Metabolism i

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  • 1. Metabolism Total of all chemical changes that occur in body. Includes: Anabolism: energy-requiring process where small molecules joined to form larger molecules E.g. Glucose + Glucose Catabolism: energy-releasing process where large molecules broken down to smaller Energy in carbohydrates, lipids, proteins is used to produce ATP through oxidation-reduction reactions

2. Catabolism and Anabolism BreakdownProteins to Amino Acids, Starch to GlucoseSynthesisAmino Acids to Proteins, Glucose to Starch Metabolism is the sum of Catabolism and Anabolism Opposite chemical processes. Catabolism releases energy (exergonic), and Anabolism takes up energy (endergonic)We can consider these bioenergetics in terms of the physical laws of thermodynamics 3. Energy and Metabolism 4. Metabolic Pathways4 5. Interconversion of Nutrient Molecules Glycogenesis Excess glucose used to form glycogen Lipogenesis When glycogen stores filled, glucose and amino acids used to synthesize lipids Glycogenolysis Breakdown of glycogen to glucose Gluconeogenesis Formation of glucose from amino acids and glycerol 6. Common intermediateAs vias catablicas convergem para uns poucos produtos finais As vias anablicas divergem para a sntese de muitas biomolculas 7. Breakdown of macromolecules to building blocks -- generally hydrolytic 8. Metabolic Pathways The enzymatic reactions of metabolism form a network of interconnected chemical reactions, or pathways. The molecules of the pathway are called intermediates because the products of one reaction become the substrates of the next. Enzymes control the flow of energy through a pathway. Intermediary Metabolism 9. A metabolic pathway has many steps That begin with a specific molecule and end with a product That are each catalyzed by a specific enzyme Enzyme 1 AEnzyme 3 DCB Reaction 1Starting moleculeEnzyme 2Reaction 2Reaction 3 Product 10. Oxidation-Reduction Reactions Oxidation occurs via the loss of hydrogen or the gain of oxygen Whenever one substance is oxidized, another substance is reduced Oxidized substances lose energy Reduced substances gain energy Coenzymes act as hydrogen (or electron) acceptors Two important coenzymes are nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) 11. Comparao dos estados de oxidao dos tomos de carbono nas biomolculas (quanto mais oxidado mais estvel a molcula, logo menos energia pode ser extrada da quebra das ligaes) 12. FotossnteseRespirao 13. Four general stages in the biochemical energy production process in the human body. 14. ATP Adenosine Triphosphate ATP powers most energy requiring process in living systems. Components Energy stored in the triphosphate group Cells use ATPs to drive endergonic reactions ATP ADP (releases energy) Cells are continually producing new ATPs ADP ATP (requires energy)ATP - the energy currency of cells 15. The interconversion of ATP and ADP is the principal medium for energy exchange in biological processes. 16. Flavin Adenine Dinucleotide, FAD (a) and Nicotinamide Adenine Dinucleotide, NAD (b) 17. Carbohydrate Metabolism Since all carbohydrates are transformed into glucose, it is essentially glucose metabolism Oxidation of glucose is shown by the overall reaction: C6H12O6 + 6O2 6H2O + 6CO2 + 36 ATP + heat Glucose is catabolized in three pathways Glycolysis Krebs cycle The electron transport chain and oxidative phosphorylation G = -686kcal/mol of glucose 18. Carbohydrate Catabolismtransferring a phosphate directly to ADP from another moleculeuse of ATP synthase and energy derived from a proton (H+) gradient to make ATP 19. Glycolysis A three-phase pathway in which: Glucose is oxidized into pyruvic acid (PA) It loses 2 pairs of hydrogens NAD+ is reduced to NADH + H+ It accepts 2 pairs of hydrogens lost by glucose 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 acidlactic acid 20. Glycolysis 21. Energy investement phase 22. Glycolysis: Phase 1 and 2 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 Cs) is split into two 3-carbon compounds: Glyceraldehyde 3-phosphate (GAP) 23. Glycolysis: Phase 3 Phase 3: Oxidation and ATP formation The 3-carbon sugars are oxidized (reducing NADH2 NAD+); i.e., 2 Hs + NAD Inorganic phosphate groups (Pi) are attached to each oxidized fragment The terminal phosphates are cleaved and captured by ADP to form four ATP molecules The final products are: Two pyruvic acid molecules Two NADH + H+ molecules (reduced NAD+) A net gain of two ATP molecules 24. ATP Production and Glycolysis 25. 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 cells 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. 26. Anaerobic Metabolism Fermentation in animal cellsLactic Acid Fermentation Breakdown of glucose in absence of oxygen Produces 2 molecules of lactic acid and 2 molecules of ATP Phases Glycolysis Lactic acid formation 27. Anaerobic Metabolism Fermentation in plants, yeastAgainonly 2 ATP per glucose 28. Aerobic MetabolismGlycolysis = 2 ATP Krebs Cycle and ETC = 34 ATPIf enough O2 is presentTo Krebs Cycle and ETC~ 36 more ATP per glucose! 29. Glycolysis For glycolysis to continue, NADH must be recycled to NAD+ by either: 1. aerobic respiration occurs when oxygen is available as the final electron acceptor 2. fermentation occurs when oxygen is not available; an organic molecule is the final electron acceptor 30. Ciclo de Cori 31. Gluconeognese Sintese de "glucose nova" a partir de metabolitos comuns Os seres humanos consumem 160 g de glucose por dia 75% dessa consumida no crebro Os fluidos corporais contm apenas 20 g de glucose As reservas de glicognio rendem 180-200 g de glucose Portanto o corpo deve ser capaz de sintetizar a sua prpria glucose 32. Gluconeognese Ocorre principalmente no figado e nos rins.No uma mera reverso da gliclise por duas razes:O balano energtico tem que mudar de modo a tornar a gluconeogenese favorvel ( G da glicolise = -74 kJ/mol) A regulao de uma das vias deve ser activada e a da via reversa deve ser inibida isto requer algo de novo ! Sete dos passos da gliclise esto conservados e trs passos so substituidos: Passos 1, 3, e 10 (que so os passos regulados!)As reaces novas devem seguir um novo caminho de reaco espontneo (G negativo na direco da sintese de aucar), e devem ser regulados de maneira diferente. 33. Regulao da Gluconeogenese Controlo reciproco com a gliclise Quando a glicolise est em funcionamento, a gluconeogenese no est a realizar-se Quando o estado energtico da clula elevado, a glicolise deve ser desligada e o piruvato (entre outros), deve ser utilizado para a sintese e armazenamento de glucose Quando o estado energtico da clula baixo, a glucose deve ser rpidamente degradada de modo a fornecer energia Os passos regulados da gliclise so os mesmos passos que so regulados na direco oposta ! 34. Krebs Cycle: Preparatory Step Occurs in the mitochondrial matrix and is fueled by pyruvic acid and fatty acids 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+ (see next slide) Formation of acetyl CoA the resulting acetic acid is combined with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA (ACoA) 35. Each transition of pyruvate to acetyl coenzyme A yields one NADH and one CO2.The acetyl coenzyme A then enters the Krebs cycle. 36. Citric Acid Cycle Melvin Calvin (UCB) 37. 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 38. Krebs Cycle 39. Krebs Cycle After glycolysis, pyruvate oxidation, and the Krebs cycle, glucose has been oxidized to: - 6 CO2 - 4 ATP - 10 NADH - 2 FADH2 40. Oxidative PhosphorylationComplex IIIComplex IVComplex IComplex V 41. Electron carriers take these high energy electrons to the Electron Transport Chain Electrons are run down an electron slide The energy released from this slide is used to make ATP The electrons and H+ are accepted by oxygen and become water 42. Electron Transport Chain Food (glucose) is oxidized and the released hydrogens: Are transported by coenzymes NADH and FADH2 Enter a chain of proteins bound to metal atoms (cofactors) Combine with molecular oxygen to form water Release energy The energy released is harnessed to attach inorganic phosphate groups (Pi) to ADP, making ATP by oxidative phosphorylation phosphorylation - to add phosphate to a substance ADP + PATP 43. Mechanism of Oxidative Phosphorylation The hydrogens delivered to the chain are split into protons (H+) and electrons The protons are pumped across the inner mitochondrial membrane