Metabolism

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. 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.

3. 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)

4. Stages of Metabolism

5. 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

6. Carbohydrate Catabolism

7. 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 acid lactic aicd

8. Glycolysis

9. 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 C�s) is split into two 3-carbon compounds: Glyceraldehyde 3-phosphate (GAP)

10. Glycolysis: Phase 3 Phase 3: Oxidation and ATP formation The 3-carbon sugars are oxidized (reducing NAD+); i.e., 2 H�s + NAD NADH2 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

13. 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)

15. 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 Remember, 1 6 C Glucose ? 2-2 carbon acetyl coenzyme A (A-CoA)

16. Krebs Cycle

18. 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 + P ATP

19. 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 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

20. Electron-Transport Chain

21. ATP Synthase The enzyme consists of three parts: a rotor, a knob, and a rod Current created by H+ causes the rotor and rod to rotate This rotation activates catalytic sites in the knob where ADP and Pi are combined to make ATP

23. Anaerobic Respiration Breakdown of glucose in absence of oxygen Produces 2 molecules of lactic acid and 2 molecules of ATP Phases Glycolysis Lactic acid formation

24. Lipid Metabolism Most products of fat metabolism are transported in lymph as chylomicrons Lipids in chylomicrons are hydrolyzed by plasma enzymes and absorbed by cells Only neutral fats are routinely oxidized for energy Catabolism of fats involves two separate pathways Glycerol pathway Fatty acids pathway

25. Lipolysis viab-oxidation

26. Lipid Synthesis

27. Protein Metabolism Non-essential amino acids can be formed by transamination, transfer of an amine group to keto acid. Can also be eaten. If used for energy, amino acids undergo oxidative deamination. Ammonia and keto acids are produced as by-products of oxidative deamination. Ammonia is converted to urea and excreted. Amino acids are not stored in the body

28. Protein Catabolism

29. 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

30. Interconversion of Nutrient Molecules

31. Summary: Carbohydrate Metabolic Reactions

32. Summary: Lipid and Protein Metabolic Reactions