DOCSLIB.ORG

Increased Protein-Energy Intake Promotes Anabolism in Critically Ill

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Increased Protein-Energy Intake Promotes Anabolism in Critically Ill ADC Online First, published on June 14, 2011 as 10.1136/adc.2010.185637 Original article Arch Dis Child: first published as 10.1136/adc.2010.185637 on 14 June 2011. Downloaded from I n c r e a s e d p r o t e i n - e n e r g y i n t a k e p r o m o t e s a n a b o l i s m in critically ill infants with viral bronchiolitis: a double-blind randomised controlled trial C a r l i j n T d e B e t u e , 1,3 D i c k A v a n W a a r d e n b u r g ,1,2 N i c o l a a s E D e u t z , 4,5 Hans M van Eijk, 4 Johannes B van Goudoever,6,7,8 Y v e t t e C L u i k i n g ,3,4 L u c J Z i m m e r m a n n , 2 K o e n F J o o s t e n 8 ▶ Appendices 1–4 are available A B S T R A C T online only. To view these fi les O b j e c t i v e The preservation of nutritional status and What is already known on this topic please visit the journal online (http://adc.bmjgroup.com) growth is an important aim in critically ill infants, but diffi cult to achieve due to the metabolic stress response ▶ 1 Critical illness in children is associated with Department of Paediatrics, and inadequate nutritional intake, leading to negative Maastricht University increased protein breakdown, negative protein Medical Center, Maastricht, protein balance. This study investigated whether balance and adverse clinical outcome. The Netherlands increasing protein and energy intakes can promote ▶ Inadequate nutritional support further leads to 2 Department of Paediatric anabolism. The primary outcome was whole body protein-energy malnutrition during admission Surgery, Erasmus MC– Sophia protein balance, and the secondary outcome was fi rst to the paediatric intensive care unit. Children’s Hospital, Rotterdam, The Netherlands pass splanchnic phenylalanine extraction (SPE Phe ). 3 Currently working: D e s i g n This was a double-blind randomised controlled Department of Paediatric trial. Infants (n=18) admitted to the paediatric What t his study adds Surgery, ErasmusMC-Sophia intensive care unit with respiratory failure due to Children’s Hospital, Rotterdam, viral bronchiolitis were randomised to continuous The Netherlands ▶ Protein anabolism in critically ill infants can be 4 enteral feeding with protein and energy enriched Department of Surgery, achieved in the fi rst days after admission by Maastricht University Medical formula (PE-formula) (n=8; 3.1±0.3 g protein/kg/24 h, Center, Maastricht, the 119±25 kcal/kg/24 h) or standard formula (S-formula) increasing protein and energy intakes above Netherlands reference levels. 5 (n=10; 1.7±0.2 g protein/kg/24 h, 84±15 kcal/ Currently working: Center kg/24 h; equivalent to recommended intakes for healthy ▶ The higher protein balance resulted from for Translational Research in stimulated protein synthesis exceeding the rate Aging and Longevity, Donald infants <6 months). A combined intravenous-enteral W Reynolds Insitute on Aging, phenylalanine stable isotope protocol was used on day of concomitant stimulated protein breakdown. University of Arkansas for 5 after admission to determine whole body protein ▶ Increased protein and energy intakes are Medical Sciences, Little Rock, metabolism and SPE . recommended in critically ill infants with viral AR, USA Phe bronchiolitis. http://adc.bmj.com/ 6Department of Paedatrics, R e s u l t s Protein balance was signifi cantly higher with VU University Medical Center, PE-formula than with S-formula (PE-formula: 0.73±0.5 Amsterdam, the Netherlands vs S-formula: 0.02±0.6 g/kg/24 h) resulting from are impaired intracellular insulin signalling, 2 7Department of Paediatrics, signifi cantly increased protein synthesis (PE-formula: impaired glucose uptake 3 and reduced mitochon- Emma Children’s Hospital- 4 AMC, Amsterdam, the 9.6±4.4, S-formula: 5.2±2.3 g/kg/24 h), despite drial capacity during critical illness. These fac- Netherlands signifi cantly increased protein breakdown (PE-formula: tors are probably the reason why protein-energy 8 Department of Paediatrics, 8.9±4.3, S-formula: 5.2±2.6 g/kg/24 h). SPE Phe was malnutrition is observed in 16–24% of critically ill ErasmusMC-Sophia Children’s not statistically different between the two groups children 5 6 and is associated with adverse clinical on September 24, 2021 by guest. Protected copyright. Hospital, Rotterdam, the (PE-formula: 39.8±18.3%, S-formula: 52.4±13.6%). outcome. 7 – 9 Netherlands C o n c l u s i o n s Increasing protein and energy intakes A common but threatening disease in infants is Correspondence to promotes protein anabolism in critically ill infants in the viral bronchiolitis, which in severe cases leads to Dick A van Waardenburg, fi rst days after admission. Since this is an important respiratory failure with need for ventilatory sup- Department of Paediatrics, target of nutritional support, increased protein and port and PICU admission. Adequate nutritional Maastricht University Medical Center, PO Box 5800, 6202 AZ energy intakes should be preferred above standard support in these critically ill infants is important, Maastricht, The Netherlands; intakes in these infants. with protein anabolism as goal. However, up to d . v a n w a a r d e n b u r g @ m u m c . n l Dutch Trial Register number: NTR 515. now common practice has been to use standard C T de Betue and D A van infant formulas to provide approximately 1.5 g Waardenburg are joint fi rst protein/kg/day and 100 kcal/kg/day. authors I N T R O D U C T I O N Increased protein intake with adequate The preservation of nutritional status and growth energy provision promotes anabolism in pre- Accepted 27 April 2011 is a specifi c aim in critically ill children, but dif- term infants, 10 – 12 in neonates undergoing sur- fi cult to achieve. This is due to a metabolic stress gery 13 and in children with burns14 and cystic response with profound changes in protein metab- fi brosis. 15 In relation to these observations, it olism leading to a negative protein balance and loss is important to note that protein synthesis is a of lean body mass. Inadequate nutritional intake high-energy consuming process 16 and energy in the paediatric intensive care unit (PICU), often defi ciency worsens nitrogen balance. 17 18 Hence, due to fl uid restriction, further leads to protein to induce net protein anabolism, it is essential to and energy defi cits, especially early after admis- provide an adequate energy intake. We therefore sion. 1 Other factors that hinder adequate nutrition hypothesised that increasing protein and energy Copyrightde Betue CT,Article van Waardenburg author DA, (or Deutz their NE, etemployer) al. Arch Dis Child 2011. (2011). Produceddoi:10.1136/adc.2010.185637 by BMJ Publishing Group Ltd (& RCPCH) under 1licence. of 6 Original article Arch Dis Child: first published as 10.1136/adc.2010.185637 on 14 June 2011. Downloaded from intakes would induce net protein anabolism in critically ill continuous enteral feeding with PE-formula (Infatrini: 2.6 g infants. protein/100 ml, 100 kcal/100 ml) or with S-formula (Nutrilon 1: Stable isotope amino acid methods are used to determine net 1.4 g protein/100 ml, 67 kcal/100 ml) both from Nutricia protein balance. 19 During feeding, amino acids appearing in Advanced Medical Nutrition, Zoetermeer, The Netherlands. the circulation originate from protein breakdown and from the Compositions are summarised in appendix 1. Formulas were fraction of meal-derived amino acids that are not retained in the administered as previously described, starting 25.3±5.6 versus splanchnic area. Protein synthesis during feeding can be calcu- 23.4±5.4 h after PICU-admission in the PE-group and S-group, lated from the disappearance of essential amino acids (EAAs) respectively. 22 The ranges of protein and energy intakes on such as phenylalanine from the circulation, corrected for non- day 5 in the S-group (1.7±0.2 g protein/kg/24 h, 84±15 kcal/ protein synthesis related disposal (eg, oxidation, hydroxyla- kg/24 h) covered recommended intakes for healthy infants tion). Therefore, all these factors need to be considered if whole <6 months (1.14–1.77 g protein/kg/24 h, 81–113 kcal/kg/24 h, body net protein anabolism during feeding is to be calculated.20 depending on age in months). 16 25 The ranges were signifi cantly 21 Splanchnic extraction (SPE) of meal-derived amino acids has higher in the PE-group (3.1±0.3 g protein/kg/24 h, p<0.001; not been reported before in critically ill children. 119±25 kcal/kg/24 h, p<0.001) and were 175–272% and The present study was part of a larger study on the nutritional 105–147% of recommended intakes for protein and energy, and metabolic effects of increased protein and energy intakes respectively. Intake by volume was not signifi cantly different using a protein and energy enriched formula (PE-formula) between groups; 120.6±13.4 ml/kg/24 h in the PE-group versus compared with a standard infant formula (S-formula). 22 In the 118.5±13.4 ml/kg/24 h in the S-group.
Load more

Recommended publications
  • 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]
  • Citric Acid Cycle
    CHEM464 / Medh, J.D. The Citric Acid Cycle Citric Acid Cycle: Central Role in Catabolism • Stage II of catabolism involves the conversion of carbohydrates, fats and aminoacids into acetylCoA • In aerobic organisms, citric acid cycle makes up the final stage of catabolism when acetyl CoA is completely oxidized to CO2. • Also called Krebs cycle or tricarboxylic acid (TCA) cycle. • It is a central integrative pathway that harvests chemical energy from biological fuel in the form of electrons in NADH and FADH2 (oxidation is loss of electrons). • NADH and FADH2 transfer electrons via the electron transport chain to final electron acceptor, O2, to form H2O. Entry of Pyruvate into the TCA cycle • Pyruvate is formed in the cytosol as a product of glycolysis • For entry into the TCA cycle, it has to be converted to Acetyl CoA. • Oxidation of pyruvate to acetyl CoA is catalyzed by the pyruvate dehydrogenase complex in the mitochondria • Mitochondria consist of inner and outer membranes and the matrix • Enzymes of the PDH complex and the TCA cycle (except succinate dehydrogenase) are in the matrix • Pyruvate translocase is an antiporter present in the inner mitochondrial membrane that allows entry of a molecule of pyruvate in exchange for a hydroxide ion. 1 CHEM464 / Medh, J.D. The Citric Acid Cycle The Pyruvate Dehydrogenase (PDH) complex • The PDH complex consists of 3 enzymes. They are: pyruvate dehydrogenase (E1), Dihydrolipoyl transacetylase (E2) and dihydrolipoyl dehydrogenase (E3). • It has 5 cofactors: CoASH, NAD+, lipoamide, TPP and FAD. CoASH and NAD+ participate stoichiometrically in the reaction, the other 3 cofactors have catalytic functions.
    [Show full text]
  • Biochemistry Anabolism of Lipids
    Paper : 05 Metabolism of Lipids Module: 12 Anabolism of Lipids Principal Investigator Dr. Sunil Kumar Khare, Professor, Department of Chemistry, IIT-Delhi Dr. Vijaya Khader Dr. MC Varadaraj Paper Coordinator and Dr. Suaib Luqman, Scientist (CSIR-CIMAP) Content Writer & Assistant Professor (AcSIR) CSIR -CIMAP, Lucknow Content Reviewer Prof. Prashant Mishra, Professor, Department of Biochemical Engineering and Biotechnology, IIT-Delhi 1 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids DESCRIPTION OF MODULE Subject Name Biochemistry Paper Name 05 Metabolism of Lipids Module Name/Title 12 Lipids-Anabolism 2 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 1. Objectives To understand the anabolism of lipids What are the implications of lipid anabolism 2. Concept Map 3 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 4 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 3. Description Anabolism is the word derived from the Greek (Ana-upward and Bolism-to throw) meaning a process that have a propensity to build up tissues and organs. It is an array of metabolic pathways that assemble molecules from smaller units and the process engender differentiation and growth of cells and augmentation in body size (e.g. growth and mineralization of bone and increase in muscle mass). The reactions in anabolism entail and utilize energy released by catabolism to synthesize complex molecules which further employed to form cellular 5 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids structures from simple and small precursors that act as building blocks. Numerous anabolic processes are power- driven by the hydrolysis of adenosine triphosphate (ATP). Following are the fundamental defined stages of anabolism. 1. Assembly of precursors such as fatty acids, amino acids, isoprenoids, monosaccharides and nucleotides.
    [Show full text]
  • ANABOLISM III: Biosynthesis Amino Acids & Nucleotides
    BI/CH 422/622 ANABOLISM OUTLINE: Photosynthesis Carbohydrate Biosynthesis in Animals Biosynthesis of Fatty Acids and Lipids Biosynthesis of Amino Acids and Nucleotides Nitrogen fixation nitrogenase Nitrogen assimilation Glutamine synthetase Glutamate synthase Amino-acid Biosynthesis non-essential essential Nucleotide Biosynthesis RNA precursors purines pyrimidines DNA precursors deoxy-nucleotides Biosynthesis of secondary products of amino acids ANABOLISM III: Biosynthesis Amino Acids & Nucleotides Dr. Kornberg: Lecture 04.26.17 (0:00-5:06) 5 min 1 Biosynthesis Amino Acids & Nucleotides How are Ribonucleic Acid Precursors So far: converted to Deoxyribonucleic Acid GMPàGDPàGTP Precursors? ….....and how is dTTP made? AMPàADPàATP 2’C-OH bond is directly reduced to 2’-H UMPàUDPàUTPà bond …without activating the carbon for CDPßCTP dehydration, etc.! catalyzed by ribonucleotide reductase Specific kinases, Non-specific kinase, e.g., UMP kinase, nucleoside GMP kinase, diphosphate kinase Very unique enzyme in all of biochemistry – use of free Adenylate kinase (works on both oxy- and radicals etc. deoxy-ribose GDPàdGDP nucleosides) Mechanism: Two H atoms are donated ADPàdADP by NADPH and carried by thioredoxin or glutaredoxin to the active site. UDPàdUDP –Substrates are the NDPs and the products CDPàdCDP are dNDP. Biosynthesis Amino Acids & Nucleotides Source of Reducing Structure of Ribonucleotide Reductase a2 are regulatory Electrons for and half the Ribonucleotide catalytic site; need to be reduced. Reductase b 2 are the other half (a b ) of the active site, 2 2 and the free- radical generators • NADPH serves as the electron donor. • Funneled through glutathione or JoAnne Stubbe thioredoxin pathways (1946– ) 2 •Most forms of enzyme have two catalytic/ regulatory subunits and two radical- generating subunits.
    [Show full text]
  • Metabolism Unit III Lipid Anabolism (MSLSC2001C04)
    Metabolism MSLSC2001C04 Course Instructor Dr. Gautam Kumar Dr. Gautam Kr. Dept. of Life Sc 1 Dr. Gautam Kr. Dept. of Life Sc 2 Lipids Metabolism • Lipids are the principal form of stored energy in most organisms and major constituents of cellular membranes. • Specialized lipids serve as pigments (retinal, carotene) cofactors (vitamin K), detergents (bile salts), transporters (dolichols), hormones (vitamin D derivatives, sex hormones), extracellular and intracellular messengers (eicosanoids, phosphatidylinositol derivatives), and anchors for membrane proteins (covalently attached fatty acids, prenyl groups, and phosphatidylinositol). • Water-insoluble products from water-soluble precursors such as Acetate. • During Fatty acids synthesis ATP as a source of metabolic energy and a reduced electron carrier (usually NADPH). Dr. Gautam Kr. Dept. of Life Sc 3 Lipid Metabolism • Fatty acid synthesis takes place in the compartment in which NADPH is available for reductive synthesis (i.e., where the [NADPH]/[NADP] ratio is high) Subcellular localization of lipid metabolism Dr. Gautam Kr. Dept. of Life Sc 4 Acetyl-CoA Shuttle • Shuttle for transfer of AcetylDr.- GautamCoA Kr.groups Dept. of Life from Sc mitochondria to the cytosol5 • The mitochondrial outer membrane is freely permeable to all these compounds. • Pyruvate derived from amino acid catabolism in the mitochondrial matrix, or from glucose by glycolysis in the cytosol, is converted to acetyl-CoA in the matrix. • Acetyl groups pass out of the mitochondrion as citrate; in the cytosol they are delivered as acetyl-CoA for fatty acid synthesis. • Oxaloacetate is reduced to malate, which returns to the mitochondrial matrix and is converted to oxaloacetate. • Cytosolic malate is oxidation by malic enzyme to generate cytosolic NADPH; the pyruvate produced returns to the mitochondrial matrix.
    [Show full text]
  • Insulin Resistance of Protein Anabolism Accompanies That of Glucose Metabolism in Lean, Glucose-Tolerant Offspring of Persons with Type 2 Diabetes
    BMJ Open Diab Res Care: first published as 10.1136/bmjdrc-2016-000312 on 29 November 2016. Downloaded from Open Access Research Insulin resistance of protein anabolism accompanies that of glucose metabolism in lean, glucose-tolerant offspring of persons with type 2 diabetes Sergio A Burgos,1,2 Vikram Chandurkar,3 Michael A Tsoukas,1 Stéphanie Chevalier,1 José A Morais,1 Marie Lamarche,1 Errol B Marliss1 To cite: Burgos SA, ABSTRACT Significance of this study Chandurkar V, Tsoukas MA, Objective: To test whether protein anabolic resistance et al . Insulin resistance of is an early defect in type 2 diabetes (T2D). protein anabolism What is already known about this subject? accompanies that of glucose Research design and methods: Seven lean, ▪ The offspring of patients with type 2 diabetes are metabolism in lean, glucose- normoglycemic T2D offspring (T2D-O) and eight at a higher risk of developing the disease. tolerant offspring of persons matched participants without family history (controls; ▪ 2 Previous studies have identified several abnor- with type 2 diabetes. BMJ C) underwent a 3-hour hyperinsulinemic (40 mU/m / malities in glucose and lipid metabolism in this Open Diabetes Research and min), euglycemic (5.5 mmol/L) and isoaminoacidemic population, but the status of protein metabolism Care 2016;4:e000312. clamp. Whole-body glucose and protein kinetics were 3 13 is not known. doi:10.1136/bmjdrc-2016- measured with D-[3– H]glucose and L-[l- C]leucine, 000312 respectively. Plasma amino acids were measured by What are the new findings? liquid chromatography-tandem mass spectrometry. ▪ The main finding of the study is the presence of Results: Fasting glycemia and glucose kinetic altered protein metabolism in lean young off- ▸ Additional material is variables did not differ between groups.
    [Show full text]
  • The Role of Mitochondrial Fat Oxidation in Cancer Cell Proliferation and Survival
    cells Review The Role of Mitochondrial Fat Oxidation in Cancer Cell Proliferation and Survival Matheus Pinto De Oliveira 1,2,3 and Marc Liesa 1,2,3,* 1 Department of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; [email protected] 2 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA 3 Molecular Biology Institute at UCLA, Los Angeles, CA 90095, USA * Correspondence: [email protected]; Tel.: +1-310-206-7319 Received: 3 October 2020; Accepted: 2 December 2020; Published: 4 December 2020 Abstract: Tumors remodel their metabolism to support anabolic processes needed for replication, as well as to survive nutrient scarcity and oxidative stress imposed by their changing environment. In most healthy tissues, the shift from anabolism to catabolism results in decreased glycolysis and elevated fatty acid oxidation (FAO). This change in the nutrient selected for oxidation is regulated by the glucose-fatty acid cycle, also known as the Randle cycle. Briefly, this cycle consists of a decrease in glycolysis caused by increased mitochondrial FAO in muscle as a result of elevated extracellular fatty acid availability. Closing the cycle, increased glycolysis in response to elevated extracellular glucose availability causes a decrease in mitochondrial FAO. This competition between glycolysis and FAO and its relationship with anabolism and catabolism is conserved in some cancers. Accordingly, decreasing glycolysis to lactate, even by diverting pyruvate to mitochondria, can stop proliferation. Moreover, colorectal cancer cells can effectively shift to FAO to survive both glucose restriction and increases in oxidative stress at the expense of decreasing anabolism.
    [Show full text]
  • Glycolytic Reliance Promotes Anabolism in Photoreceptors
    bioRxiv preprint doi: https://doi.org/10.1101/101964; this version posted January 21, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Glycolytic reliance promotes anabolism in photoreceptors Yashodhan Chinchore, Tedi Begaj, David Wu, Eugene Drokhlyansky, Constance L. Cepko* *Departments of Genetics and Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA [email protected] bioRxiv preprint doi: https://doi.org/10.1101/101964; this version posted January 21, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Sensory neurons capture information from the environment and convert it 2 into signals that can greatly impact the survival of an organism. These systems 3 are thus under heavy selective pressure, including for the most efficient use of 4 energy to support their sensitivity and efficiency1. In this regard, the 5 vertebrate photoreceptor cells face a dual challenge. They not only need to 6 preserve their membrane excitability via ion pumps by ATP hydrolysis2 but 7 also maintain a highly membrane rich organelle, the outer segment, which is 8 the primary site of phototransduction, creating a considerable biosynthetic 9 demand. How photoreceptors manage carbon allocation to balance their 10 catabolic and anabolic demands is poorly understood. One metabolic feature 11 of the retina is its ability to convert the majority of its glucose into lactate3,4 12 even in the presence of oxygen.
    [Show full text]
  • Nonenzymatic Gluconeogenesis-Like Formation of Fructose 1,6-Bisphosphate in Ice
    Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice Christoph B. Messnera,b, Paul C. Driscollc, Gabriel Piedrafitab,d, Michael F. L. De Voldere, and Markus Ralsera,b,1 aThe Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom; bDepartment of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, United Kingdom; cMetabolomics Science Technology Platform, The Francis Crick Institute, London NW1 1AT, United Kingdom; dWellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom; and eDepartment of Engineering, Institute for Manufacturing, University of Cambridge, Cambridge CB3 0FS, United Kingdom Edited by David W. Russell, University of Texas Southwestern Medical Center, Dallas, TX, and approved June 6, 2017 (received for review February 10, 2017) The evolutionary origins of metabolism, in particular the emergence To support life, cellular metabolism depends on the parallel oc- of the sugar phosphates that constitute glycolysis, the pentose currence of anabolism and catabolism. Otherwise, metabolism phosphate pathway, and the RNA and DNA backbone, are largely would cease once the thermodynamic equilibrium, to which chem- unknown. In cells, a major source of glucose and the large sugar ical networks evolve, is reached (typically the point where all avail- phosphates is gluconeogenesis. This ancient anabolic pathway able substrates are consumed). In enzyme-catalyzed metabolism, the (re-)builds carbon bonds as cleaved in glycolysis in an aldol conden- simultaneous occurrence of catabolic and anabolic reactions is sation of the unstable catabolites glyceraldehyde 3-phosphate and achieved by coupling the primary metabolic reaction to secondary dihydroxyacetone phosphate, forming the much more stable fructose reactions, coenzyme functions, or active membrane transport pro- 1,6-bisphosphate.
    [Show full text]
  • Glycogen Glycogen –12 Topics Carbohydrate Metabolism Investing for the Future Outline of Topics
    Carbohydrate Storage and Synthesis in Liver and Muscle: Glycogen Glycogen –12 topics Carbohydrate Metabolism Investing for the future Outline of Topics Glucose Fuel Storage and mobilization for oxidaton . Introduction . Structure of Glycogen –highly branced ‐glucose polymer . Glycogenesis – Glc incorporated into glycogen (liver & muscle, kidney) . Glycogenolysis –Glucose mobilized from glycogen in liver and muscle . Hormonal regulation of hepatic glycogenesis vs. glycogenolysis – insulin vs. glucagon . Mechanisms of glucagon action – Signals phosphorylations, pathways flip . Glycogenolysis in liver –plasma glycemia maintenance: acute vs. postabsorbtive . Glycogenolysis in muscle – Mobilizing glucose for ATP contraction activity . Regulation of glycogenesis –replenish glycogen stores vs. immediate needs . GluconeogenesisGluconeogenesis – de novo (new) glucose from non carbohydrate carbon skeletons . Regulation of gluconeogenesis –De novo glucose synthesis fueled by fat oxidation . Interconversions of fructose/galactose/mannose/glucose – glycoproteins, etc., … . Inborn errors of metabolism – glycogen storage diseases 2 Metabolic Fate of Glucose Glycogen Metabolism Introduction . Red cells and the brain –Have an absolute requirement for blood glucose for their energy metabolism. These cells consume about 80% of the glucose (200 g, 1.1 mol, ca. 1500 kcal) consumed per day by a 70 kg human, in good health. Blood and extracellular fluid volume contains about 10 g glucose –must be replenished constantly. Assumes a blood volume = 7 L, hematocrit = 45%, and no other distribution system operates. Normally, blood [glucose] range is between 4 –6.5 mM = glycemia (about 80 – 120 mg/dL) 3 Hypoglycemia – hyperglycemia ‐ glycemia Glycogen Metabolism [glucose], in blood plasma Introduction Prandial (meal): preprandial, postprandial, … postabsorptive Before meal . hypoglycemia (4–2.5 mM, 45 mg/dL); . extreme hypoglycemia, <2.5 mM, life‐threatening hypoglycemia rapidly compromises brain function, leading to confusion and disorientation.
    [Show full text]
  • 1-Glycogen Metabolism
    Glycogen Metabolism – Color Index: § Important. § Extra Information. 436 Biochemistry team § Doctors slides. Objectives: By the end of the lecture. Students should be familiar with : u The need to store carbohydrates in muscle u The reason for carbohydrates to be stored as glycogen u An overview of glycogen synthesis (Glycogenesis) u An overview of glycogen breakdown (Glycogenolysis) u Key elements in regulation of both Glycogenesis and Glycogenolysis (this objective is important for other lectures) Glycogen Metabolism Remember metabolism is a mixed up between catabolism and anabolism u Glycogen: is a branched – chain homopolysaccharide of glucose that serves as a form of energy storage made from α -D-Glucose u Glycogen could be found in all types of cells, but in very small amounts (traces of glycogen), the main stores of glycogen are found in skeletal muscle and liver. Metabolism of Glycogen in Skeletal Muscle: 1- Glycogenesis:(Anabolism) 2- Glycogenolysis :(catabolism) Synthesis of Glycogen from Breakdown of Glycogen to glucose Glucose-6-phosphate Structure of Glycogen N.B. *All glucose residues in human Bonds in Glycogen are alpha. The primary glycosidic bond is After 8 to 10 residues there is a α (1à4) Glycosidic linkage branch containing α ( 1à6 ) Between glucose residues Glycosidic linkage (linear ) o These polymers of glucose (Glycogen) exist in which contain most of the ﺣﺒﯿﺒﺎت cytoplasmic granules enzymes necessary for glycogen synthesis and degradation . Residue is a partial of UDP-Glucose *ﻛﻞ وﺣﺪة ﻣﻦ اﻟﺮواﺑﻂ ﻋﻨﺪھﺎ اﻧﺰﻳﻢ ﻣﻤﯿﺰ ﻳﻜﻮﻧﮫﺎ وﻳﻔﻜﮫﺎ Glycogen Structure α (1-4) Glycosidic linkage Between the glucose residues Why is glycogen a branched-chain ? α ( 1-6 ) Glycosidic linkage In Branches To contain high number of homopolysaccharides within a small space.
    [Show full text]
  • Regulation of Cellular Respiration Heyer 1
    Regulation of Cellular Respiration Uncoupling Proteins Uncoupling proteins (UCP) in inner mitochondrial membrane of mammals Allow some H+ leakage, bypassing ATP-synthase. Metabolic . Burn fuel stores without generating ATP . May be important in regulating %body fat Pathways: . May also be important in reducing formation of dangerous Reactive Oxygen Species (ROS) + – . H -leakage is activated by O2 . a summary – + 1 . O2 + 2H → H2O2 → H2O + /2O2 In brown (thermogenic) fat, UCP1 causes heat generation by burning high-caloric lipid fuel without producing ATP High activity tissues [skeletal muscle] have high ATP demand. But since [ATP] would inhibit ATP synthesis — — cannot “store” excess ATP reserve. • Exchange –P of ATP to P–Creatine • Exchange back to ATP from P–Cr at myofibrils ⇑⇑ATP→ inhibits F-6-P-kinase ∴ F-6-P → back to G-6-P Creatine → alternate pathway → G-1-P Kinase → glycogenesis ⇑⇑ATP→ inhibits Krebs Cycle enzymes CK CK ∴ acetyl-CoA → alternate pathway → fatty acid synthesis → lipogenesis Cellular Cellular Metabolism 1. Metabolism Glucose-6-Phosphate Glucose Glucose-6-Phosphate Glucose 2. 2. 5. 3. Catabolic pathways: 6. 1. Glycogenolysis 7. 2. Glycolysis 3. Pyruvate Oxidation 4. Krebs Cycle 4. 5. Lipolysis 4. 6. ß- Oxidation = hepatocytes only! 7. Proteolysis Heyer 1 Regulation of Cellular Respiration Cellular Metabolism Cellular Metabolism 2. 1. Glucose-6-Phosphate Glucose Glucose-6-Phosphate Glucose 1. 4. 2. 6. Anabolic pathways: 3. 5. 1. Gluconeogenesis 3. 2. Glycogenesis Intermediate pathways: 3. Fatty Acid Synthesis 1. Glucophosphatase 4. Lipogenesis 2. Pyruvate Reduction/ 5. Ketogenesis Lactate Oxidation = hepatocytes only! = hepatocytes only! 6. Translation 3. Deamination Glycogenesis and Glycogenolysis Uses of Different Energy Sources • Glucose-6-phosphate cannot leak out of the cell.
    [Show full text]