DOCSLIB.ORG

De Novo Lipogenesis in the Liver in Health and Disease: More Than Just a Shunting Yard for Glucose

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
De Novo Lipogenesis in the Liver in Health and Disease: More Than Just a Shunting Yard for Glucose Biol. Rev. (2016), 91, pp. 452–468. 452 doi: 10.1111/brv.12178 De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose Francis W. B. Sanders1,2 and Julian L. Griffin1,2,∗ 1MRC Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, U.K. 2The Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K. ABSTRACT Hepatic de novo lipogenesis (DNL) is the biochemical process of synthesising fatty acids from acetyl-CoA subunits that are produced from a number of different pathways within the cell, most commonly carbohydrate catabolism. In addition to glucose which most commonly supplies carbon units for DNL, fructose is also a profoundly lipogenic substrate that can drive DNL, important when considering the increasing use of fructose in corn syrup as a sweetener. In the context of disease, DNL is thought to contribute to the pathogenesis of non-alcoholic fatty liver disease, a common condition often associated with the metabolic syndrome and consequent insulin resistance. Whether DNL plays a significant role in the pathogenesis of insulin resistance is yet to be fully elucidated, but it may be that the prevalent products of this synthetic process induce some aspect of hepatic insulin resistance. Key words: de novo lipogenesis (DNL), non-alcoholic fatty liver disease (NAFLD), fructose, liver, selective insulin resistance. CONTENTS I. Introduction .............................................................................................. 453 II. The biochemical process of DNL ........................................................................ 453 III. VLDL production and assembly ......................................................................... 455 IV. The regulation of hepatic DNL .......................................................................... 455 (1) SREBP1c ............................................................................................. 455 (2) ChREBP ............................................................................................. 457 (3) ACC .................................................................................................. 458 V. DNL: A Contributor to NAFLD ......................................................................... 460 VI. NAFLD as a component of metabolic syndrome and type 2 diabetes mellitus ........................... 460 VII. Selective insulin resistance promotes hepatic DNL ....................................................... 461 VIII. Anatomical zonation of the metabolic processes in the liver may underlie ‘selective’ insulin resistance ... 462 IX. Fructose, DNL and hepatic steatosis ..................................................................... 463 X. Fructose and the gut microbiome ........................................................................ 463 XI. Conclusions .............................................................................................. 464 XII. Acknowledgements ....................................................................................... 464 XIII. References ................................................................................................ 464 * Address for correspondence (Tel: 01223 437503; E-mail: Jules.griffi[email protected]). Biological Reviews 91 (2016) 452–468 © 2015 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Hepatic de novo lipogenesis and metabolic disease 453 I. INTRODUCTION Initially this is an acetyl unit bound to the thiol group of cysteine (Cys161)attheβ-ketoacyl synthase (KS) active Hepatic de novo lipogenesis (DNL) is a fundamental site (Witkowski, Joshi & Smith, 1997). The malonyl moiety biosynthetic pathway within the liver, contributing to undergoes decarboxylative condensation with an acetyl the lipids that are stored and secreted by hepatocytes moiety, as elucidated in Fig. 1 (von Wettstein-Knowles et al., (Jensen-Urstad & Semenkovich, 2012). This process is an 2006). ACP is then bound to a β-ketoacyl intermediate. extension of the complex metabolic networks at play within ACP shuttles the β-ketoacyl intermediate to the the liver, and is provided with substrate primarily through NADPH-dependent β-ketoreductase (KR) active site glycolysis and the metabolism of carbohydrates. Therefore, a (Chang & Hammes, 1990). The ketone of the β-carbon high-carbohydrate diet can prime the DNL pathway with a is reduced, generating a hydroxyl group. This is followed large substrate load and increase rates of DNL (Schwarz et al., by sequential dehydration, by the dehydratase (DH) 2003). Importantly this leads to an accumulation of DNL active site, and further reduction by NADPH-dependent products, fatty acyl chains linked to coenzyme A, which can enoyl-reductase (EnR) (Wakil, 1989; Chang & Hammes, be incorporated into a plethora of lipid species. These lipids 1990; Smith & Tsai, 2007). This generates a saturated acyl may then have further metabolic functions, which in turn chain elongated by two carbon groups, which can act as may be deleterious in cases of elevated DNL. the substrate for the next round of elongation as it binds the DNL has been suggested to be abnormally increased in thiol-group of the cysteine at the catalytic site of KS. and contribute to the pathogenesis of non-alcoholic fatty liver The elongation ceases at the 16- or 18-carbon stage disease (NAFLD) (Donnelly et al., 2005), a highly prevalent (Foster & Bloom, 1963; Carey, Dils & Hansen, 1970) with metabolic disease that is linked to the development of type release of palmitic acid or stearic acid from ACP via activity 2 diabetes mellitus (T2DM). DNL is also increased under of the thioesterase (TE) domain of FAS (Chakravarty et al., conditions of insulin resistance (Ameer et al., 2014), and thus 2004; Smith & Tsai, 2007). The specificity of FAS TE for knowing the rate of DNL in an individual may benefit the 16-carbon acyl dictates the length of the FAs released in vitro clinician as it would provide early warning of the possible as there is a rapid decline of TE activity for chain lengths development of T2DM. This is especially important as recent less than 14-carbons (Lin & Smith, 1978; Chakravarty et al., evidence suggests that ‘prediabetes’, a state of mildly elevated 2004), as it will not access the catalytic core of the domain, blood glucose, has increased significantly from 11.6% in 2003 and greater than 18-carbons as it may not be accommodated to 35.3% in 2011 amongst adults in England (Mainous et al., by the binding groove of TE (Chakravarty et al., 2004). The 2014). Therefore it may be crucial to understand and map termination of chain elongation at this 16- carbon stage is the full spectrum of metabolic disturbances associated with further promoted due to acyl chains of this length or longer insulin resistance, including rates of DNL. not readily transferring to the thiol-group of the active-site cysteine of KS (Witkowski et al., 1997). The incorporation of stable-isotope-labelled precursors into palmitate in humans, 3 and tritium from H2O in rat liver also supports palmitate II. THE BIOCHEMICAL PROCESS OF DNL as the major product of DNL (Foster & Bloom, 1963; Hellerstein et al., 1991; Murphy, 2006). DNL is the synthesis of fatty acid (FA) chains from acetyl-CoA While glucose is the main substrate for DNL, fructose subunits produced during glycolysis (Smith & Tsai, 2007) and is a highly lipogenic substrate (Dekker et al., 2010) these can undergo subsequent condensation with a glycerol and this is thought to arise from it bypassing the backbone (Coleman & Lee, 2004) (Fig. 1). critical regulatory step catalysed by phosphofructokinase-1 The reaction mechanism commences with the production (PFK-1) in glycolysis (Basaranoglu, 2013). Fructose is of malonyl-CoA from an acetyl-CoA precursor, under the phosphorylated by fructokinase in the liver to fructose regulated catalytic activity of acetyl-CoA carboxylase (ACC) 1-phosphate (F1P) (Hers, 1952). F1P is then the (Bianchi et al., 1990). The malonyl-CoA is transferred to substrate for catalytic cleavage by aldolase, generating the prosthetic phosphopantetheine group of acyl carrier dihydroxy-acetone-phosphate (DHAP) and glyceraldehyde. protein (ACP) (Majerus, Alberts & Vagelos, 1964), a Glyceraldehyde is subsequently phosphorylated by triokinase domain of the type I fatty acid synthase complex (FAS) to produce glyceraldehyde 3-phosphate (G3P) (Mayes, 1993). (Brindley, Matsumura & Bloch, 1969; Smith, 1994), with Thus G3P and DHAP can enter glycolysis (Fig. 2). This subsequent release of the coenzyme A carrier, catalysed by has implications that mean fructose may reinforce some of the activity of the malonyl/acetyl transferase (MAT) site the pathogenic mechanisms leading to NAFLD (Laville & of mammalian FAS (Mikkelsen et al., 1985). The prosthetic Nazare, 2009; Basaranoglu, 2013), as discussed in Sections phosphopantetheine arm of ACP thus shuttles the elongating IX and X. FA chain to the various catalytic centres in the active site cleft During de novo triacylglycerol (TG) synthesis FAs are of FAS, aided by the rotation of FAS (Wakil, 1989; Smith & incorporated through the initial acylation, by acyl-CoA, Tsai, 2007; Maier, Leibundgut & Ban, 2008). of glycerol-3-phosphate,
Load more

Recommended publications
  • • 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]
  • The Metabolism of Subcutaneous Adipose Tissue in the Immediate Postnatal Period of Human Newborns
    Pediat. Res. 6: 211-218 (1972) Adipose tissue glucose metabolism /3-hydroxyacyl-CoA dehydrogenase neonates fatty acid catabolism phosphofructokinase The Metabolism of Subcutaneous Adipose Tissue in the Immediate Postnatal Period of Human Newborns. 2. Developmental Changes in the Metabolism of 14C-(U)-D-Glucose and in Enzyme Activities of Phosphofructo- kinase (PFK; EC. 2.7.1.11) and /3-Hydroxyacyl-CoA Dehydro- genase (HAD; EC. 1.1.1.35) M. NOVAK1351, E. MONKUS, H. WOLF, AND U. STAVE Department of Pediatrics, University of Miami School of Medicine, Miami, Florida, USA, Staedtische Kinderklinik, Kassel, West Germany, and Fels Research Institute, Yellow Springs, Ohio, USA Extract Changes in the in vitro metabolism of subcutaneous adipose tissue have been compared in normal human newborns from 2 hr to 2 weeks of age. A group of healthy adult volunteers was also included. Samples were obtained by using a needle biopsy tech- nique. More of the isotope from uC-(U)-D-glucose was incorporated into triglyc- erides (P < 0.05) and also oxidized by suspensions of adipose cells from infants 2-3 hr of age than in older infants (P < 0.01). The ratio of radioactivity in carbon dioxide to radioactivity in triglyceride was also significantly greater in 2- to 3-hr-old infants than in older neonates (P < 0.05). Thin layer chromatography of the total lipid ex- tract showed the greatest amount of radioactivity in the triglycerides, a small amount in 1,3-digiycerides and 1,2-diglycerides, and a trace in fatty acids and monogiyc- erides. These findings were compared with the developmental changes in two key enzymes: phosphofructokinase (PFK), which represents the glycolytic pathway, and (3-hydroxyacyl-coenzyme A (GoA) dehydrogenase (HAD), which is involved in the P oxidation of fatty acids.
    [Show full text]
  • Chapter 12 Slides
    11/15/17 CHAPTER 12: Carbohydrates: Structure and Function OUTLINE • 12.1 Role of Carbohydrates • 12.2 Monosaccharides • 12.3 Complex Carbohydrates • 12.4 Carbohydrate Catabolism • 12.5 Oligosaccharides as Cell Markers CHAPTER 12: Carbohydrates: Structure and Function WHAT ARE CARBOHYDRATES? • Glucose and its derivatives are carbohydrates: Ø Carbohydrates are simple organic molecules that have a shared basic chemical Formula: Cn(H2O)n Ø The name “carbo + hydrate” represents that Fact that they are made from CO2 and H2O by photosynthesis • About halF oF all earth’s solid carbon is Found in two polymers of glucose found in plants: Ø Starch = major energy storage molecule Ø Cellulose = major structural component oF the plant cell wall (aka. “fiber”) CHAPTER 12: Carbohydrates: Structure and Function THE SIMPLEST CARBOHYDRATES • Monosaccharides are carbohydrates that cannot be hydrolyZed into simpler carbohydrates: Ø These are the Fundamental building blocks For all other carbohydrates (oFten called “simple sugars”) Ø All have Formulas of based on the basic pattern: Cn(H2O)n • Monosaccharides have speciFic Functional groups: 1. An aldehyde OR a ketone (not both!) 2. Several (two or more) alcohol (-OH) groups 1 11/15/17 CHAPTER 12: Carbohydrates: Structure and Function STRUCTURE & NOMENCLATURE OF MONOSACCHARIDES • Monosaccharides are classiFied by two features: 1. Length of their main carbon chain (utilize standard IUPAC naming For # oF carbons) 2. Whether they contain an aldehyde or ketone group • Names always end with –ose • Two common hexoses:
    [Show full text]
  • Structures, Functions, and Mechanisms of Filament Forming Enzymes: a Renaissance of Enzyme Filamentation
    Structures, Functions, and Mechanisms of Filament Forming Enzymes: A Renaissance of Enzyme Filamentation A Review By Chad K. Park & Nancy C. Horton Department of Molecular and Cellular Biology University of Arizona Tucson, AZ 85721 N. C. Horton ([email protected], ORCID: 0000-0003-2710-8284) C. K. Park ([email protected], ORCID: 0000-0003-1089-9091) Keywords: Enzyme, Regulation, DNA binding, Nuclease, Run-On Oligomerization, self-association 1 Abstract Filament formation by non-cytoskeletal enzymes has been known for decades, yet only relatively recently has its wide-spread role in enzyme regulation and biology come to be appreciated. This comprehensive review summarizes what is known for each enzyme confirmed to form filamentous structures in vitro, and for the many that are known only to form large self-assemblies within cells. For some enzymes, studies describing both the in vitro filamentous structures and cellular self-assembly formation are also known and described. Special attention is paid to the detailed structures of each type of enzyme filament, as well as the roles the structures play in enzyme regulation and in biology. Where it is known or hypothesized, the advantages conferred by enzyme filamentation are reviewed. Finally, the similarities, differences, and comparison to the SgrAI system are also highlighted. 2 Contents INTRODUCTION…………………………………………………………..4 STRUCTURALLY CHARACTERIZED ENZYME FILAMENTS…….5 Acetyl CoA Carboxylase (ACC)……………………………………………………………………5 Phosphofructokinase (PFK)……………………………………………………………………….6
    [Show full text]
  • The Microbiota-Produced N-Formyl Peptide Fmlf Promotes Obesity-Induced Glucose
    Page 1 of 230 Diabetes Title: The microbiota-produced N-formyl peptide fMLF promotes obesity-induced glucose intolerance Joshua Wollam1, Matthew Riopel1, Yong-Jiang Xu1,2, Andrew M. F. Johnson1, Jachelle M. Ofrecio1, Wei Ying1, Dalila El Ouarrat1, Luisa S. Chan3, Andrew W. Han3, Nadir A. Mahmood3, Caitlin N. Ryan3, Yun Sok Lee1, Jeramie D. Watrous1,2, Mahendra D. Chordia4, Dongfeng Pan4, Mohit Jain1,2, Jerrold M. Olefsky1 * Affiliations: 1 Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA. 2 Department of Pharmacology, University of California, San Diego, La Jolla, California, USA. 3 Second Genome, Inc., South San Francisco, California, USA. 4 Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA. * Correspondence to: 858-534-2230, [email protected] Word Count: 4749 Figures: 6 Supplemental Figures: 11 Supplemental Tables: 5 1 Diabetes Publish Ahead of Print, published online April 22, 2019 Diabetes Page 2 of 230 ABSTRACT The composition of the gastrointestinal (GI) microbiota and associated metabolites changes dramatically with diet and the development of obesity. Although many correlations have been described, specific mechanistic links between these changes and glucose homeostasis remain to be defined. Here we show that blood and intestinal levels of the microbiota-produced N-formyl peptide, formyl-methionyl-leucyl-phenylalanine (fMLF), are elevated in high fat diet (HFD)- induced obese mice. Genetic or pharmacological inhibition of the N-formyl peptide receptor Fpr1 leads to increased insulin levels and improved glucose tolerance, dependent upon glucagon- like peptide-1 (GLP-1). Obese Fpr1-knockout (Fpr1-KO) mice also display an altered microbiome, exemplifying the dynamic relationship between host metabolism and microbiota.
    [Show full text]
  • Aerobic and Nitrate Respiration Routes of Carbohydrate Catabolism in Pseudomonas S Tut Zeri
    AN ABSTRACT OF THE THESIS OF WILLIAM JAN SPANGLER for the Ph. D. in MICROBIOLOGY (Name) (Degree) (Major) thesis is presented Date 7 / `> /q6! Title AEROBIC AND NITRATE RESPIRATION ROUTES OF CAR- BOHYDRATE CATABOLISM IN PSEUDOMONAS STUTZERI Abstract approved ( Major professor) Pseudomonas stutzeri and other denitrifying bacteria are able to grow under anaerobic conditions, using nitrate -oxygen as the terminal hydrogen acceptor, in a manner analagous to classical aerobic respiration with free -molecular oxygen. This rather unique phenomenon is known as nitrate respiration. Nitrate respiration has been studied with respect to the nitrate reducing enzymes and carrier systems involved in the reduction sequence, but very little emphasis has been placed on the metabolic pathways which are associated with nitrate respiration. This study was carried out in an attempt to establish the metabolic pathways operative, both under aerobic con- ditions and during nitrate respiration, in order to determine whether there was any shift of pathways under conditions of nitrate respira- tion. Primary pathways were determined by the radiorespirometric method using specifically labelled glucose and gluconate. The results, based primarily on the rate of decarboxylation of the C -1 and C -4 positions of glucose, indicated the operation of the Entner- Doudoroff and pentose phosphate pathways under both aerobic condi- tions and conditions of nitrate respiration. Evolution of 14CO2 from the other labels of glucose, as well as incorporation of these labels into the cell, indicated that terminal pathways such as the tricar- boxylic acid cycle or glyoxalate cycle might also be operative under both conditions of oxygen relationship. The secondary pathways were studied using specifically labelled acetate.
    [Show full text]
  • Specific Catabolic Pathways
    Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 1 Chemistry 1506: Allied Health Chemistry 2 Section 12: Specific Catabolic Pathways Molecular Destruction Outline SECTION 12.1 GENERAL FLOW OF CATABOLIC PATHWAYS..............................................................2 SECTION 12.2 GLYCOLYSIS ............................................................................................................................6 SECTION 12.3 TRIGLYCERIDE METABOLISM ..........................................................................................7 2000-2002, Dr. Allen D. Hunter, Department of Chemistry, Youngstown State University Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 2 Section 12.1 General Flow of Catabolic Pathways Overall Process Start with complex mixtures of food molecules Used to generate energy (as “fuel” molecules) ATP NADH and FADH2 Acetyl CoA Ultimate products are CO2, H2O, Urea (C(O)(NH2)2), etc. Intermediate Breakdown products may be used in Anabolic pathways 2000-2002, Dr. Allen D. Hunter, Department of Chemistry, Youngstown State University Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 3 Carbohydrate Catabolism 1st stages can start in the digestive tract Final stage is called glycolysis and finishes within the mitochondrion Polysaccharides ⇓ Oligosaccharides ⇓ Disaccharides ⇓ Monosaccharides ⇓ CO2 + “fuel” molecules 2000-2002, Dr. Allen D. Hunter, Department of Chemistry, Youngstown State University Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 4 Lipid Catabolism Starts in digestive system and ends inside mitochondria Lipases break the ester linkages in the triglycerides Triglycerides ⇓ Glycerol + Fatty Acids ⇓ ⇓ CO2 + “fuel” molecules 2000-2002, Dr. Allen D. Hunter, Department of Chemistry, Youngstown State University Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 5 Protein Catabolism Starts in digestive system and ends inside mitochondria Proteins ⇓ Peptides ⇓ Amino Acids ⇓ CO2 + “fuel” molecules + Urea 2000-2002, Dr.
    [Show full text]
  • Nutritional Determinants of Metabolic Diseases in Humans
    Unicentre CH-1015 Lausanne http://serval.unil.ch Year : 2019 NUTRITIONAL DETERMINANTS OF METABOLIC DISEASES IN HUMANS Surowska Anna Surowska Anna, 2019, NUTRITIONAL DETERMINANTS OF METABOLIC DISEASES IN HUMANS Originally published at : Thesis, University of Lausanne Posted at the University of Lausanne Open Archive http://serval.unil.ch Document URN : urn:nbn:ch:serval-BIB_635D730749F67 Droits d’auteur L'Université de Lausanne attire expressément l'attention des utilisateurs sur le fait que tous les documents publiés dans l'Archive SERVAL sont protégés par le droit d'auteur, conformément à la loi fédérale sur le droit d'auteur et les droits voisins (LDA). A ce titre, il est indispensable d'obtenir le consentement préalable de l'auteur et/ou de l’éditeur avant toute utilisation d'une oeuvre ou d'une partie d'une oeuvre ne relevant pas d'une utilisation à des fins personnelles au sens de la LDA (art. 19, al. 1 lettre a). A défaut, tout contrevenant s'expose aux sanctions prévues par cette loi. Nous déclinons toute responsabilité en la matière. Copyright The University of Lausanne expressly draws the attention of users to the fact that all documents published in the SERVAL Archive are protected by copyright in accordance with federal law on copyright and similar rights (LDA). Accordingly it is indispensable to obtain prior consent from the author and/or publisher before any use of a work or part of a work for purposes other than personal use within the meaning of LDA (art. 19, para. 1 letter a). Failure to do so will expose offenders to the sanctions laid down by this law.
    [Show full text]
  • Overexpression of a Biotic Stress-Inducible Pvgstu Gene Activates Early Protective Responses in Tobacco Under Combined Heat and Drought
    International Journal of Molecular Sciences Article Overexpression of A Biotic Stress-Inducible Pvgstu Gene Activates Early Protective Responses in Tobacco under Combined Heat and Drought Evangelia Stavridou 1,2 , Georgia Voulgari 1, Michail Michailidis 3 , Stefanos Kostas 4 , Evangelia G. Chronopoulou 5, Nikolaos E. Labrou 5 , Panagiotis Madesis 2,6 and Irini Nianiou-Obeidat 1,* 1 Laboratory of Genetics and Plant Breeding, School of Agriculture, Forestry and Natural Environment, Aristotle University of Thessaloniki, P.O. Box 261, GR-54124 Thessaloniki, Greece; [email protected] (E.S.); [email protected] (G.V.) 2 Institute of Applied Biosciences, CERTH, 6th km Charilaou-Thermis Road, Thermi, P.O. Box 361, GR-57001 Thessaloniki, Greece; [email protected] 3 Laboratory of Pomology, Department of Horticulture, School of Agriculture, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; [email protected] 4 Laboratory of Floriculture, School of Agriculture, Forestry and Natural Environment, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; [email protected] 5 Laboratory of Enzyme Technology, Department of Biotechnology, School of Food, Biotechnology and Development, Agricultural University of Athens, 75 Iera Odos Street, 11855 Athens, Greece; [email protected] (E.G.C.); [email protected] (N.E.L.) 6 Laboratory of Molecular Biology of Plants, School of Agricultural Sciences, University of Thessaly, Citation: Stavridou, E.; Voulgari, G.; 38446 Thessaly, Greece Michailidis, M.; Kostas, S.; * Correspondence: [email protected]; Tel.: +30-2310-998-617 Chronopoulou, E.G.; Labrou, N.E.; Madesis, P.; Nianiou-Obeidat, I. Abstract: Drought and heat stresses are major factors limiting crop growth and productivity, and Overexpression of A Biotic their effect is more devastating when occurring concurrently.
    [Show full text]
  • Energy Production in a Cell (Chapter 25 Metabolism)
    Energy Production In A Cell (Chapter 25 Metabolism) Large food molecules contain a lot of potential energy in the form of chemical bonds but it requires a lot of work to liberate the energy. Cells need a quick easy way to get energy for anabolism: this is done with ATP. ATP is an unstable molecule, the bonds of which are easy to break making it a useful source of energy for cells. ATP → ADP + P + free energy from food Food energy + ADP + P → ATP Catabolic reactions generate energy to make ATP, and the ATP energy is used to drive anabolic reactions, such as metabolic turnover (replacement of cell parts), growth and cell division, and special functions (such as secretion, absorption, contraction, or signaling). Metabolism = the sum of all chemical reactions in the body; catabolism + anabolism All energy production begins in the cytosol of the cell. Large molecules are catabolized into smaller molecules, but very little energy is produced: Proteins → amino acids Triglycerides → fatty acids and glycerol Carbohydrates → short carbon chains These smaller molecules are then absorbed and processed in reactions inside the mitochondria. 40% of the energy is captured to produce ATP from ADP and the remaining 60% escapes as heat (used to maintain body temperature). Oxidation-Reduction Reactions (Redox Rxns) Oxidation = the removal of electrons (or addition of oxygen) Reduction = the addition of electrons These reactions are always coupled: one molecule must be oxidized while another is reduced. A-e’ + B → A + B-e’ (A is oxidized while B is reduced) The reduced molecule gains energy while the oxidized molecule loses energy.
    [Show full text]
  • 2 Points Chem 465 Biochemistry II Test 1 Spring 2017 Multiple Choice
    Name: 2 points Chem 465 Biochemistry II Test 1 Spring 2017 Multiple choice (4 points apiece): 1. Which of the following statements about the oxidative decarboxylation of pyruvate in aerobic conditions in animal cells is correct? A) One of the products of the reactions of the pyruvate dehydrogenase complex is a thioester of acetate. B) The methyl (-CH3) group is eliminated as CO2. C) The process occurs in the cytosolic compartment of the cell. D) The pyruvate dehydrogenase complex uses all of the following as cofactors: NAD+, lipoic acid, pyridoxal phosphate (PLP), and FAD. E) The reaction is so important to energy production that pyruvate dehydrogenase operates at full speed under all conditions. 2. In comparison with the resting state, actively contracting human muscle tissue has a: A) higher concentration of ATP. B) higher rate of lactate formation. C) lower consumption of glucose. D) lower rate of consumption of oxygen E) lower ratio of NADH to NAD+. 3.The metabolic function of the pentose phosphate pathway is: A) act as a source of ADP biosynthesis. B) generate NADPH and pentoses for the biosynthesis of fatty acids and nucleic acids. C) participate in oxidation-reduction reactions during the formation of H2O. D) provide intermediates for the citric acid cycle. E) synthesize phosphorus pentoxide. 4. Gluconeogenesis must use "bypass reactions" to circumvent three reactions in the glycolytic pathway that are highly exergonic and essentially irreversible. Reactions carried out by which three of the enzymes listed must be bypassed in the gluconeogenic pathway? 1) Hexokinase 2) Phosphoglycerate kinase 3) Phosphofructokinase-1 4) Pyruvate kinase 5) Triosephosphate isomerase A) 1, 2, 3 B) 1, 2, 4 C) 1, 4, 5 D) 1, 3, 4 E) 2, 3, 4 5.
    [Show full text]
  • Insights Into the Hexose Liver Metabolism—Glucose Versus Fructose
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2017 Insights into the Hexose Liver Metabolism-Glucose versus Fructose Geidl-Flueck, Bettina ; Gerber, Philipp A Abstract: High-fructose intake in healthy men is associated with characteristics of metabolic syndrome. Extensive knowledge exists about the differences between hepatic fructose and glucose metabolism and fructose-specific mechanisms favoring the development of metabolic disturbances. Nevertheless, the causal relationship between fructose consumption and metabolic alterations is still debated. Multiple effects of fructose on hepatic metabolism are attributed to the fact that the liver represents the major sink of fructose. Fructose, as a lipogenic substrate and potent inducer of lipogenic enzyme expression, enhances fatty acid synthesis. Consequently, increased hepatic diacylglycerols (DAG) are thought to directly interfere with insulin signaling. However, independently of this effect, fructose may also counteract insulin-mediated effects on liver metabolism by a range of mechanisms. It may drive gluconeogenesis not only as a gluconeogenic substrate, but also as a potent inducer of carbohydrate responsive element binding protein (ChREBP), which induces the expression of lipogenic enzymes as well as gluconeogenic enzymes. It remains a challenge to determine the relative contributions of the impact of fructose on hepatic transcriptome, proteome and allosterome changes and consequently on the regulation of plasma glucose metabolism/homeostasis. Mathematical models exist modeling hepatic glucose metabolism. Fu- ture models should not only consider the hepatic adjustments of enzyme abundances and activities in response to changing plasma glucose and insulin/glucagon concentrations, but also to varying fructose concentrations for defining the role of fructose in the hepatic control of plasma glucose homeostasis.
    [Show full text]