Modulo A_Parte II_Introducao ao metabolismo celular PDF

Energy and Metabolism Metabolism is the sum of Catabolism and Anabolism...

Energy and Metabolism Metabolism is the sum of Catabolism and Anabolism Opposite chemical processes. Catabolism releases energy (exergonic), and Anabolism takes up energy (endergonic) Breakdown - Proteins to Amino Acids, Starch to Glucose Synthesis - Amino Acids to Proteins, Glucose to Starch  Common intermediate Two phases of metabolism Catabolism Anabolism Degradative Biosynthetic Oxidative Reductive Energy Liberated Energy Required Converging Diverging building blocks -- generally hydrolytic Breakdown of macromolecules to Energy currency The basic reactions for formation of each are: Oxidized substances lose energy ADP + Pi → ATP Reduced substances gain energy AMP + Pi → ADP Coenzymes act as hydrogen (or electron) acceptors NAD+ + H+ → NADH Two important coenzymes are nicotinamide adenine FADH + H+ → FADH2 dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) Oxidation of glucose is shown by the overall reaction: C6H12O6 + 6O2 à 6H2O + 6CO2 + 36 ATP + heat DG = -686kcal/mol of glucose  Glycolysis First stage of glucose catabolism. No oxygen needed. All organisms uses this process. It occurs in the cytoplasm where the necessary enzymes are located. 6C Glucose is converted into two 3C pyruvate. Small amount of energy, 2ATP, is produced. Pathway of glycolysis is strictly regulated according to the cell’s needs for energy. The rate limiting step of the pathway is reaction 3, the phosphorylation of F 6-P, which is catalyzed by phospho-fructokinase. Glycolysis A three-phase pathway in which: – Glucose is oxidized into pyruvic acid (PA) – NAD+ is reduced to NADH + H+ – ATP is synthesized by substrate-level phosphorylation Pyruvic acid: end-product of glycolysis – Moves on to the Krebs cycle in an aerobic pathway (i.e. sufficient oxygen available to cell) – Is reduced to lactic acid in an anaerobic environment (insufficient O2 available to cell) pyruvic acid lactic acid Glycolysis: Phase 1, 2 and 3 Phase 1: Sugar activation – Two ATP molecules activate glucose into fructose-1,6-diphosphate The 1 and 6 indicate which carbon atom to which they are attached. Phase 2: Sugar cleavage (splitting) – Fructose-1,6-bisphosphate (6 C’s) is split into two 3-carbon compounds: Glyceraldehyde 3-phosphate (GAP) Phase 3: Oxidation and ATP formation – The 3-carbon sugars are oxidized (reducing NAD+) – The terminal phosphates are cleaved and captured by ADP to form four ATP molecules Ciclo de Cori  Fate of pyruvic acid Krebs Cycle: Preparatory Step Pyruvic acid from glycolysis is converted to acetyl coenzyme A (A-CoA) in three main steps: – Decarboxylation 1 carbon is removed from pyruvic acid; 3C ® 2C molecule The lost carbon forms carbon dioxide; exhaled – Oxidation 2 Hydrogen atoms are removed from pyruvic acid (‘oxidation’) and picked up by NAD NAD+ is reduced to NADH + H+ – Formation of acetyl CoA – the resulting acetic acid is combined with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA (ACoA) Krebs Cycle An eight-step cycle in which each acetic acid is decarboxylated and oxidized, generating: Three molecules of NADH + H+ (ox/red) One molecule of FADH2 (ox/red) Two molecules of CO2 (decarboxylation) One molecule of ATP (substrate level phosphorylation For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle  Mechanism of Oxidative Phosphorylation 4 2 4 The hydrogens delivered to the chain are split into protons (H+) and electrons – The protons are pumped across the inner mitochondrial membrane to the intermembrane space – This creates a pH and concentration gradient (of H+) – The electrons are shuttled from one acceptor to the next Electrons are delivered to oxygen, forming oxygen ions Oxygen ions attract H+ that were pumped into the intermembrane space to form water H+ that were pumped to the intermembrane space: – Diffuse down their gradients back to the matrix via ATP synthase (from greater to lesser concentration) – Release energy to make ATP Summary of cellular respiration Copyright 2009, John Wiley & Sons, Inc.  Lipid and protein catabolism Other Metabolic Pathways Lipolysis via b-oxidation  Beta-oxidation of fatty acids β-oxidation of FA produces acetyl CoA and NADH and FADH2, which are sources of energy (ATP) First, FA are converted to acyl CoA in the cytoplasm: Carnitine shuttle For transport into mitochondria, CoA is replaced with carnitine by acylcarnitine transferase I Inside mitochondria a corresponding enzyme (II) forms acyl CoA Malonyl CoA inhibits acylcarnitine transferase I So, when FA synthesis is active, FA are not transported into mitochondria Defects in FA transport (including carnitine deficiency) are known b-oxidação dos ácidos gordos – uma via em espiral Cycles of b-Oxidation The length of a fatty acid: Determines the number of oxidations and The total number of acetyl CoA groups Carbons in Acetyl CoA b-Oxidation Cycles Fatty Acid (C/2) (C/2 –1) 12 6 5 14 7 6 16 8 7 18 9 8 b-Oxidation and ATP Activation of a fatty acid requires: 2 ATP One cycle of oxidation of a fatty acid produces: 1 NADH 3 ATP 1 FADH2 2 ATP Acetyl CoA entering the citric acid cycle produces: 1 Acetyl CoA 12 ATP  ATP for Lauric Acid C12 ATP production for lauric acid (12 carbons): Activation of lauric acid -2 ATP 6 Acetyl CoA 6 acetyl CoA x 12 ATP/acetyl CoA 72 ATP 5 Oxidation cycles 5 NADH x 3ATP/NADH 15 ATP 5 FADH2 x 2ATP/FADH2 10 ATP Total 95 ATP  Protein Catabolism The liver is the major site of protein degradation in mammals Proteins are degraded into amino acids Ammonium ion is converted to urea in most mammals First step in protein degradation is the removal of the nitrogen  Protein Catabolism Catabolism of proteins: -amino acids undergo deamination to remove the amino group -remainder of the amino acid is converted to a molecule that enters glycolysis or the Krebs cycle -for example: (alanine is converted to pyruvate; aspartate is converted to oxaloacetate) Amino acid Catabolism