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Anatomy and Physiology I Cellular Metabolism Instructor: Mary Holman Metabolism • Refers to all the chemical reactions in the body that use or release energy • It is the energy-balancing between synthesis reactions and decomposition reactions in the body Anabolism • a synthesis reaction • the joining of smaller molecules to form larger ones • requires energy • dehydration synthesis - removal of water Formation of a disaccharide: a molecule of H20 is removed Fig. 4.1a CH2OH CH2OH O H HO O H H OH H H OH H OH HO OH H H OH H20 Monosaccharide (glucose) + H H Monosaccharide (glucose) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. OH Fig. 4.1b An example of Anabolism: A Disaccharide is formed by dehydration synthesis CH2OH CH 2OH O H HO O H H H O OH H H OH Disaccharide (maltose) H H + OH H H OH H2O OH + Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Water Fig. 4.2a Dehydration Synthesis of a Fat H H C O OH HO C (CH2)14 CH3 O H C OH HO C (CH2)14 CH3 O H C OH HO C (CH2)14 CH3 H Glycerol + 3 fatty acid molecules Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 4.2b H H C O O C (CH2)14 CH3 O H C O C H2O + (CH2)14 CH3 H2O H2O O H C O C (CH2)14 CH3 H Fat molecule (triglyceride) + 3 water molecules Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 4.3a Another example of Anabolism: Two amino acids joined to make a dipeptide H H N H C O C N O R Amino acid H H H H + C O C R Amino acid Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H Dipeptide Fig. 4.3b Peptide bond H N H H O C C R R N H C O C + OH H O 2 H Dipeptide molecule Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. + Water Catabolism • a decomposition reaction • the breaking down of larger molecules to form smaller ones • releases energy • often requires H2O Fig. 4.2 Anabolism - dehydration synthesis - requires energy H H C O OH HO C H (CH2)14 CH3 H C O O O H C OH HO C C OH HO C (CH2)14 CH3 H C O C + (CH2)14 CH3 (CH2)14 CH3 H C O C H2O H2O H2O O H Glycerol (CH2)14 CH3 O O H C (CH2)14 CH3 H + 3 fatty acid molecules Fat molecule (triglyceride) Catabolism - hydrolysis - produces energy Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. + 3 water molecules Enzymes • Molecules that speed up chemical reactions • Are not used up in the reaction so they can be recycled • Usually are proteins • Names often end in -ase Action of Enzymes Fig. 4.4 Substrate molecules Product molecule Active site (a) Enzyme molecule (b) Enzyme-substrate complex Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (c) Unaltered enzyme molecule Fig. 4.5 Substrate 1 Enzyme A Enzyme Specificity Substrate 2 Enzyme B Substrate 3 Enzyme C Substrate 4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Enzyme D Product Negative feedback mechanism Fig. 4.6 Inhibition Rate-limiting Enzyme A Substrate Substrate 2 1 Enzyme B Substrate 3 Enzyme C Substrate 4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Enzyme D Product Fig. 4.7 ATP - Adenosine triphosphate Adenosine Adenine Ribose Phosphates P P Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. P ADP to ATP Fig. 4.8a Energy transferred from cellular respiration used to reattach phosphate P P P P ATP P ADP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. P Fig. 4.8b Potential energy is stored in the bonds between the outer 2 P groups of ATP Hi energy bonds P P P ATP ADP P P P Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Energy is transferred and utilized by metabolic reactions when phosphate bond is broken Cellular Respiration or Cellular Metabolism • The breakdown in the body of high-energy molecules to produce energy • Catabolism of glucose C6H12O6 produces ATP • Three steps: – Glycolysis – Citric Acid Cycle – Electron transport chain Glycolysis Fig. 4.9a • 1 molecule of glucose (6 carbon) • results in 2 molecules of pyruvic acid (3 carbon) • happens in the cytosol • anaerobic Glucose Glycolysis High-energy electrons (e–) The 6-carbon sugar glucose is broken down in the cytosol into two 3-carbon pyruvic acid molecules with a net gain of 2 ATP and the release of high-energy electrons. 2 Glycolysis Cytosol 1 Pyruvic acid Pyruvic acid 2 ATP used and 4 ATP generated = Net 2 ATP 2 electron pairs released to NAD+ Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ATP NAD+ and FAD Deliver High Energy Hydrogen To the Electron Transport System NAD+ + 2H NADH + H+ When NAD+ accepts 2 hydrogen atoms, the two electrons and a hydrogen nucleus bind to NAD+ to form NADH. The remaining H ion (a hydrogen nucleus or H+ ) is released FAD + 2H FADH2 Events After Glycolysis If O2 Adequate Pyruvic acid enters the mitochondrion and is modified to enter the citric acid cycle If O2 not Adequate Pyruvic acid is converted into lactic acid until there is adequate oxygen for the aerobic steps of cellular respiration Fig. 4.9b Preparation for Citric Acid Cycle • If O2 is adequate, pyruvic acid enters mitochondrion • releases a carbon as CO2 • combines with coenzyme A to form acetyl coenzyme A Pyruvic acid 2 Citric Acid Cycle The 3-carbon pyruvic acids generated by glycolysis enter the mitochondria. Each loses a carbon (generating CO2) and is combined with a coenzyme to form a 2-carbon acetyl coenzyme A (acetyl CoA). More high-energy electrons are released. Pyruvic acid High-energy electrons (e–) CO2 Acetyl Co A One electron pair passed to NAD+ for each molecule of pyruvic acid converted to Acetyl CoA Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 4.9c Citric Acid Cycle or Krebs Cycle • Acetyl coenzyme A combines with oxaloacetic acid to form citric acid • CO2 formed as carbons are removed • cycle regenerates oxaloacetic acid • happens aerobically Acetyl Co A Each acetyl Co A combines with a 4-carbon oxaloacetic acid to form the 6-carbon citric acid, for which the cycle is named. For each citric acid, a series of reactions removes 2 carbons (generating 2 CO2’s), synthesizes 1 ATP, and releases more high-energy electrons. The figure shows 2 ATP, resulting directly from 2 turns of the cycle per glucose molecule that enters glycolysis. Mitochondrion 3 Citric acid Oxaloacetic acid Citric acid cycle High-energy electrons (e–) 2 CO2 2 ATP For each turn of the citric acid cycle: 3 electron pairs passed to NAD+ 1 electron pair passed to FAD 1 ATP generated Fig 4.9 Glucose 2 pr Glycolysis The 6-carbon sugar glucose is broken down in the cytosol into two 3-carbon pyruvic acid molecules with a net gain of 2 ATP and release of high-energy electrons. Fig. 4.9 Pyruvic acid Citric Acid Cycle 2 2 Glycolysis ATP Cytosol 1 High-energy electrons (e–) Pyruvic acid 2 pr The 3-carbon pyruvic acids generated by glycolysis enter the mitochondria. Each loses a carbon (generating CO2 and is combined with a coenzyme to form a 2-carbon acetyl coenzyme A (acetyl CoA). More high-energy electrons are released. High-energy electrons (e–) CO2 Acetyl CoA 3 Each acetyl CoA combines with a 4-carbon oxaloacetic 8 pr total Citric acid cycle 3 pr to Nad+/turn 1 pr to Fad+/turn High-energy electrons (e–) 2 CO2 1 ATP/turn 2 Electron Transport Chain 4 The high-energy electrons still contain most of the chemical energy of the original glucose molecule. Special carrier molecules bring the high-energy electrons to a series of enzymes that convert much of the remaining energy to more ATP molecules. The other products are heat and water. The function of oxygen as the final electron acceptor in this last step is why the overall process is called aerobic respiration. Citric acid Oxaloacetic acid Mitochondrion acid to form the 6-carbon citric acid, for which the cycle is named. For each citric acid, a series of reactions removes 2 carbons (generating 2 CO2’s), synthesizes 1 ATP, and releases more high-energy electrons. The figure shows 2 ATP, resulting directly from 2 turns of the cycle per glucose molecule that enters glycolysis. ATP Electron transport chain 32–34 2e– and 2H+ 1 2 O2 H2 O ATP Fig. 4.11 Pyruvic acid from glycolysis Cytosol Carbon atom P NAD+ Phosphate MitochondrionCoA Coenzyme A CO2 NADH + H+ Acetic acid CoA Acetyl CoA Citric Acid Cycle (replenish molecule) Oxaloacetic acid Citric acid (finish molecule) (start molecule) CoA NADH + H+ NAD+ Malic acid Isocitric acid NAD+ Citric acid cycle CO2 NADH + H+ Fumaric acid a -Ketoglutaric acid CO2 CoA NAD+ FADH2 FAD Succinyl-CoA Succinic acid CoA ADP + P ATP NADH + H+ Electron Transport Chain Fig. 4.12 • Each NADH carried e- pair creates 3 ATP • Each FADH2 carried e- pair creates 2 ATP • Oxygen serves as final e- acceptor and produces H20 ADP + P ATP synthase ATP Energy NADH + H+ Energy 2H+ NAD+ + 2e– Energy FADH2 2H+ + 2e– FAD Electron transport chain 2e2H+ O2 10 e- pairs carried by NADH = 30 ATP* 2 e- pairs carried by FAD = 4 ATP Glycolysis = 2 ATP Citric Acid Cycle = 2 ATP H2O Net ATP from 1 molecule Glucose = 38 ATP* Cellular Respiration Overview From: Principles of A&P Tortora & Grabowsky Fig. 4.13 Glucose High energy electrons (e–) and hydrogen ions (H+) 2 Pyruvic acid ATP Pyruvic acid Cytosol Mitochondrion High energy electrons (e–) and hydrogen ions (h+) CO2 Acetyl CoA Oxaloacetic acid Citric acid High energy electrons (e–) and hydrogen ions (H+) 2 CO2 2 ATP Electron transport chain 32-34 1/2 O2 ATP 2e– + 2H+ H 2O Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 4.15 Food Food 1 Pg. 134 Fig. 4.15 Proteins (egg white) Carbohydrates (toast, hashbrowns) Amino acids Fats (butter) Simple sugars (glucose) Glycerol Breakdown of large macromolecules to simple molecules 1 Fatty acids 2 Glycolysis ATP 2 Pyruvic acid Acetyl coenzyme A Citric acid cycle 3 CO2 ATP High energy electrons carried by NADH and FADH2 Electron transport chain ATP 2e– and 2H+ –NH2 CO2 ½ O2 H2 O Waste products © Royalty Free/CORBIS. 2 Breakdown of simple molecules to acetyl coenzyme A accompanied by production of limited ATP and high energy electrons 3 Complete oxidation of acetyl coenzymeA to H2O and CO2 Produces high energy electrons(carried by NADH and FADH2), which yield much ATP via the electron transport chain