Medical Biochemistry II MD140 Metabolism Overview PDF

Medical Biochemistry II MD140 Metabolism Overview Dr. Stephanos Christodoulides [email protected]  OBJECTIVES Define the terms: metabolism, catabolism, anabolism; Draw a diagrammatic scheme that relates the main energy conserving metabolic pathways (gl...

Medical Biochemistry II MD140 Metabolism Overview Dr. Stephanos Christodoulides [email protected]  OBJECTIVES Define the terms: metabolism, catabolism, anabolism; Draw a diagrammatic scheme that relates the main energy conserving metabolic pathways (glycolysis, TCA cycle, β-oxidation, oxidative phosphorylation) to each other; Indicate the subcellular locations of each of the pathways; Indicate the central role played by cofactors such as ATP, UTP, and GTP;  Overview of Metabolism Catabolism The metabolic breakdown of complex substances into smaller products – -including the breakdown of carbon compounds with the liberation of energy for use by the cell or organism Source: Essential Cell Biology. Alberts, Bray, Johnson, Hopkin, Lewis, Raff, Roberts & Walter Copyright 2004 © Garland Science Publishing  Overview of Metabolism Anabolism The energy requiring part of metabolism in which simpler substances are transformed into more complex ones -as in growth or other biosynthetic processes Source: Essential Cell Biology. Alberts, Bray, Johnson, Hopkin, Lewis, Raff, Roberts & Walter Copyright 2004 © Garland Science Publishing  Definition: Metabolism Series of enzyme reactions within cells for converting fuel molecules into ‘useful energy’ The enzyme reactions of synthesis/ breakdown/interconversion of essential biomolecules  Metabolism Catabolism Anabolism names end in ‘lysis’ names end in ‘genesis’ glycolysis gluconeogenesis lipolysis lipogenesis glycogenolysis glycogenesis generate ATP & NADH Use ATP, GTP, UTP (mitochondrial) mostly in cytosol  Integration Pathways of glycolysis and Tricarboxylic Acid (TCA) cycle act together to convert glucose to CO 2 C 6 H 12 O 6 + 6O 2 6CO 2 + 6H 2 O + 30 ATP (oxidative phosphorylation) and through mitochondrial respiration provide energy for tissues, such as muscle, kidney and brain  Summary Diagrams Biochemistry textbooks show summary diagrams of metabolic pathways with links to other main metabolic processes. Cell Biology textbooks show summary diagrams with the cellular location of the main metabolic pathways.  Catabolism of sugars, fats & amino acids occurs in 3 stages Glucose Fatty Acids Amino Acids glycolysis β-oxidation transamination 1 pyruvate CH3 – C -- ‘Acetate’ 2C unit = O Krebs cycle or 2 NADH, FADH2 2H TCA cycle CO2 CO2 2H + O H2O 3 Oxidative phosphorylation ADP + Pi ATP Cell Structure Cytosol Mitochondrion  Importance of ATP most of the metabolic pathways are catabolic pathways that result in ATP synthesis ATP as the ‘energy currency’ of the cell Adenosine triphosphate Chemically stable at pH 6-9 Structural features recognised by specific proteins, enzymes etc. Metabolic A B C D E Enzyme 1 enzyme 2 enzyme 3 enzyme 4  Enzymatic reactions The rate of a biochemical reaction is dependent on enzyme activity. The direction (equilibrium) of a reaction is dependent on the properties of the chemical molecules themselves. Endergonic/exergonic reactions  ΕΞΩΘΕΡΜΕΣ vs. ΕΝΔΟΘΕΡΜΕΣ Exergonic Vs. Endergonic reactions Reversible & Irreversible Steps in a Metabolic Pathway  The rate of an enzyme reaction can be regulated in several ways: 1. by altering the availability of the substrate, (e.g. by increasing the transport system into the cell) 2. by increasing the amount of enzyme present in the cell, by increasing the rate of transcription from the gene in DNA into mRNA) ‘up regulation’ or ‘induction’ ‘down regulation’ or ‘repression’  Regulation Mechanisms for Enzymes already present in the Cell 3. Interconversion of ‘active’ & ‘inactive’ forms of key enzymes Interconversion of Active & Inactive Forms of the Enzyme by Covalent Modification ATP (Covalent modifications include the addition or removal of chemical groups) REGULATION OF GLYCOGEN PHOSPHORYLASE P Metabolic reactions require: organic cofactors firmly attached Examples of Enzyme Cofactors ATP acts as a ‘high energy’ cofactor for kinase enzymes give a phosphate group ATP breakdown releases approx. 31 kJ of energy per mole  General role of ATP ATP acts as ‘high energy’ cofactor in the cell for driving mechanical events such as pumps, transporters, contractile events & movement Other ‘high energy’ nucleotides other ‘high energy’ nucleotide cofactors are used to drive specific biosynthetic reactions UTP drives the synthesis of complex sugars GTP drives the synthesis of proteins GTP as ‘high energy’ cofactor 10 Check Points for Metabolic Pathways 1 Definition 2 Sub cellular location 3 Which tissues? 4 Function(s) 5 Summary diagram 6 Cofactors 7 Reversibility 8 Control mechanisms 9 Links with other pathways 10 Clinical importance  Questions? [email protected]