E-Book, Englisch, 112 Seiten
ISBN: 978-0-12-802011-1
Verlag: Elsevier Reference Monographs
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Illustrates disease involvement in metabolic mapsContains coverage of cutting-edge technology, including iPS, HPLC and HPLC-MS, and FACS methodProvides in-depth technical detail as well as conceptual frameworks of biochemistry and experimental design in the context of the human organismIncludes a biotechnology study, featuring application of basic biochemistry principles
1969 Graduated Kitasato University School of Medicine
1979 Promoted Assistant Professor of Saitama Medical University
1982 Promoted Assosiate Professor of Saitama Medical Universiy
1983 Co-opereted the intestinal alkaline phosphatase with Professor David H. Alpers, Washington University School of Medicine (St. Louis)
1988 Received a Kodama Memorial Award from Japanese Society of Electrophoresis.
1996 Became Chief Professor of Biochemistry, Saitama Medical University.
2010 Resigned from Saitama Medical University.
2010- Promoted a Visiting Professor of Toho University School of Medicine
Expert Field: alkaline phosphatase, amylase, oxizized HDL
Autoren/Hrsg.
Weitere Infos & Material
Chapter 4 Metabolic Pathways in the Human Body
Abstract
Major metabolic pathways for several biological materials are described, including carbohydrate and energy metabolism by electron transfer systems, lipids, lipoproteins, amino acids, nucleic acid and protein biosynthesis. Metabolic syndrome is caused by disruption of metabolic pathways or their regulation. Disorders in anaerobic sugar metabolism and glycogen metabolism can cause diabetes mellitus. Alzheimer and Parkinson disease are examples of disorders of electron transfer systems. Concerning the nature of sugar chains, certain blood group substances are useful as tumor markers. Dysfunction of the glycosylphosphatidylinositol moiety binding to asparagine-linked sugar chains causes paroxysmal nocturnal hemoglobinuria. Lipid metabolism is an important indicator of lipoprotein and fatty acids; both cholesterol and lipid metabolism have relevance to disease. Disorders of amino acid metabolism and nucleic acid metabolism and the resulting diseases are illustrated. An overview of protein synthesis is provided. Keywords
amino acid blood group electron transfer system glycoprotein lipid lipoprotein metabolic pathway nucleic acid protein synthesis; sugar Contents Sugar Metabolism 26 Glycolysis 26 Preparatory Stage 26 Payoff Phase 29 Location of Glycolysis 31 Role of Glycolysis 31 Metabolism of the Tricarboxylic Acid Cycle and Electron Transfer System 33 Regulation of Glucose in the Bloodstream 33 Glycogen Metabolism 36 Glycogen Synthesis 36 Glycogen Degradation 36 Use of Glucose-6-Phosphoric Acid 36 Glyconeogenesis 38 Pentose Phosphate Pathway 39 Blood Groups 39 Glycoprotein Synthesis 41 Lipid Metabolism 43 Steroid Hormones 46 Lipoprotein Metabolism 49 Lipoprotein Species 49 Amino Acid Metabolism 52 Branched-Chain Amino Acid Metabolism 55 Leucine 55 Isoleucine and Valine 55 Phenylalanine and Tyrosine 58 Urea Cycle 59 Nucleic Acid Metabolism 59 Purine Metabolism 59 Nucleotide Decomposition 59 Gout 59 Partial Deficiency of PRPP Enzymes Without Adenosine Deaminase 60 Protein Biosynthesis 60 Start 61 Extension 61 Stop 62 References 63 Sugar Metabolism
The mechanism of absorption of sugar in the small intestine is shown in Figure 4.1. Figure 4.1 Mechanism of absorption of sugar in the small intestine.
Glucose is absorbed by type 1 glucose transporter (GLUT1), which is located in microvilli in the proximal enterocytes. Then, elevated glucose in the enterocytes can be taken into the bloodstream by type 2 glucose transporter (GLUT2). SGLT1: type 1 sodium-dependent glucose transporter; NCC: Na+/Cl- cotransporter. Glycolysis
Preparatory Stage The five steps in the first half of glycolysis are called the preparatory or energy investment phase. In the preparatory phase, two molecules of adenosine triphosphate (ATP) are supplied, and the phosphorylation of glucose and conversion to glyceraldehyde-3-phosphate (G3P) take place. Stage 1: Phosphorylation of Glucose Glucose is phosphorylated with the enzyme hexokinase in the first step of the preparatory phase. ATP is a donor of a phosphate group; the carbon 6 (C6) position of glucose transfers to a ?-phosphate residue, and glucose-6-phosphate (G6P) is generated. This reaction requires magnesium ions (Mg2+). Hexokinase has several forms (isozymes). Although the catalyst advances the same reaction, the isozymes are coded by different genes. Mammals have four isozymes of hexakinase. These isozymes have different affinities (Michaelis constant or Km value) for glucose. The Km value of hexokinase I, II and III is 10-6 M. The Km of hexokinase IV (also called glucokinase) is usually 10-2 M, depending on the role of glucokinase. A large concentration of glucokinase exists in hepatic cells. Since the glucose concentration in blood is lower than the Km, glucokinase does not usually act fully against glucose. In this case, other isozymes of hexokinase catalyze the reaction. However, when the glucose concentration increases, glucokinase will begin to act. Since glucokinase is hardly saturated, even if the glucose concentration in hepatic cells increases markedly, glucose can move rapidly to the glycolytic pathway or glycogen synthesis shunt. The intracellular glucose concentration is always low, and extracellular glucose inhibits the flow of glucose to the outside of the cell and promotes membrane transport into the cell. Insulin can promote the action of hexokinase. In contrast, glucagon can repress the action of hexokinase, resulting in the acceleration of glucose-6-phosphatase activity. Then, the gluconeogenesis reaction will be promoted in vivo. Stage 2: Isomerization of Glucose-6-Phosphate Glucose-6-phosphate (G6P) is changed into fructose-6-phosphate (F6P) by phosphoglucoisomerase (phosphoglucose isomerase) in the second step. This reaction also requires Mg2+. F6P can enter the glycolytic pathway from the next point. This reaction has a low free energy charge. It can progress in both directions, but since F6P is rapidly consumed in the following step, it is unlikely to undergo the reverse reaction. The a-anomer of G6P, a-D-glucopyranose-6-phosphate, combines with the enzyme preferentially, the ring opens and it converts an aldose to a ketose. This isomerization reaction is important for the glycolytic pathway after this step. Stage 3: Phosphorylation of Fructose-6-Phosphate In the third step, phosphofructokinase-1 (PFK-1) transfers the phosphate residue of ATP to the C1 hydroxyl residue of F6P, generating fructose-1,6-bisphosphate (F1,6BP). This reaction requires Mg2+ and fructose-2,6-bisphosphate. After ingestion of a meal, fructose-2,6-bisphosphate is elevated, resulting in the above-mentioned reaction advancing a speedy glycolysis reaction. Before a meal, the concentration of fructose-2,6- bisphosphate is decreased, resulting in upregulation of F1,6BP and facilitation of gluconeogenesis. Although G6P and F6P are also metabolized in pathways other than the glycolytic system, F1,6BP is metabolized only by the glycolytic pathway. The reaction in which PFK-1 acts as a catalyst is irreversible, and PFK-1 does not use the reverse reaction in the case of glyconeogenesis. Therefore, two enzyme reactions modulated by fructose- 2,6-bisphosphate are a key point of the glycolytic and/or glyconeogenesis system. Stage 4: Cleavage The first three reactions of glycolysis are the preparative stages for cleaving F1,6BP and making two triose phosphates. In this step, F1,6BP is cleaved by F1,6BP aldolase (or just aldolase) into G3P and dihydroxyacetone phosphate (DHAP). This reaction, catalyzed by aldolase, results in a positive large standard free energy change in the direction in which F1,6BP is cleaved, within the cells. The reaction is mostly in equilibrium and is not a control point of glycolysis. When the intracellular metabolite concentration is low, the free energy change is low and a reverse reaction occurs easily. There are two types of aldolase: type I aldolase exists in animals and plants, and type II aldolase in fungi and bacteria. The two types differ in the cleavage mechanism of hexose. Stage 5: Isomerization of Triose Phosphate Of the two molecules described in the preceding paragraph, only G3P serves as a substrate continuing in the next steps of the reaction. However, DHAP is promptly changed into G3P by a reversible reaction of triose phosphate isomerase. Since triose phosphate isomerase acts as the catalyst of a reaction on a solid unique target, only the D-isomer is generated. The carbon 1 (C1) position of the G3P is derived from the C3 of DHAP, and the C2 and C3 positions of the G3P originate from the C2 and C1 positions of glucose. Of the C1, C2 and C3 positions of the glyceraldehyde-3-phosphate generated in step 4, the above C3 is the C4, C5 and C6 positions of glucose. However, the distinction does not separate chemically the carbon of each position of the two G3Ps. Two molecules of G3P are generated by this reaction from a hexose molecule, and the preparatory phase of glycolysis ends. Payoff Phase The five steps in the second half of glycolysis are called the payoff phase or energy phase. In the payoff phase, two molecules of G3P are changed into pyruvate, four molecules of adenosine diphosphate (ADP) per molecule of glucose are changed into four ATP, and a part of the free energy of glucose is saved. Since two molecules of ATP were consumed in the preparatory phase, the net gain of ATP through glycolysis will be two molecules. Moreover, two molecules of nicotinamide adenine dinucleotide (NADH) per molecule of glucose are...
