DOCSLIB.ORG

Magnesium Regulation of Glucose and Fatty Acid

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Magnesium Regulation of Glucose and Fatty Acid MAGNESIUM REGULATION OF GLUCOSE AND FATTY ACID METABOLISM IN HEPG2 CELLS By ZIENAB ETWEBI Submitted in partial fulfillment of the requirements For the degree of Master of Science Thesis Advisor: Dr. Andrea Romani Department of Physiology and Biophysics CASE WESTERN RESERVE UNIVERSITY August, 2011 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Zienab Etwebi candidate for the Master of Science degree *. (signed) Dr. William Schilling (chair of the committee) Dr. George Dubyak Dr. Margaret Chandler Dr. John Kirwan Dr. Colleen Croniger Dr. Andrea Romani (date) 05/18/2011 *We also certify that written approval has been obtained for any proprietary material contained therein. Dedication I would like to dedicate this thesis to my very supportive husband, Ghasan Ferjani and my family back home. Without their help, encouragement, and ongoing support I would not be where I am today. Thank you. i Table of Contents Table of Contents…………………………………………………………………….…..ii List of Tables………………………………………………………………………..........iii List of Figures ………………………………………………………………….………...iv Acknowledgement…………………………………………..…………….……………..vi Abbreviations used in the Text………………………………………………………......vii Abstract……………………………..……………..…………………………………......ix Introduction………………………………………………………………………..……..1 Magnesium Distribution…………………………………………………………………..2 Magnesium transport and hormonal regulation………..………………………………….4 Magnesium and cell metabolism……………………………………..………………….10 Research Objective and Specific Aims…………………………….…………….………24 Materials and Methods………………………………………………………….…….….25 Results……………………………………………………………………………………32 Discussion………………………………………………………………………………..38 Future Directions…………………………………………………………...……………43 Bibliography……………………………………………………………………………..66 ii List of Tables Table 1 A List of Analytical Methods used to Measure Mg2+ Content and Distribution……………………………………………………..………..45 Table 2 Tissues in which a Na+-dependent Mg2+ Efflux has been Observed or Hypothesized.……………………………..……………………………...46 Table 3 Facilitative Glucose Transporter Isoforms…..….……….………….……47 Table 4 Primers for Quantitative Real-Time PCR ………...………....…………..48 iii List of Figures Figure 1 Cellular Magnisium Profile………………………………………...…….49 Figure 2 Magnesium Transport and Hormonal Regulation………………….…….50 Figure 3 Magnesium Compartmentalization…………………………………....…51 Figure 4 Magnesium’s affect on ATP levels…………………………………….…52 Figure 5A Magnesium’s Effect on Glucose Uptake without insulin…………...…....53 Figure 5B Magnesium’s Effect on Glucose Uptake with insulin………………....…53 Figure 6A Insulin’s Effect on Glucose Uptake in 0.8 mM Mg2+ ………………..…..54 Figure 6B Insulin’s Effect on Glucose Uptake in 0.4 mM Mg2+ ………………..….54 Figure 7 Effect of Magnesium on Glucose Transporters (qPCR) ……………......55 Figure 8 Effect of Magnesium on Glucose Transporters (WB) ………………..…56 Figure 9 Effect of Acute [Mg2+]o Change on Glucose Uptake ………………..…57 Figure 10 Effect of Magnesium on SREBP-1c and SREBP2 (qPCR)…………...…58 Figure 11 Effect of Magnesium on SREBP-1c and SREBP2 (WB).…………...…..59 Figure 12 Effect of Magnesium on SCAP and Insig2.…….…………………..…....60 Figure 13A Effect of Magnesium on PPARα ……………………………….....…….61 Figure 13B Effect of Magnesium on PPARγ………………….. …………………….61 Figure 14A Effect of Magnesium on Glucose Transporters in animals (qPCR) …....62 Figure 14B Effect of Magnesium on Glucose Transporters in animals(WB) ….....…62 iv Figure 15 Effect of Magnesium on SREBP-1c in animals (qPCR) …………….…63 Figure 16A Effect of Magnesium on SREBP-1c in SD rats (WB)………………..…64 Figure 16B Effect of Magnesium on SREBP-1c in B6 mice (WB) ………………...64 Figure 17A Effect of Magnesium on PPARα in Animals ……….………………..…65 Figure 17B Effect of Magnesium on PPARγ in Animals ……….………………..…65 v Acknowledgements I would like to extend my appreciation to my thesis advisor Andrea Romani, for he has been very helpful and supportive throughout this process. In addition, I would like to thank my thesis committee members, Dr. Schilling, Dr. Dubyak, Dr. Chandler, Dr. Kirwan, and Dr. Croniger. I would also like to thank the rest of my family for their continued encouragement and support. vi Abbreviations used in the Text AAS atomic absorbance spectrophotometry ANOVA analysis of variance ATP adenosine tri-phosphate cAMP cyclic adenosine monophosphate DAG diacylglycerol 2,3-DPG 2,3-diphosphoglycerate EPXMA electron probe X-ray microanalysis HDL high-density lipoproteins HepG2 human hepatoma cells Insig insulin-induced gene IP3 inositol tri-phosphate LCAT lecithin cholesterol acyltransferase LPL lipoprotein lipase [Mg2+]i intracellular free Mg2+ concentration 2+ 2+ [Mg ]o extracellular Mg concentration PIP2 phosphatidylinositol-4,5-bisphosphate PLC phospholipase C PKC protein kinase C vii PPAR peroxisome proliferator activated receptors R.E.R Rough endoplasmic reticulum SCAP SREBP-cleavage activating protein SD rats Sprague-Dawley rats SREBP sterol regulatory element binding proteins TGRLP triacylglycerol-rich lipoprotein TBS tris-buffered saline TRP transient receptor potential VP vasopressin V1aR vasopressin receptor 1a viii Magnesium Regulation of Glucose and Fatty Acid Metabolism in HEPG2 Cells Abstract By Zienab Etwebi Magnesium (Mg2+) is an important cation for a variety of cell functions such as enzyme activity, nucleic acid and protein synthesis, and energy metabolism. Mg2+ deficiency has been correlated with the onset and progression of several pathological conditions including diabetes, insulin resistance, metabolic syndrome and obesity. Several studies looking at Mg2+ homeostasis show that Mg2+ homeostasis is associated with glucose metabolism and is inversely correlated with lipid metabolism. Exposure to Mg2+ deficient diet results in a noticeable decrease in hepatic glucose accumulation and a two- fold increase in intrahepatic triglyceride content. In this study, we investigated the effect of changes in Mg2+ concentrations inside and/or outside the liver cell on glucose uptake in the absence and in the presence of insulin stimulation. Our results show that low extracellular Mg2+ content impairs insulin stimulated glucose uptake, with no significant effects on glucose transporters expression. In the case of lipid metabolism, low extracellular Mg2+ content or Mg2+ deficiency decreases the levels of SREBP-1c precursor, an insulin dependent transcription factor, further corroborating the involvement of Mg2+ in modulating hepatic response to insulin. Mg2+ deficiency also decreases the expression level of PPARα, a transcriptional factor involved in fatty acid oxidation. Lastly, Mg2+ deficiency upregulates SREBP2, and PPARγ, transcription ix factors that are both involved in increasing fatty acid synthesis in liver cells. All together our data indicate that extracellular and cellular Mg2+ levels are important in modulating glucose uptake and fatty acids metabolism in liver cells. x 1. Introduction Magnesium (Mg2+) is a divalent cation with a relatively small size and a large hydration shell. It is the second most abundant cation within the cell and is essential for a number of cell functions such as the transport of calcium and potassium ions, enzyme activities, nucleic acid and protein synthesis, energy metabolism and cell proliferation (Flatman, 1984 and Grubbs & Maguire 1987). Intracellular regulation of Mg2+ is very important to maintain proper cellular functions such as DNA transcription, oxidative phosphorylation, and glycolysis (Barbagallo et al., 2009; Bogucka et al., 1976). Mg2+ plays a critical role in the regulation of metabolism, hormone response and cell growth in many cell systems. Mg2+ is also a cofactor in a number of intracellular enzymatic processes and in stabilizing membrane integrity (Laires et al., 2004). Research has found that cellular Mg2+ content is maintained below the concentration predicted by the transmembrane electrochemical potential in skeletal, smooth, and cardiac muscle (Flatman, 1984). This is evidence that cellular Mg2+ content is regulated by precise control mechanism(s) at the level of influx, efflux, intracellular compartmentation and buffering (Cole & Quamme, 2000). Although a large body of information on Mg2+ transport has been obtained from bacteria and giant cells, and despite the abundance and importance of cellular Mg2+, limited and often inconsistent data are available in the literature to explain Mg2+ mobilization or Mg2+ intracellular compartmentation in response to external stimuli in mammalian cells. Only in the past few years have some of the transport and regulatory mechanisms been identified, increasing their physiological and pathological significance. 1 Magnesium Distribution Mg2+ is the fourth most abundant cation after Na+, K+ and Ca2+ in the whole body, and the second most abundant after K+ at the cellular level. Mg2+ plays a major role in intracellular and biochemical functions (Cowan, 1995). Total cellular Mg2+ levels range between 14 and 20mM (Grubbs & Maguire, 1987 and Romani & Scarpa, 1992b). These levels were confirmed by Electron Probe X-ray Micro-Analysis (EPXMA), which measures total element content (Na, K, Ca, Mg, P, S and Cl) in whole cells such as hepatocytes (Dalal et al., 1998), smooth muscle cells (Ziegler et al., 1992), cardiac myocytes (Shuman & Somlyo, 1987), skeletal muscles (Somlyo et al., 1985) as well as within distinct cellular organelles. Previous experiments have shown that Mg2+ is highly compartmentalized within the nucleus, endoplasmic reticulum, mitochondria and cytoplasm. In the nucleus and endoplasmic
Load more

Recommended publications
  • Amphibolic Nature of Krebs Cycle
    Amphibolic nature of Krebs Cycle How what we are is what we eat • In aerobic organisms, the citric acid cycle is an amphibolic pathway, one that serves in both catabolic and anabolic processes. • Since the citric acid does both synthesis (anabolic) and breakdown (catabolic) activities, it is called an amphibolic pathway • The citric acid cycle is amphibolic (i.e it is both anabolic and catabolic in its function). • It is said to be an AMPHIBOLIC pathway, because it functions in both degradative or catabolic and biosynthetic or anabolic reactions (amphi = both) A central metabolic pathway or amphibolic pathway is a set of reactions which permit the interconversion of several metabolites, and represents the end of the catabolism and the beginning of anabolism • The KREBS CYCLE or citric acid cycle is a series of reactions that degrades acetyl CoA to yield carbon dioxide, and energy, which is used to produce NADH, H+ and FADH. • The KREBS CYCLE connects the catabolic pathways that begin with the digestion and degradation of foods in stages 1 and 2 with the oxidation of substrates in stage 3 that generates most of the energy for ATP synthesis. • The citric acid cycle is the final common pathway in the oxidation of fuel molecules. In stage 3 of metabolism, citric acid is a final common catabolic intermediate in the form of acetylCoA. • This is why the citric acid cycle is called a central metabolic pathway. Anaplerosis and Cataplerosis Anaplerosis is a series of enzymatic reactions in which metabolic intermediates enter the citric acid cycle from the cytosol. Cataplerosis is the opposite, a process where intermediates leave the citric acid cycle and enter the cytosol.
    [Show full text]
  • Fructose Metabolism from a Functional
    SSE #174 Sports Science Exchange (2017) Vol. 28, No. 174, 1-5 FRUCTOSE METABOLISM FROM A FUNCTIONAL PERSPECTIVE: IMPLICATIONS FOR ATHLETES Luke Tappy, MD | Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Service of Endocrinology, Diabetes and Metabolism | Lausanne University Hospital, and Cardio-metabolic Center, Broye Hospital | Estavayer-le-lac, Switzerland • Fructose was originally a seasonal natural nutrient, mainly consumed in summer and fall in fruits and vegetables. In the industrial era, it became a permanent constituent of our diet, essentially a constituent of added sugars (sucrose, high-fructose corn syrup). • Fructose cannot be directly metabolized by most cells in our body. It has to be processed first in the gut, liver and kidneys, where it is converted into glucose, lactate and fatty acids. • Too much dietary fructose along with excess energy intake and low physical activity can cause hepatic insulin resistance, hypertriglyceridemia and increased hepatic fat content. GAT11LOGO_GSSI_vert_fc_grn • In exercising athletes, net carbohydrate oxidation increases with glucose ingestion in a dose-dependent manner until a plateau is reached at about 1g/min. The addition of fructose to glucose drinks can further increase carbohydrate oxidation. • During exercise, substantial amounts of fructose can be converted into lactate in splanchnic organs if available and released in the systemic circulation to be oxidized in contracting muscles. This “reverse fructose-lactate Cori cycle” provides additional energy substrate to muscle during exercise. • Conversion of fructose into glucose and lactate in splanchnic organs is associated with enhanced splanchnic energy expenditure, while muscle energy efficiency is minimally altered. • During recovery after exercise, glucose and fructose mutually enhance their gut absorption and their storage as glycogen in the liver.
    [Show full text]
  • • Glycolysis • Gluconeogenesis • Glycogen Synthesis
    Carbohydrate Metabolism! Wichit Suthammarak – Department of Biochemistry, Faculty of Medicine Siriraj Hospital – Aug 1st and 4th, 2014! • Glycolysis • Gluconeogenesis • Glycogen synthesis • Glycogenolysis • Pentose phosphate pathway • Metabolism of other hexoses Carbohydrate Digestion! Digestive enzymes! Polysaccharides/complex carbohydrates Salivary glands Amylase Pancreas Oligosaccharides/dextrins Dextrinase Membrane-bound Microvilli Brush border Maltose Sucrose Lactose Maltase Sucrase Lactase ‘Disaccharidase’ 2 glucose 1 glucose 1 glucose 1 fructose 1 galactose Lactose Intolerance! Cause & Pathophysiology! Normal lactose digestion Lactose intolerance Lactose Lactose Lactose Glucose Small Intestine Lactase lactase X Galactose Bacteria 1 glucose Large Fermentation 1 galactose Intestine gases, organic acid, Normal stools osmotically Lactase deficiency! active molecules • Primary lactase deficiency: อาการ! genetic defect, การสราง lactase ลด ลงเมออายมากขน, พบมากทสด! ปวดทอง, ถายเหลว, คลนไสอาเจยนภาย • Secondary lactase deficiency: หลงจากรบประทานอาหารทม lactose acquired/transient เชน small bowel เปนปรมาณมาก เชนนม! injury, gastroenteritis, inflammatory bowel disease! Absorption of Hexoses! Site: duodenum! Intestinal lumen Enterocytes Membrane Transporter! Blood SGLT1: sodium-glucose transporter Na+" Na+" •! Presents at the apical membrane ! of enterocytes! SGLT1 Glucose" Glucose" •! Co-transports Na+ and glucose/! Galactose" Galactose" galactose! GLUT2 Fructose" Fructose" GLUT5 GLUT5 •! Transports fructose from the ! intestinal lumen into enterocytes!
    [Show full text]
  • Regulatory Effects of Cu, Zn, and Ca on Fe Absorption: the Intricate Play Between Nutrient Transporters
    Nutrients 2013, 5, 957-970; doi:10.3390/nu5030957 OPEN ACCESS nutrients ISSN 2072-6643 www.mdpi.com/journal/nutrients Review Regulatory Effects of Cu, Zn, and Ca on Fe Absorption: The Intricate Play between Nutrient Transporters Nathalie Scheers Division of Life Sciences, Food Science, Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden; E-Mail: [email protected]; Tel.: +46-31-772-3821; Fax: +46-31-772-3830 Received: 4 February 2013; in revised form: 8 March 2013 / Accepted: 15 March 2013 / Published: 20 March 2013 Abstract: Iron is an essential nutrient for almost every living organism because it is required in a number of biological processes that serve to maintain life. In humans, recycling of senescent erythrocytes provides most of the daily requirement of iron. In addition, we need to absorb another 1–2 mg Fe from the diet each day to compensate for losses due to epithelial sloughing, perspiration, and bleeding. Iron absorption in the intestine is mainly regulated on the enterocyte level by effectors in the diet and systemic regulators accessing the enterocyte through the basal lamina. Recently, a complex meshwork of interactions between several trace metals and regulatory proteins was revealed. This review focuses on advances in our understanding of Cu, Zn, and Ca in the regulation of iron absorption. Ascorbate as an important player is also considered. Keywords: iron; absorption; Fe; Zn; Cu; Ca; ascorbate 1. Introduction Iron (Fe) is the second most abundant metal on earth and is a necessity for all life. Iron plays the key role in numerous enzymatic reactions due to its ease in shifting between the two common oxidation states, ferrous (Fe2+) and ferric (Fe3+) iron.
    [Show full text]
  • Inhibition of Fructolytic Enzymes in Boar Spermatozoa by (S)-A-Chlorohydrin and L-Chloro-3-Hydroxypropanone
    Aust. J. BioI. Sci., 1986, 39, 395-406 Inhibition of Fructolytic Enzymes in Boar Spermatozoa by (S)-a-Chlorohydrin and l-Chloro-3-hydroxypropanone A. R. Jones, W. A. Bubb, S. R. Murdoch, and D. A. Stevenson Department of Biochemistry, The University of Sydney, New South Wales 2006. Abstract When boar spermatozoa were incubated with the (S)-isomer of the male antifertility agent a-chlorohydrin the activity of glyceraldehyde-3-phosphate dehydrogenase was inhibited. The (R)-isomer had no significant effect on the activity of this enzyme whereas (R,S)-3-chlorolactaldehyde caused an inhibition of its activity and also in that of lactate dehydrogenase. The in vitro production of (S)-3-chlorolactaldehyde, the active metabolite of (S)-a-chlorohydrin, was attempted by incubating boar spermatozoa with l-chloro-3- hydroxypropanone. Preliminary results lead us to propose that this compound is converted into (S)-3- chlorolactaldehyde as well as to another metabolite which is an inhibitor of other enzymes within the fructolytic pathway. Introduction Of the many non-steroidal chemicals which are known to elicit an antifertility response in the male (Jackson 1966), only one compound has most of the attributes of an ideal male contraceptive. This compound, (S)-a-chlorohydrin [(S)-3-chloro­ propan-l,2-diol, I (Fig. 1)], affects the metabolic activity of mature spermatozoa by inhibiting the activity of the glycolytic or fructolytic enzyme glyceraldehyde- 3-phosphate dehydrogenase (Ee 1.2.1.12) thereby causing a decrease in the fructolytic flux. This limits the capability of the spermatozoa to synthesize ATP so that when CHpH I c=o I CH2C1 III Fig.
    [Show full text]
  • Energy Metabolism: Gluconeogenesis and Oxidative Phosphorylation
    International Journal for Innovation Education and Research www.ijier.net Vol:-8 No-09, 2020 Energy metabolism: gluconeogenesis and oxidative phosphorylation Luis Henrique Almeida Castro ([email protected]) PhD in the Health Sciences Graduate Program, Federal University of Grande Dourados Dourados, Mato Grosso do Sul – Brazil. Leandro Rachel Arguello Dom Bosco Catholic University Campo Grande, Mato Grosso do Sul – Brazil. Nelson Thiago Andrade Ferreira Motion Science Graduate Program, Federal University of Mato Grosso do Sul Campo Grande, Mato Grosso do Sul – Brazil. Geanlucas Mendes Monteiro Heath and Development in West Central Region Graduate Program, Federal University of Mato Grosso do Sul Campo Grande, Mato Grosso do Sul – Brazil. Jessica Alves Ribeiro Federal University of Mato Grosso do Sul Campo Grande, Mato Grosso do Sul – Brazil. Juliana Vicente de Souza Motion Science Graduate Program, Federal University of Mato Grosso do Sul Campo Grande, Mato Grosso do Sul – Brazil. Sarita Baltuilhe dos Santos Motion Science Graduate Program, Federal University of Mato Grosso do Sul Campo Grande, Mato Grosso do Sul – Brazil. Fernanda Viana de Carvalho Moreto MSc., Nutrition, Food and Health Graduate Program, Federal University of Grande Dourados Dourados, Mato Grosso do Sul – Brazil. Ygor Thiago Cerqueira de Paula Motion Science Graduate Program, Federal University of Mato Grosso do Sul Campo Grande, Mato Grosso do Sul – Brazil. International Educative Research Foundation and Publisher © 2020 pg. 359 International Journal for Innovation Education and Research ISSN 2411-2933 September 2020 Vanessa de Souza Ferraz Motion Science Graduate Program, Federal University of Mato Grosso do Sul Campo Grande, Mato Grosso do Sul – Brazil. Tayla Borges Lino Motion Science Graduate Program, Federal University of Mato Grosso do Sul Campo Grande, Mato Grosso do Sul – Brazil.
    [Show full text]
  • Fatty Acid Biosynthesis
    BI/CH 422/622 ANABOLISM OUTLINE: Photosynthesis Carbon Assimilation – Calvin Cycle Carbohydrate Biosynthesis in Animals Gluconeogenesis Glycogen Synthesis Pentose-Phosphate Pathway Regulation of Carbohydrate Metabolism Anaplerotic reactions Biosynthesis of Fatty Acids and Lipids Fatty Acids contrasts Diversification of fatty acids location & transport Eicosanoids Synthesis Prostaglandins and Thromboxane acetyl-CoA carboxylase Triacylglycerides fatty acid synthase ACP priming Membrane lipids 4 steps Glycerophospholipids Control of fatty acid metabolism Sphingolipids Isoprene lipids: Cholesterol ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1 ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1. Biosynthesis of fatty acids 2. Regulation of fatty acid degradation and synthesis 3. Assembly of fatty acids into triacylglycerol and phospholipids 4. Metabolism of isoprenes a. Ketone bodies and Isoprene biosynthesis b. Isoprene polymerization i. Cholesterol ii. Steroids & other molecules iii. Regulation iv. Role of cholesterol in human disease ANABOLISM II: Biosynthesis of Fatty Acids & Lipids Lipid Fat Biosynthesis Catabolism Fatty Acid Fatty Acid Degradation Synthesis Ketone body Isoprene Utilization Biosynthesis 2 Catabolism Fatty Acid Biosynthesis Anabolism • Contrast with Sugars – Lipids have have hydro-carbons not carbo-hydrates – more reduced=more energy – Long-term storage vs short-term storage – Lipids are essential for structure in ALL organisms: membrane phospholipids • Catabolism of fatty acids –produces acetyl-CoA –produces reducing
    [Show full text]
  • Beta (Β)-Oxidation of Fatty Acid and Its Associated Disorders
    Vol. 5 (1), pp. 158-172, December, 2018 ©Global Science Research Journals International Journal of Clinical Biochemistry Author(s) retain the copyright of this article. http://www.globalscienceresearchjournals.org/ Review Article Beta (β)-Oxidation of Fatty Acid and its associated Disorders Satyam Prakash Assistant Professor, Dept. of Biochemistry, Janaki Medical College Teaching Hospital, Janakpur, Nepal Mobile: +977-9841603704, E-mail: [email protected] Accepted 18 December, 2018 The lipids of metabolic significance in the mammalian organisms include triacylglycerols, phospholipids and steroids, together with products of their metabolism such as long-chain fatty acids, glycerol and ketone bodies. The fatty acids which are present in the triacylglycerols in the reduced form are the most abundant source of energy and provide energy twice as much as carbohydrates and proteins. Fatty acids represent an important source of energy in periods of catabolic stress related to increased muscular activity, fasting or febrile illness, where as much as 80% of the energy for the heart, skeletal muscles and liver could be derived from them. The prime pathway for the degradation of fatty acids is mitochondrial fatty acid β-oxidation (FAO). The relationship of fat oxidation with the utilization of carbohydrate as a source of energy is complex and depends upon tissue, nutritional state, exercise, development and a variety of other influences such as infection and other pathological states. Inherited defects for most of the FAO enzymes have been identified and characterized in early infancy as acute life-threatening episodes of hypoketotic, hypoglycemic coma induced by fasting or febrile illness. Therefore, this review briefly highlights mitochondrial β-oxidation of fatty acids and associated disorders with clinical manifestations.
    [Show full text]
  • Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive And
    nutrients Article Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases Jana Ruiz Herrero 1,* , Elvira Cañedo Villarroya 2 , Luis González Gutiérrez-Solana 3,4 , Beatriz García Alcolea 2, Begoña Gómez Fernández 2, Laura Andrea Puerta Macfarland 2 and Consuelo Pedrón-Giner 2 1 Department of Pediatric Gastroenterology, Pediatric Service, San Rafael Hospital, 28016 Madrid, Spain 2 Department of Gastroenterology and Nutrition, University Children’s Hospital Niño Jesús, 28009 Madrid, Spain; [email protected] (E.C.V.); [email protected] (B.G.A.); [email protected] (B.G.F.); [email protected] (L.A.P.M.); [email protected] (C.P.-G.) 3 Department of Neurology, University Children’s Hospital Niño Jesús, 28009 Madrid, Spain; [email protected] 4 Center for Biomedical Network Research on Rare Diseases (CIBERER), Health Institute Carlos III, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-915-035-933 Citation: Ruiz Herrero, J.; Cañedo Villarroya, E.; González Abstract: Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused Gutiérrez-Solana, L.; García Alcolea, by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and B.; Gómez Fernández, B.; Puerta Macfarland, L.A.; Pedrón-Giner, C. movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar Classic Ketogenic Diet and Modified symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness Atkins Diet in SLC2A1 Positive and of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact Negative Patients with Suspected on patients nutritional status.
    [Show full text]
  • A Short Review of Iron Metabolism and Pathophysiology of Iron Disorders
    medicines Review A Short Review of Iron Metabolism and Pathophysiology of Iron Disorders Andronicos Yiannikourides 1 and Gladys O. Latunde-Dada 2,* 1 Faculty of Life Sciences and Medicine, Henriette Raphael House Guy’s Campus King’s College London, London SE1 1UL, UK 2 Department of Nutritional Sciences, School of Life Course Sciences, King’s College London, Franklin-Wilkins-Building, 150 Stamford Street, London SE1 9NH, UK * Correspondence: [email protected] Received: 30 June 2019; Accepted: 2 August 2019; Published: 5 August 2019 Abstract: Iron is a vital trace element for humans, as it plays a crucial role in oxygen transport, oxidative metabolism, cellular proliferation, and many catalytic reactions. To be beneficial, the amount of iron in the human body needs to be maintained within the ideal range. Iron metabolism is one of the most complex processes involving many organs and tissues, the interaction of which is critical for iron homeostasis. No active mechanism for iron excretion exists. Therefore, the amount of iron absorbed by the intestine is tightly controlled to balance the daily losses. The bone marrow is the prime iron consumer in the body, being the site for erythropoiesis, while the reticuloendothelial system is responsible for iron recycling through erythrocyte phagocytosis. The liver has important synthetic, storing, and regulatory functions in iron homeostasis. Among the numerous proteins involved in iron metabolism, hepcidin is a liver-derived peptide hormone, which is the master regulator of iron metabolism. This hormone acts in many target tissues and regulates systemic iron levels through a negative feedback mechanism. Hepcidin synthesis is controlled by several factors such as iron levels, anaemia, infection, inflammation, and erythropoietic activity.
    [Show full text]
  • Regulation of Ketone Body and Coenzyme a Metabolism in Liver
    REGULATION OF KETONE BODY AND COENZYME A METABOLISM IN LIVER by SHUANG DENG Submitted in partial fulfillment of the requirements For the Degree of Doctor of Philosophy Dissertation Adviser: Henri Brunengraber, M.D., Ph.D. Department of Nutrition CASE WESTERN RESERVE UNIVERSITY August, 2011 SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of __________________ Shuang Deng ____________ _ _ candidate for the ________________________________degree Doctor of Philosophy *. (signed) ________________________________________________ Edith Lerner, PhD (chair of the committee) ________________________________________________ Henri Brunengraber, MD, PhD ________________________________________________ Colleen Croniger, PhD ________________________________________________ Paul Ernsberger, PhD ________________________________________________ Janos Kerner, PhD ________________________________________________ Michelle Puchowicz, PhD (date) _______________________June 23, 2011 *We also certify that written approval has been obtained for any proprietary material contained therein. I dedicate this work to my parents, my son and my husband TABLE OF CONTENTS Table of Contents…………………………………………………………………. iv List of Tables………………………………………………………………………. viii List of Figures……………………………………………………………………… ix Acknowledgements………………………………………………………………. xii List of Abbreviations………………………………………………………………. xiv Abstract…………………………………………………………………………….. xvii CHAPTER 1: KETONE BODY METABOLISM 1.1 Overview……………………………………………………………………….. 1 1.1.1 General introduction
    [Show full text]
  • Bacterial Protein Systems at the Membrane Interface Structural and Biophysical Studies of the E
    Bacterial protein systems at the membrane interface Structural and biophysical studies of the E. coli adhesion receptor intimin and the magnesium transporter MgtA Dissertation for the degree of Ph.D. by Julia Anna Weikum Centre for Molecular Medicine Norway Nordic EMBL Partnership for Molecular Medicine University of Oslo July 2020 © Julia Anna Weikum, 2020 Series of dissertations submitted to the Faculty of Mathematics and Natural Sciences, University of Oslo No. 2316 ISSN 1501-7710 All rights reserved. No part of this publication may be reproduced or transmitted, in any form or by any means, without permission. Cover: Hanne Baadsgaard Utigard. Print production: Reprosentralen, University of Oslo. Table of contents Acknowledgments ...................................................................................................................III List of publications ................................................................................................................. IV Abbreviations ........................................................................................................................... V 1. Introduction .......................................................................................................................... 1 1.1 Pathogenic Escherichia coli .............................................................................................. 2 1.1.1 Enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) .................. 2 1.2 Adhesion .........................................................................................................................
    [Show full text]