-5000 (ext. 4973) Abstract: Oxysterols have long been believed to be ligands of nuclear receptors such as liver × recep- tor (LXR), and they play an important role in lipid homeostasis and in the immune system, where they are involved in both transcriptional and posttranscriptional mechanisms. However, they are increas- ingly associated with a wide variety of other, sometimes surprising, cell functions. Oxysterols have also been implicated in several diseases such as metabolic syndrome. Oxysterols can be sulfated, and the sulfated oxysterols act in different directions: they decrease lipid biosynthesis, suppress inflammatory responses, and promote cell survival. Our recent reports have shown that oxysterol and oxysterol sulfates are paired epigenetic regulators, agonists, and antagonists of DNA methyl- transferases, indicating that their function of global regulation is through epigenetic modification. In this review, we explore our latest research of 25-hydroxycholesterol and 25-hydroxycholesterol 3-sulfate in a novel regulatory mechanism and evaluate the current evidence for these roles. Citation: Wang, Y.; Li, X.; Ren, S. Keywords: oxysterol sulfates; oxysterol sulfation; epigenetic regulators; 25-hydroxysterol; Cholesterol Metabolites 25-hydroxycholesterol 3-sulfate; 25-hydroxycholesterol 3,25-disulfate 25-Hydroxycholesterol and 25-Hydroxycholesterol 3-Sulfate Are Potent Paired Regulators: From Discovery to Clinical Usage.
    [Show full text]
  • Cholesterol Metabolites Exported from Human Brain
    Steroids xxx (2015) xxx–xxx Contents lists available at ScienceDirect Steroids journal homepage: www.elsevier.com/locate/steroids Cholesterol metabolites exported from human brain Luigi Iuliano a, Peter J. Crick b,1, Chiara Zerbinati a, Luigi Tritapepe c, Jonas Abdel-Khalik b, Marc Poirot d, ⇑ ⇑ Yuqin Wang b, , William J. Griffiths b, a Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, corso della Repubblica 79, Latina 04100, Italy b College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK c Department of Anesthesiology and Intensive Care, Sapienza University of Rome, vial del Policlinico 163, Rome 00161, Italy d UMR 1037 INSERM-University Toulouse III, Cancer Research Center of Toulouse, and Institut Claudius Regaud, 31052 Toulouse, France article info abstract Article history: The human brain contains approximately 25% of the body’s cholesterol. The brain is separated from the Received 16 December 2014 circulation by the blood brain barrier. While cholesterol will not passes this barrier, oxygenated forms of Received in revised form 13 January 2015 cholesterol can cross the barrier. Here by measuring the difference in the oxysterol content of blood Accepted 23 January 2015 plasma in the jugular vein and in a forearm vein by mass spectrometry (MS) we were able to determine Available online xxxx the flux of more than 20 cholesterol metabolites between brain and the circulation. We confirm that 24S- hydroxycholesterol is exported from brain at a rate of about 2–3 mg/24 h. Gas chromatography (GC)–MS Keywords: data shows that the cholesterol metabolites 5a-hydroxy-6-oxocholesterol (3b,5a-dihydroxycholestan-6- Oxysterol one), 7b-hydroxycholesterol and 7-oxocholesterol, generally considered to be formed through reactive LC–MS GC–MS oxygen species, are similarly exported from brain at rates of about 0.1, 2 and 2 mg/24 h, respectively.
    [Show full text]
  • Do Oxysterols Control Cholesterol Homeostasis?
    Do oxysterols control cholesterol homeostasis? Ingemar Björkhem J Clin Invest. 2002;110(6):725-730. https://doi.org/10.1172/JCI16388. Perspective Oxysterols are oxygenated derivatives of cholesterol with a very short half-life relative to cholesterol. As a consequence they are present in very low concentrations in all mammalian systems, almost invariably accompanied by 103- to 106-fold excess of cholesterol. Oxysterols are important intermediates in a number of hepatic and extrahepatic catabolic pathways, most of which generate water-soluble bile acids as final products. Based on largely indirect evidence, and in spite of their low levels in vivo, oxysterols are generally believed to be important physiological mediators of cholesterol- induced effects. Perhaps the best support for this model is the existence of nuclear receptors that bind these compounds with high affinity and the fact that oxysterols potently regulate the expression of sterol-sensitive genes in vitro. Here I consider the role of oxysterols as intermediates in different catabolic pathways, and I weigh the evidence for and against the “oxysterol hypothesis” of cholesterol homeostasis. Oxygenation in cholesterol metabolism Cholesterol synthesis requires only one oxygenation reaction, but several such steps are necessary in its degradation to bile acids and its conversion to steroid hormones. Introduction of an oxygen atom in cholesterol drastically reduces its half-life and directs the molecule to leave the body. The physical properties of oxysterols facilitate their degradation and excretion, as oxysterols are able to pass lipophilic membranes much more quickly than does cholesterol […] Find the latest version: https://jci.me/16388/pdf PERSPECTIVE Biology and biochemistry of cholesterol | Ira Tabas, Series Editor Do oxysterols control cholesterol homeostasis? Ingemar Björkhem Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden J.
    [Show full text]
  • C1orf32 Fused to the Fc Fragment for the Treatment of Multiple Sclerosis, Rheumatoid Arthritis and Other Autoimmune Disorders
    (19) TZZ¥ Z _ T (11) EP 3 202 415 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 09.08.2017 Bulletin 2017/32 A61K 38/17 (2006.01) A61P 25/28 (2006.01) (21) Application number: 17161149.4 (22) Date of filing: 30.06.2011 (84) Designated Contracting States: • ROTMAN, Galit AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 46725 Herzliya (IL) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • LEVINE, Zurit PL PT RO RS SE SI SK SM TR 46725 Herzliya (IL) • MILLER, Stephen D. (30) Priority: 30.06.2010 US 360011 P Chicago, IL Illinois 60611 (US) • PODOJIL, Joseph R. (62) Document number(s) of the earlier application(s) in Chicago, IL Illinois 60611 (US) accordance with Art. 76 EPC: 11748719.9 / 2 588 123 (74) Representative: Fuchs Patentanwälte Partnerschaft mbB (71) Applicant: Compugen Ltd. Westhafenplatz 1 5885849 Holon (IL) 60327 Frankfurt am Main (DE) (72) Inventors: Remarks: • HECHT, Iris This application was filed on 15-03-2017 as a Tel Aviv (IL) divisional application to the application mentioned under INID code 62. (54) C1ORF32 FUSED TO THE FC FRAGMENT FOR THE TREATMENT OF MULTIPLE SCLEROSIS, RHEUMATOID ARTHRITIS AND OTHER AUTOIMMUNE DISORDERS (57) This invention relates to a protein C1ORF32 and development, including but not limited to as immune its variants and fragments and fusion proteins thereof, modulatorsand for immunetherapy, including for autoim- and methods of use therof for immunotherapy, and drug mune disorders. EP 3 202 415 A2 Printed by Jouve, 75001 PARIS (FR) EP 3 202 415 A2 Description FIELD OF THE INVENTION 5 [0001] This invention relates to a novel protein, and its variants, fragments and fusion proteins thereof, and methods of use therof for immunotherapy, and drug development.
    [Show full text]
  • The Role of Autophagy in Survival Response Induced by 27- T Hydroxycholesterol in Human Promonocytic Cells
    Redox Biology 17 (2018) 400–410 Contents lists available at ScienceDirect Redox Biology journal homepage: www.elsevier.com/locate/redox Research Paper The role of autophagy in survival response induced by 27- T hydroxycholesterol in human promonocytic cells Beyza Vurusanera, Simona Gargiulob, Gabriella Testab, Paola Gambab, Gabriella Leonarduzzib, ⁎ Giuseppe Polib, Huveyda Basagaa, a Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey b Department of Clinical and Biological Sciences, University of Torino, Torino, Italy ARTICLE INFO ABSTRACT Keywords: Autophagy has been shown to be stimulated in advanced atherosclerotic plaques by metabolic stress, in- Oxysterols flammation and oxidized lipids. The lack of published studies addressing the potential stimulation of pro-sur- 27-hydroxycholesterol vival autophagy by oxysterols, a family of cholesterol oxidation products, has prompted our study. Thus, the goal Autophagy of the current study is to elucidate the molecular mechanism of the autophagy induced by 27-hydroxycholesterol ROS (27-OH), that is one of the most abundant oxysterols in advanced atherosclerotic lesions, and to assess whether Survival signaling the pro-oxidant effect of the oxysterol is involved in the given response. Here we showed that 27-OH, in a low micromolar range, activates a pro-survival autophagic response in terms of increased LC3 II/LC3 I ratio and Beclin 1, that depends on the up-regulation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt pathways as a potential result of an intracellular reactive oxygen species increase provoked by the oxysterol in human promonocytic U937 cells. Moreover, 27-OH induced autophagy is dependent on the relation between nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant response and p62.
    [Show full text]
  • Smith-Lemli-Opitz Syndrome and Inborn Errors of Cholesterol Synthesis
    BRIEF REPORT Smith-Lemli-Opitz syndrome and inborn errors of cholesterol synthesis: summary of the 2007 SLO/RSH Foundation scientific conference sponsored by the National Institutes of Health Louise S. Merkens, PhD1, Christopher Wassif, MS2, Kristy Healy, RN, CCRC1, Anuradha S. Pappu, PhD3, Andrea E. DeBarber, PhD3, Jennifer A. Penfield, MS, PA-C1, Rebecca A. Lindsay, BA4, Jean-Baptiste Roullet, PhD1, Forbes D. Porter, MD, PhD2, and Robert D. Steiner, MD1,5 Abstract: In June 2007, the Smith-Lemli-Opitz/RSH Foundation held a tive research projects that would ultimately improve our under- scientific conference hosted jointly by Dr. Robert Steiner from Oregon standing and treatment of SLOS and other inborn errors of Health & Science University and Dr. Forbes D. Porter from The Eunice cholesterol synthesis. Kennedy Shriver National Institute for Child Health and Human De- Several of the scientists also participated in the concurrent velopment, National Institutes of Health. The main goal of this meeting Smith-Lemli-Opitz/RSH Foundation family conference. These was to promote interaction between scientists with expertise in choles- family sessions occur every 2 years as a forum for education of terol homeostasis, brain cholesterol metabolism, developmental biol- families with affected children about SLOS and dealing with ogy, and oxysterol and neurosteroid biochemistry, clinicians research- children with a chronic disease. They are also an opportunity for ing and treating patients with Smith-Lemli-Opitz syndrome, the patient SLOS families to meet and network. The families were invited support organization and families. This report summarizes the presen- to ask questions and express concerns to a panel of physicians, tations and discussions at the conference, represents the conference psychologists, dietitians, and scientists currently working in the proceedings, and is intended to foster collaborative research and ulti- diagnosis and management of patients with SLOS.
    [Show full text]
  • A Comparison of the Potential Unfavorable Effects Of
    Biosci. Biotechnol. Biochem., 72 (12), 3128–3133, 2008 A Comparison of the Potential Unfavorable Effects of Oxycholesterol and Oxyphytosterol in Mice: Different Effects, on Cerebral 24S-Hydroxychoelsterol and Serum Triacylglycerols Levels y Hyun-jung BANG, Chiyo ARAKAWA, Michihiro TAKADA, Masao SATO, and Katsumi IMAIZUMI Laboratory of Nutrition Chemistry, Division of Bioresource and Bioenvironmental Sciences, Graduate School, Kyushu University, Fukuoka 812-8581, Japan Received April 16, 2008; Accepted August 9, 2008; Online Publication, December 7, 2008 [doi:10.1271/bbb.80256] Sterol oxidation products derived from cholesterol Our previous study indicated that oxidation products and phytosterol are formed during the processing and derived from cholesterol and plant sterols accumulated storage of foods. The objective of the present study was to a considerable extent in the tissues of apolipopro- to assess the potential unfavorable effects of oxysterols tein E deficient mice, but the atherosclerotic severity in in mice. C57BL/6J mice were fed an AIN-93G-based the aortic value of the mice fed the oxysterols was not diet containing 0.2 g/kg of oxycholesterol or oxyphyto- different from that in the oxysterol-free group.7,8) Our sterol for 4 weeks. The most abundant oxysterol in the findings are different from those showing a role of diet was 7-ketosterol, but -epoxycholesterol, -epox- dietary oxycholesterols in the development of athero- ycholesterol, or 7 -hydroxyphytosterol, and 7 -hydro- sclerosis in experimental animals.10,11) Very few data xyphytosterol were more prominent than 7-ketosterol in except those from Tomoyori et al.8) are available on the the serum and liver respectively.
    [Show full text]
  • Diverse Immunoregulatory Roles of Oxysterols— the Oxidized Cholesterol Metabolites
    H OH metabolites OH Review Diverse Immunoregulatory Roles of Oxysterols— The Oxidized Cholesterol Metabolites Chloe Choi 1,* and David K. Finlay 1,2,* 1 School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Pearse Street 152-160, Dublin 2, Ireland 2 School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Pearse Street 152-160, Dublin 2, Ireland * Correspondence: [email protected] (C.C.); fi[email protected] (D.K.F.); Tel.: +353-1-896-3564 (D.K.F.) Received: 13 August 2020; Accepted: 24 September 2020; Published: 28 September 2020 Abstract: Intermediates of both cholesterol synthesis and cholesterol metabolism can have diverse roles in the control of cellular processes that go beyond the control of cholesterol homeostasis. For example, oxidized forms of cholesterol, called oxysterols have functions ranging from the control of gene expression, signal transduction and cell migration. This is of particular interest in the context of immunology and immunometabolism where we now know that metabolic processes are key towards shaping the nature of immune responses. Equally, aberrant metabolic processes including altered cholesterol homeostasis contribute to immune dysregulation and dysfunction in pathological situations. This review article brings together our current understanding of how oxysterols affect the control of immune responses in diverse immunological settings. Keywords: oxysterols; cholesterol; SREBP; LXR; GPR183; ROR; SERM; Ch25h; Cyp27a1; inflammation; cancer; infection; obesity; autoimmunity; endometriosis; immunometabolism 1. Introduction Cholesterol is a vital component of our cells and our bodies. It is a structural component of cellular membranes, plays a role in regulating intracellular signal transduction and is a precursor for the generation of other important molecules such as bile acids and steroid hormones.
    [Show full text]
  • Deleterious Effects of Food Habits in Present Era Aliya Siddiqui1*And Naga Anusha P2 1Department of Biotechnology, Chaitanya P.G
    erg All y & of T l h a e n r r a Siddiqui and Anusha. J Aller Ther 2012, 3:1 p u y o J Journal of Allergy & Therapy DOI: 10.4172/2155-6121.1000114 ISSN: 2155-6121 Review Article Open Access Deleterious Effects of Food Habits in Present Era Aliya Siddiqui1*and Naga Anusha P2 1Department of Biotechnology, Chaitanya P.G. College, Kakatiya University, India 2 Department of Biotechnology, Sri Y.N. College, Andhra University, India Abstract Food is any substance usually of plant or animal origin consumed to provide nutritional support for the body. It contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals etc. Consuming healthy food like fresh fruits and vegetables gives the body strength and power to stay healthy without any infections and diseases. In spite of knowing the value of healthy food, most of the people prefer fast food which affects their health and lives. This Review Article deals with the Food and its Impact on Human Health, what are the side effects when food is taken in excess amounts and what might happens when it is not supplied to the body in enough quantities, what could be the problems which most of the people face if fast food or junk food is consumed in large or excess quantities. As fast food culture is an emerging trend among the younger generation and most of them may suffer with food allergies and various health problems when consumed on a regular basis. Fast food has become a prominent feature of the diet for most of the people in United States and increasing, throughout the world.
    [Show full text]
  • Cholesterol Dyshomeostasis and Age Related Macular Degeneration Bhanu Chandar Dasari
    University of North Dakota UND Scholarly Commons Theses and Dissertations Theses, Dissertations, and Senior Projects 1-1-2012 Cholesterol Dyshomeostasis And Age Related Macular Degeneration Bhanu Chandar Dasari Follow this and additional works at: https://commons.und.edu/theses Recommended Citation Dasari, Bhanu Chandar, "Cholesterol Dyshomeostasis And Age Related Macular Degeneration" (2012). Theses and Dissertations. 1235. https://commons.und.edu/theses/1235 This Thesis is brought to you for free and open access by the Theses, Dissertations, and Senior Projects at UND Scholarly Commons. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of UND Scholarly Commons. For more information, please contact [email protected]. CHOLESTEROL DYSHOMEOSTASIS AND AGE RELATED MACULAR DEGENERATION by Bhanu Chandar Dasari Bachelor of Science, Kakatiya University, 1999 Master of Science, University of Pune, 2001 A Dissertation Submitted to the Graduate Faculty of the University of North Dakota in partial fulfillment of the requirements for the degree of Doctor of Philosophy Grand Forks, North Dakota May 2012 This dissertation, submitted by Bhanu Chandar Dasari in partial fulfillment of the requirements for the Degree of Doctor of Philosophy from the University of North Dakota, has been read by the Faculty Advisory Committee under whom the work has been done and is hereby approved. __________________________________ Othman Ghribi, Ph.D. __________________________________ Brij B. Singh, Ph.D. __________________________________ Colin K. Combs, Ph.D. __________________________________ James E. Porter, Ph.D. __________________________________ Saobo Lei, Ph.D. This dissertation is being submitted by the appointed advisory committee as having met all of the requirements of the Graduate School at the University of North Dakota and is hereby approved.
    [Show full text]
  • Method Development for Valid High-Resolution Profiling Of
    Method development for valid high‐resolution profiling of mitochondria and Omics investigation of mitochondrial adaptions to excess energy intake and physical exercise Dissertation der Mathematisch‐Naturwissenschaftlichen Fakultät der Eberhard Karls Universität Tübingen zur Erlangung des Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) vorgelegt von Lisa Claudia Charlotte Kappler aus Weingarten Tübingen 2018 Gedruckt mit Genehmigung der Mathematisch‐Naturwissenschaftlichen Fakultät der Eberhard Karls Universität Tübingen. Tag der mündlichen Qualifikation: 27.03.2018 Dekan: Prof. Dr. Wolfgang Rosenstiel 1. Berichterstatterin: Prof. Dr. Carolin Huhn 2. Berichterstatter: Prof. Dr. Rainer Lehmann Over the long term, symbiosis is more useful than parasitism. More fun, too. Ask any mitochondria. ‐Larry Wall‐ Scopes and aims of the thesis Index 1 SCOPES AND AIMS OF THE THESIS .............................................................................. 1 2 INTRODUCTION ................................................................................................................. 2 2.1 Insulin resistance and type 2 diabetes ................................................................................................. 2 2.1.1 Diet and physical activity ...................................................................................................................... 3 2.2 Mitochondria, structure and function ................................................................................................. 3 2.2.1 Function of
    [Show full text]