DOCSLIB.ORG

Overview of Gluconeogenesis, and Pentose Phosphate Pathway

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Overview of Gluconeogenesis, and Pentose Phosphate Pathway Biochemistry I Overview of Gluconeogenesis, and Pentose Phosphate Pathway Cori Cycle Gluconeogenesis Chapter 16 – part 3 Covered on Exam 3 (includes material from Chapter 20, p.589-590) Dr. Ray Control of Glycolysis • The flux through the glycolytic pathway must 1 be adjusted in response to conditions both inside and outside the cell. The rate of 2 conversion of glucose into pyruvate is regulated to meet two major cellular needs: 3 1) the production of ATP, generated by the 4 degradation of glucose 2) the provision of building blocks for 5 synthetic reactions, such as the formation of fatty acids. 6 In metabolic pathways, enzymes catalyzing essentially irreversible 7 reactions are potential sites of control. 8 1. Which glycolytic enzymes are likely to be sites of control? 9 The ________________ reactions at steps __________ , which is 10 near equilib in cellular concentrations) Energetics of Glycolysis • Most of the decrease in free energy in glycolysis takes place in the three essentially irreversible steps catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase. step ? 1 3 10 • The energy released in the anaerobic conversion of glucose into two molecules of pyruvate is only a portion of the total energy captured during complete aerobic glucose catabolism. 2. Where does most of the rest of the energy capture occur? 3. If glucose needed to be made, which steps would require the most amount of energy to overcome? http://higheredbcs.wiley.com/legacy/college/boyer/0471661791/animations/animations.htm Introduction to Metabolism Traits of Metabolism Gluconeogenesis Focus on comparing Gluconeogenesis to Glycolysis • The synthesis of glucose from non-carbohydrate precursors (such as pyruvate and lactate) is called gluconeogenesis. 1. Why is this metabolic pathway important? because the _______ depends on glucose as its primary fuel and _______________ use only glucose as a fuel Red Blood Cells do not have mitochondria, so they do not do aerobic metabolism. All ATP is made only from glycolysis. • The daily glucose requirement of the brain in a typical adult human being is about 120 g, which accounts for most of the 160 g of glucose needed daily by the whole body. • The amount of glucose present in body fluids is about 20 g, and that readily available from glycogen, a storage form of glucose, is approximately 190 g. •Thus, the direct glucose reserves are sufficient to meet glucose needs for about a day. During a longer period of not eating, glucose must be formed from non-carbohydrate sources, through gluconeogenesis. http://higheredbcs.wiley.com/legacy/college/boyer/0471661791/ animations/animations.htm Glycolysis and Hexokinase 1 Gluconeogenesis 2 • Under typical cellular conditions, most of the decrease in free energy in Phosphofructo 3 kinase glycolysis takes place in the 4 three essentially irreversible steps catalyzed by: (1) hexokinase 5 (3) phosphofructokinase 6 (10) pyruvate kinase • In gluconeogenesis, these 7 three irreversible steps are by-passed by other reactions, 8 in order to overcome the energetic barrier. 9 • Gluconeogenesis is energetically costly. Pyruvate 10 kinase http://higheredbcs.wiley.com/legacy/college/boyer/ 0471661791/animations/animations.htm Text Fig 16.2 Gluconeogenesis Energetics Gluconeogenesis is not the Reverse of Glycolysis DG’ for the formation of pyruvate from glucose (in glycolysis) is about -84 kJ/mol 1 3 10 Unique Reactions of Gluconeogenesis: In gluconeogenesis, the three irreversible steps above are by-passed by other unique reactions, in order to overcome the energetic barrier. Replace step 10 (with 2 steps) Replace step 3: Replace step 1: Energetics of Gluconeogenesis in glycolysis (step 3 - kinase) DGo’ = -14.2 kJ/mol in gluconeogenesis DGo’ = -16.3 kJ/mol (step 8 - phosphatase) Exergonic hydrolysis catalyzed by Fructose 1,6-bisphosphatase Both kinase and phosphatase reactions are exergonic. Kinase uses ATP for phosphate source and for energy source . Phosphatases hydrolyze phosphorylated alcohols (ROP), which have some What is the phosphoryl transfer potential small amount of free of Pi (inorganic phosphate? energy of hydrolysis. Gluconeogenesis - NOT a reversal of glycolysis The three exergonic (irreversible) steps of glycolysis in cell: (1) Hexokinase phosphorylate (2) Phosphofructokinase (3) Pyruvate kinase Substrate level phosphorylation are replaced by other favorable reactions: dephosphorylate (1) Glucose-6-phosphatase (2) Fructose-1,6-bisphosphatase Pyruvate Oxaloacetate PEP (3a) Pyruvate carboxylase (3b) Phosphoenolpyruvate carboxykinase (reactions 3a & 3b) know overview only, NO details Gluconeogenesis vs. Reversal of Glycolysis The stoichiometry of gluconeogenesis is: Gluconeogenesis costs 6 ATP equivalents In contrast, the stoichiometry for the reversal of glycolysis is: Glycolysis produces 2 ATP DGo’ = - 84 kJ/mol Overall, both pathways are highly exergonic (spontaneous)! Recall that one ATP equivalent changes the equilibrium constant by a factor of about 108. Hence, the input of four additional high-energy bonds in Gluconeogenesis changes the equilibrium by a factor of about 1032. This is a clear example of the coupling of reactions: ATP hydrolysis is used to power an energetically unfavorable reaction. Non-carbohydrate Precursors of Gluconeogenesis • Lactate – formed by lactate dehydrogenase in active skeletal muscle when rate of glycolysis exceed rate of oxidative metabolism (because of insufficient levels of oxygen). • Amino acids – from proteins in the diet and during starvation from breakdown of proteins in skeletal muscle. • Glycerol – from hydrolysis of triacylglycerols in fat cells. Glycerol can enter the glycolytic or gluconeogenic pathways through DHAP: Phosphorylate at C3 Oxidize at C2 - is used Comparison of Glycolysis & Gluconeogenesis + is made Glycolysis makes 2 ATP Gluconeogenesis costs 6 ATP (1) Hexokinase (- ATP) (11) Glucose-6-phosphatase (9) Fructose-1,6-bisphosphatase (3) Phosphofructokinase (- ATP) (1) Pyruvate carboxylase (- ATP) and (10) Pyruvate kinase (+ ATP) (2) Phosphoenolpyruvate carboxykinase (- GTP) (7) Phosphoglycerate kinase (+ATP) (5) Phosphoglycerate kinase (-ATP) happens twice In most tissues gluconeogenesis stops after formation of glucose-6-phosphate, which can be stored as glycogen. One advantage to ending gluconeogenesis at glucose 6-phosphate is that, unlike free glucose, the molecule cannot diffuse out of the cell. To keep glucose inside the cell, the generation of free glucose is controlled in two ways: 1. Enzyme responsible for the conversion of glucose 6-phosphate into glucose, glucose 6-phosphatase, is regulated. 2. Enzyme is present only in tissues whose metabolic duty is to maintain blood-glucose homeostasis. Tissues that release glucose into the blood are the liver and to lesser extent the kidney. Gluconeogenesis Glycolysis and Gluconeogenesis are coordinated, in a tissue- specific fashion, to ensure that the glucose-dependent energy needs of ALL cells are met. In a particular cell, when one pathway is upregulated, the other is downregulated. Reciprocal regulation • The main site of gluconegenesis is Cori Cycle (Figure 16.33) in the liver, with a small amount occurring in the kidneys. • Gluconeogenesis in these two organs helps maintain glucose levels in the blood so that the brain, red blood cells and muscles can extract sufficient glucose from blood to satisfy their energy needs. http://www.wiley.com/college/fob/quiz/quiz21/21-5.html The Cori Cycle CORI CYCLE - Lactate formed by active muscle travels through the blood and is converted into glucose by the liver. This cycle shifts part of the metabolic burden of active muscle to the liver. Cori Cycle (Figure 16.33) Lactate Dehydrogenase (LDH) Isozymes: H4, H3M1, H2M2, H1M3, M4 H = heart (higher affinity for lactate) takes in lactate, oxidizes it to pyruvate, then uses pyruvate via aerobic metabolism (citric acid cycle, electron transport chain) M = skeletal muscle and liver, have lower affinity for lactate In the liver, lactate is oxidized to pyruvate by lactate dehydrogenase. This pyruvate undergoes gluconeogenesis to produce free glucose, which is released into the blood. The liver restores the level of glucose necessary for active muscle cells to continue anaerobic glycolysis for immediate energy needs. Carbohydrate Metabolism and the Liver Workbook, Chapter 16 Self-Test, Q27: 1. Which of the following statements about the Cori cycle and its physiologic consequences are true? A) It involves the synthesis of glucose in muscle. B) It involves release of lactate by muscle. C) It involves lactate synthesis in the liver. Anaerobic glycolysis in D) It involves ATP synthesis in muscle. muscle E) It involves release of glucose by the liver. 2. How much energy is extracted when one glucose is converted to 2 pyruvate? 3. What is the energy cost of producing one glucose from 2 pyruvate? Gluconeogenesis in liver Other Metabolic Pathways Associated with Glycolysis • The entry point of other important dietary Glycogen Energy Storage sugars into glycolysis varies with the monosaccharide and Pentose Phosphate Pathway the organ. PFK Biosynthesis • Common entry points NADPH are: Glucose-6-P and Growth Fructose-6-P ribose-5-phosphate DHAP & GAP GLYCOGEN FRUCTOSE hexokinase DHAP O Phospho- Isomeri- Phospho- O O H O rylation H zation rylation CH2 O P O- C C CH2OH CH2 O P O- O O- H OH H OH O O O- CH OH HO H HO H HO H PFK HO H 2 O H H OH hexo- H OH H OH H OH C H OH kinase H OH O H OH O H OH O H OH O CH OH CH O P O- 2 CH2 O P O- 2 CH2 O P O- CH2 O P O- O- O- O- O- Glucose G6P F6P FBP GAP Multiple Fates of Glucose-6-Phosphate (G6P) from Introduction to Chapter 20 (p. 589 – 590) 1. Used as fuel in anaerobic or Figure 21.3 aerobic glycolysis 2. Converted to free gluocose by liver and released into the blood to raise blood sugar when too low 3. Processed by Pentose Phosphate Pathway, which produces: • 5C Ribose (for DNA/RNA synthesis) and • NADPH (for reductive biosynthesis of biomolecules) First stage of PPP: http://www.wiley.com/college/fob/quiz/quiz15/15-1.html Pentose Phosphate Pathway – Needed for Biosynthesis Anabolism is REDUCTIVE so biosynthesis and growth require the reduced cofactor __________ , which is produced by the pentose phosphate pathway.
Load more

Recommended publications
  • Cori Cycle Activity in Man
    Cori cycle activity in man Christine Waterhouse, Julian Keilson J Clin Invest. 1969;48(12):2359-2366. https://doi.org/10.1172/JCI106202. Research Article 12 subjects have been studied after an overnight fast with trace amounts of pyruvate-3-14C and glucose-6-14C. Blood disappearance curves and incorporation of the pyruvate-3-14C label into blood glucose have been determined. By the use of transfer functions which allow processes with many different chemical steps to be examined as a unit, we have determined the per cent of pyruvate and presumably lactate which is regenerated into glucose. 8 of the 12 subjects showed that 7-23 mg/kg per hr are recycled, while 4 subjects fell well outside this range. Correlation of increased activity was not good with any demonstrated metabolic abnormality (diabetes or obesity), and it is suggested from clinical observation of the subjects that anxiety may play a role. Find the latest version: https://jci.me/106202/pdf Cori Cycle Activity in Man CHRISTIE WATERHOUSE and JULLAN KEISON From the Department of Medicine, University of Rochester School of Medicine and Dentistry and the Department of Statistics, University of Rochester College of Arts and Sciences, Rochester, New York 14620 ABSTRACT 12 subjects have been studied after an glucose derived from lactate and pyruvate. The analysis overnight fast with trace amounts of pyruvate-3-'4C and itself also views glucose as distributed in a homogeneous glucose-6-'4C. Blood disappearance curves and incorpora- pool within the body, thus neglecting the early portion tion of the pyruvate-3-14C label into blood glucose have of the glucose 'C disappearance curve.
    [Show full text]
  • Glycolysis and Gluconeogenesis
    CC7_Unit 2.3 Glycolysis and Gluconeogenesis Glucose occupies a central position in the metabolism of plants, animals and many microorganisms. In animals, glucose has four major fates as shown in figure 1. The organisms that do not have access to glucose from other sources must make it. Plants make glucose by photosynthesis. Non-photosynthetic cells make glucose from 3 and 4 carbon precursors by the process of gluconeogenesis. Glycolysis is the process of enzymatic break down of one molecule of glucose (6 carbon) into two pyruvate molecules (3 carbon) with the concomitant net production of two molecules of ATP. The complete glycolytic pathway was elucidated by 1940, largely through the pioneering cotributions of Gustav Embden, Otto Meyerhof, Carl Neuberg, Jcob Parnad, Otto Wrburg, Gerty Cori and Carl Cori. Glycolysis is also known as Embden-Meyerhof pathway. • Glycolysis is an almost universal central pathway of glucose catabolism. • Glycolysis is anaerobic process. During glycolysis some of the free energy is released and conserved in the form of ATP and NADH. • Anaerobic microorganisms are entirely dependent on glycolysis. • In most of the organisms, the pyruvate formed by glycolysis is further metabolised via one of the three catabolic routes. 1) Under aerobic conditions, glucose is oxidized all the way to C02 and H2O. 2) Under anaerobic conditions, the pyruvic acid can be fermented to lactic acid or to 3) ethanol plus CO2 as shown in figure 2. • Glycolytic breakdown of glucose is the sole source of metabolic energy in some mammalian tissues and cells (RBCs, Brain, Renal medulla and Sperm cell). Glycolysis occurs in TEN steps.
    [Show full text]
  • 8. 2020-New METABOLISM in CANCER CELLS-Students
    METABOLIC ALTERATIONS IN CANCER CELLS METABOLIC CHARACTERISTICS OF CANCER CELLS Increased GLYCOLYTIC ACTIVITY (Warburg Effect) Increased production of LACTATE Loss of PASTEUR’S EFFECT (Oxygen inhibition of glycolysis) INCREASED CONSUMPTION Cox4- of GLUTAMINE 2 INCREASED PROTEIN SYNTHESIS DECREASED PROTEOLYSIS DECREASED SYNTHESIS OF FATTY ACIDS (increased lipolysis from host adipose tissue) ENERGETIC METABOLISM IN TUMOURS • WARBURG EFFECT • In the 1920s, Otto Warburg observed that tumor cells consume a large amount of glucose, much • more than normal cells, and convert most of it to lactic acid. This phenomenon, now known as the • ‘Warburg effect,’ is the foundation of one of the earliest general concepts of cancer: that a • fundamental disturbance of cellular metabolic activity is at the root of tumor formation and growth. Biography Otto Heinrich Warburg: • Born-October 8, 1883 in Germany • Died-August 1, 1970 in Berlin, Germany • Son of physicist Emil Warburg • Otto was a German physiologist and medical doctor. • He won a Nobel prize in Physiology and Medicine for his Warburg effect in 1931. • He was one of the twentieth century's leading biochemist One of his Lectures… • "Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar… " -- Dr. Otto H. Warburg in Lecture The Warburg hypothesis The prime cause of cancer is the replacement of the respiration of oxygen…by a fermentation of sugar…” Injury of respiration Aerobic glycolysis De-differentiation Normal cell Phase I Phase II Phase III Cancer cell The Warburg Effect • Pyruvate is an end-product of glycolysis, and is oxidized within the mitochondria.
    [Show full text]
  • Biological Chemistry I: Endings to Glycolysis
    Chemistry 5.07SC Biological Chemistry Fall Semester, 2013 I Lecture 15/16 Endings to Glycolysis: how to regenerate NAD+ and reversible conversion of P to alanine. I. There are three endings to glycolysis. We will look at each transformation and the energetic consequences. 1. Homolactate fermentation which occurs in muscle under anaerobic conditions. 2. Ethanol production which occurs in yeast under anaerobic conditions and is central to the beer and wine industry. 3. AcetylCoA production in aerobic metabolism and a segway into the TCA cycle. 4. We will also discuss conversion of pyruvate to alanine using Vitamin B6, pyridoxal phosphate. PLP is central to all amino acid metabolism and reversible conversion of α- ketoacids and amino acids is central to feeding intermediates into/ and removal of intermediates from the TCA cycle. 1. Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate (P) to lactate (L) using NADH as the cofactor: This ending of the glycolysis pathway is utilized when the demand for ATP is high and the O2 supply is low. Anaerobic glycolysis can continue at high rates for 1 to 3 min. Generation of ATP by this mechanism is much faster than the O/P pathway. In muscles, lactic acid is the end product produced and is transported through the blood to the liver, where it can be converted back to pyruvate and used to make glucose. Lactic acid requires a transporter in muscles and is coupled to H+ transport. Contrary to general belief, it is not lactic acid buildup that causes muscle fatigue and soreness; this phenotype occurs on too long a time scale.
    [Show full text]
  • Gerty Theresa Cori
    NATIONAL ACADEMY OF SCIENCES G ERTY THERESA C ORI 1896—1957 A Biographical Memoir by J OSEPH LARNER Any opinions expressed in this memoir are those of the author(s) and do not necessarily reflect the views of the National Academy of Sciences. Biographical Memoir COPYRIGHT 1992 NATIONAL ACADEMY OF SCIENCES WASHINGTON D.C. GERTY THERESA CORI August 8, 1896-October 26, 1957 BY JOSEPH LARNER ERTY AND CARL CORI'S most significant contributions Gwere the establishment of the cycle of carbohydrates known as "the Cori Cycle," the isolation of glucose 1-phos- phate, and the discovery of phosphorylase and phospho- glucomutase. These discoveries established the enzymatic pathways of glycogenolysis and glycolysis. In glycogen metabolism, Gerty Cori pioneered in the discovery of the debranching enzyme amylo-l,6-glucosidase and its use in the elucidation of glycogen structure by se- rial enzymatic degradation. This pioneering work led to the elucidation of the enzymatic defects in the glycogen storage diseases. Her studies, therefore, extended funda- mental scientific discoveries into the clinical arena, most particularly in the field of pediatrics, her original area of clinical interest and specialization. Gerty Theresa Radnitz was born on August 8, 1896, in Prague, at that time part of the Austro-Hungarian empire. Otto Radnitz, her father, was director general of a sugar refinery in Bohemia. Her mother's brother was professor of pediatrics at the University of Prague. Gerty studied at home until the age of ten, when she went to a girls' prepa- ratory school, from which she graduated in 1912. In 1914, after passing her final examination (matura) at the Tetschen 111 112 BIOGRAPHICAL MEMOIRS Real Gymnasium, she enrolled as a medical student at the Carl Ferdinand University, the German university of Prague.
    [Show full text]
  • Inhibition of the Oxygen Sensor PHD2 in the Liver Improves Survival in Lactic Acidosis by Activating the Cori Cycle
    Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle Tomohiro Suharaa,b,1, Takako Hishikia,c,d,e,1, Masataka Kasaharaa,f,1, Noriyo Hayakawaa,c,d, Tomoko Oyaizua,b, Tsuyoshi Nakanishia,g, Akiko Kuboa,d, Hiroshi Morisakib, William G. Kaelin Jr.h,i,2, Makoto Suematsua,d,2, and Yoji Andrew Minamishimaa,d,2 aDepartment of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan; bDepartment of Anesthesiology, Keio University School of Medicine, Tokyo 160-8582, Japan; cTranslational Research Center, Keio University School of Medicine, Tokyo 160-8582, Japan; dJapan Science and Technology Agency, Exploratory Research for Advanced Technology, Suematsu Gas Biology Project, Core Research for Evolutional Science and Technology, Tokyo 160-8582, Japan; eJapan Science and Technology Agency, Core Research for Evolutional Science and Technology, Tokyo 160-8582, Japan; fDepartment of Pharmacology, Tokyo Dental College, Tokyo 101-0061, Japan; gMS Business Unit, Shimadzu Corporation, Kyoto 604-8511, Japan; hDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02215; and iHoward Hughes Medical Institute, Chevy Chase, MD 20815 Contributed by William G. Kaelin, Jr., August 12, 2015 (sent for review June 22, 2015; reviewed by Ralph J. DeBerardinis) Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible Results and Discussion factor-dependent hypoxic response, including anaerobic glycolysis, Inactivation of Phd2 in the Liver Reduces the Blood Lactate Level. which causes large amounts of lactate to be released from cells into PHD2 is the dominant HIF-prolyl hydroxylase in vivo among all the circulation.
    [Show full text]
  • Development of Inflammatory Hypoxia and Prevalence of Glycolytic Metabolism in Progressing Herpes Stromal Keratitis Lesions
    Development of Inflammatory Hypoxia and Prevalence of Glycolytic Metabolism in Progressing Herpes Stromal Keratitis Lesions This information is current as Pushpa Rao and Susmit Suvas of September 24, 2021. J Immunol 2019; 202:514-526; Prepublished online 7 December 2018; doi: 10.4049/jimmunol.1800422 http://www.jimmunol.org/content/202/2/514 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2018/12/06/jimmunol.180042 Material 2.DCSupplemental References This article cites 56 articles, 15 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/202/2/514.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 24, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Development of Inflammatory Hypoxia and Prevalence of Glycolytic Metabolism in Progressing Herpes Stromal Keratitis Lesions Pushpa Rao* and Susmit Suvas*,† Chronic inflammation in tissues often causes the development of hypoxia.
    [Show full text]
  • Impaired Skeletal Muscle Mitochondrial Pyruvate Uptake
    RESEARCH ARTICLE Impaired skeletal muscle mitochondrial pyruvate uptake rewires glucose metabolism to drive whole-body leanness Arpit Sharma1, Lalita Oonthonpan1†, Ryan D Sheldon1†, Adam J Rauckhorst1, Zhiyong Zhu2, Sean C Tompkins1, Kevin Cho3, Wojciech J Grzesik4,5, Lawrence R Gray1, Diego A Scerbo1, Alvin D Pewa1, Emily M Cushing1, Michael C Dyle2, James E Cox6,7, Chris Adams2,4,8,9,10, Brandon S Davies1,4,9,10, Richard K Shields4,11, Andrew W Norris1,4,5,12, Gary Patti3, Leonid V Zingman2,4,10,13, Eric B Taylor1,4,8,9,10,14* 1Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, United States; 2Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, United States; 3Department of Chemistry, School of Medicine, Washington University, St. Louis, United States; 4Fraternal Order of the Eagles Diabetes Research Center (FOEDRC), Carver College of Medicine, University of Iowa, Iowa City, United States; 5FOEDRC Metabolic Phenotyping Core Facility, Carver College of Medicine, University of Iowa, Iowa City, United States; 6Department of Biochemistry, School of Medicine, University of Utah, Salt Lake City, United States; 7Metabolomics Core Research Facility, School of Medicine, University of Utah, Salt Lake City, United States; 8Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, United States; 9Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, United States; 10Abboud Cardiovascular
    [Show full text]
  • Gluconeogenesis Karoline Hanevik Overview
    Gluconeogenesis Karoline Hanevik Overview Why gluconeogenesis? Substrates/precursors FOUR NEW ENZYMES Regulation of gluconeogensis QUIZ The problem • Glycogen reserves last max. 24 hours • Brain, RBC, eye, kidney medulla +++ require continuous glucose supply • In glycolysis, three enzymes are irreversible Gluconeogenesis is the process that overcomes this! Gluconeogenesis basics • Location: liver (some kidney) • Starts in mitochondria with pyruvate • Finishes in cytoplasm as glucose • Purpose: maintains blood glucose at 24hrs fasting • Liver does NOT use gluconeogenesis as its own energy source • REQUIRES ACETYL-CoA FROM β-OXIDATION OF FATTY ACIDS IN LIVER 1. Pyruvate carboxylase (ABC) 3. Fructose-1,6-bisphosphatase 2. PEP carboxykinase 4. Glucose-6-phosphatase Overview Why gluconeogenesis? Substrates/precursors FOUR NEW ENZYMES Regulation of gluconeogensis QUIZ Substrates for gluconeogenesis 1. Glycerol-3-phosphate (from triacylglycerol in ) 2. Lactate (from anaerobic glycolysis of ) 3. Gluconeogenic amino acids (individual pathways, ) Substrates for gluconeogenesis 1. Glycerol-3-phosphate • Glycerol from hydrolysis of triacylglycerol in fat liver • Glycerol kinase (require ATP) & glycerol phosphate dehydrogenase • Converted to F-1,6-BP via aldolase (reversible enzyme) Substrates for gluconeogenesis 2. Lactate • From anaerobic glycolysis in exercising skeletal muscle and RBCs • THE CORI CYCLE • Pyruvate to lactate resupplies NAD+ for glyceraldehyde-3-P dehydrogenase Substrates for gluconeogenesis 3. Gluconeogenic amino acids All except
    [Show full text]
  • Pathophysiology of Cancer Cachexia: Current Understanding and Areas for Future Research1
    [CANCER RESEARCH (SUPPL.) 42, 721S-726S, February 1982] Pathophysiology of Cancer Cachexia: Current Understanding and Areas for Future Research1 William D. DeWys Nutrition Section, Clinical Investigations Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20205 Abstract use may also be an important variable (32). Food consumption may be considered to be insufficient either in absolute terms or Weight loss and failure to gain weight normally in cancer in terms relative to an increased energy use. Also to be consid patients are attributable to negative energy balance and altered ered when evaluating the relative adequacy of food intake are metabolism. Energy balance is negative because of decreased individual variations in caloric requirements for weight gain (27) intake, increased expenditure, or both. Changes in carbohy and homeostatic adjustment to reduced caloric intake. In nor drate metabolism include glucose uptake and lactate produc mal subjects, a forced reduction in caloric intake leads to a tion by tumor, relative hypoinsulinism, and relative insulin re reduction in caloric expenditure; but in cancer patients, this sistance. Alterations in protein metabolism include preferential normal adaptation may be blunted or blocked (3). uptake of amino acids by the tumor, decreased synthesis of There are relatively few studies of energy balance in cancer some host tissue proteins such as muscle tissue, and increased patients and no detailed studies of energy balance in children synthesis of other host proteins. Lipid metabolism is seemingly with cancer. In adults, a report by Warnold ef al. (32) is less affected. These metabolic changes result in muscle wast probably the best available study.
    [Show full text]
  • Gluconeogenesis Liver
    10/31/17 Gluconeogenesis Liver Kidney Small intestine 1 10/31/2017 Objectives • Give the definition for gluconeogenesis • Know the three irreversible steps in glycolysis that require special enzyme steps to go in the reverse direction • Know the energy requiring steps and how phosphoglycerate kinase works in reverse direction •Understand the role of Fructose-2,6-bisphosphate in gluconeogenesis • Understand the role of acetyl CoA in gluconeogenesis • Know the gluconeogenic steps that require NADH, and the relevance of the NADH shuttles from cytoplasm to mitochondria • Essential role of the vitamins niacin and biotin in gluconeogenesis • Alcohol, Atkins diet and Metformin 2 10/31/2017 • Liver is the primary site of gluconeogenesis (90%); kidney is a minor contributor to gluconeogenesis (10%) • Definition: Synthesis of glucose from amino acids, lactate, glycerol, and propionate • Acetyl-CoA is not a precursor for gluconeogenesis – it is an energy supply and also an activator of pyruvate carboxylase & inhibitor of pyruvate dehydrogenase in mitochondria • Reciprocal regulation of glycolysis and gluconeogenesis maintains blood glucose level • Glycolysis and gluconeogenesis are regulated by hormone-induced enzyme phosphorylations allosteric effectors 3 10/31/2017 Relevance of gluconeogenesis to blood glucose after a normal meal Sources of blood glucose after ingestion of 100 g of glucose 4 10/31/2017 3 irreversible reactions 1 2 Glycolysis vs. 3 Gluconeogenesis 5 10/31/2017 Fructose-2,6-bisphosphate and Gluconeogenesis • F2,6-BP inhibits gluconeogenesis
    [Show full text]
  • Energy Production
    Chapter 3 Energy Production The reason that we eat, besides the fact that food can be so delicious, is for energy and building blocks. Although energy cannot be created or destroyed, its form can change. During metabolism, our bodies break down fuel molecules and trap the energy released within the molecule adenosine triphosphate (ATP). In this chapter, we examine the energy transformations that occur during metabolism. ATP, the Cell’s Energy Currency During exercise, muscles are constantly contracting to power motion, a process that requires energy. The brain is also using energy to maintain ion gradients essential for nerve activity. The source of the chemical energy for these and other life processes is the molecule ATP. ATP contains potential energy that is released during its hydrolysis, or reaction with water. In this reaction, the bond linking the terminal phosphate group (shown below in red) is broken, ATP is converted to ADP (adenosine diphosphate), and 7.3 Cal (kcal) of energy is released. This energy can be used to power the cell’s activities, like muscle contraction. NH NH2 2 NH NH2 N N N N N N N N N H2O O O O N O O N N O O O N N N - O O N O O P O P O P O - - O O P O P O O P O P O P O - O - O - - - H O H O P O P O + O P OH + 7.3 kcal O O O O- O- H O H - - - - - + O O O H H HH - - + O P OOH + OH H O O H H H H H + 7.3 kcal H H OH H ATP H H - OH H ADP OH H InorgaOnic phosphate ATP ADP Inorganic phosphate The energy requirements of an individual vary widely with the activity being performed (Table 1).
    [Show full text]