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

Fig. 4.1a CH 2 OH H H OH O H Monosaccharide (glucose) + H HO H OH H H O H Monosaccharide (glucose) H HO H OH CH 2 OH Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Formation of a disaccharide: a molecule of H 2 0 is removed H20H20

Fig. 4.1b H H OH O H Disaccharide (maltose) H2OH2O Water + H HO HH H OH O H H O H CH 2 OH Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. An example of Anabolism: A Disaccharide is formed by dehydration synthesis +

Fig. 4.2a HC H Glycerol3 fatty acid molecules + OHHO HCOHHO HC C C COHHO OH O O Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (CH 2 ) 14 CH 3 Dehydration Synthesis of a Fat

Fig. 4.2b C C C O O O HC H Fat molecule (triglyceride)3 water molecules + HC HCO O O H H2OH2O Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H2OH2O H2OH2O (CH 2 ) 14 CH 3 +

Fig. 4.3a Amino acid + N H H CC H R H O N H H CC H R H O Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. O Another example of Anabolism: Two amino acids joined to make a dipeptide

Fig. 4.3b N H H C R Dipeptide molecule + Peptide bond H N H OH H O N H2OH2O Water Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. O CC C R + Dipeptide

Catabolism a decomposition reaction the breaking down of larger molecules to form smaller ones releases energy often requires H 2 O

Fig. 4.2 H C H Glycerol3 fatty acid molecules + OHHO H COHHO H C C C COHHO OH O O C C C O O O HC H Fat molecule (triglyceride)3 water molecules + HC HCO O O H H2OH2O (CH 2 ) 14 CH 3 H2OH2O H2OH2O Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (CH 2 ) 14 CH 3 Anabolism - dehydration synthesis - requires energy Catabolism - hydrolysis - produces energy +

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

Fig. 4.4 Unaltered enzyme molecule Enzyme-substrate complex Active site (a) (b)(c) Enzyme molecule Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Product molecule Substrate molecules Action of Enzymes

Fig. 4.5 Substrate 1 Enzyme A Substrate 2 Enzyme B Substrate 3 Enzyme C Substrate 4 Enzyme D Product Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Enzyme Specificity

Fig. 4.6 Inhibition Substrate 1 Substrate 2 Enzyme B Substrate 3 Enzyme C Substrate 4 Enzyme D Product Rate-limiting Enzyme A Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Negative feedback mechanism

Fig. 4.7 Ribose Adenosine PPP Adenine Phosphates Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ATP - Adenosine triphosphate

Fig. 4.8a Energy transferred from cellular respiration used to reattach phosphate PP PPP P ADP ATP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ADP to ATP

Fig. 4.8b ADP ATP Energy is transferred and utilized by metabolic reactions when phosphate bond is broken PP PPP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. P Potential energy is stored in the bonds between the outer 2 P groups of ATP Hi energy bonds

Cellular Respiration or Cellular Metabolism The breakdown in the body of high-energy molecules to produce energy Catabolism of glucose C 6 H 12 O 6 produces ATP Three steps: – Glycolysis – Citric Acid Cycle – Electron transport chain

Fig. 4.9a 1 Glycolysis Cytosol ATP 2 Glucose High-energy electrons (e – ) Pyruvic acid 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycolysis 2 ATP used and 4 ATP generated = Net 2 ATP 2 electron pairs released to NAD + 1 molecule of glucose (6 carbon) results in 2 molecules of pyruvic acid (3 carbon) happens in the cytosol anaerobic

NAD + + 2H NADH + H + NAD + and FAD Deliver High Energy Hydrogen To the Electron Transport System 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 FADH 2

Events After Glycolysis If O 2 Adequate If O 2 not Adequate Pyruvic acid is converted into lactic acid until there is adequate oxygen for the aerobic steps of cellular respiration Pyruvic acid enters the mitochondrion and is modified to enter the citric acid cycle

Fig. 4.9b 2 High-energy electrons (e – ) CO 2 Pyruvic acid Acetyl Co A The 3-carbon pyruvic acids generated by glycolysis enter the mitochondria. Each loses a carbon (generating CO 2 ) and is combined with a coenzyme to form a 2-carbon acetyl coenzyme A (acetyl CoA). More high-energy electrons are released. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Citric Acid Cycle Preparation for Citric Acid Cycle If O 2 is adequate, pyruvic acid enters mitochondrion releases a carbon as CO 2 combines with coenzyme A to form acetyl coenzyme A One electron pair passed to NAD + for each molecule of pyruvic acid converted to Acetyl CoA

Fig. 4.9c 3 Mitochondrion High-energy electrons (e – ) ATP2 Acetyl Co A Citric acid cycle Oxaloacetic acid 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 CO 2 ’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. 2 CO 2 Citric Acid Cycle or Krebs Cycle Acetyl coenzyme A combines with oxaloacetic acid to form citric acid CO 2 formed as carbons are removed cycle regenerates oxaloacetic acid happens aerobically For each turn of the citric acid cycle: 3 electron pairs passed to NAD+ 1 electron pair passed to FAD 1 ATP generated

Fig Glycolysis Cytosol Mitochondrion ATP 2 Glucose High-energy electrons (e – ) 2e – and 2H + 2 H2OH2OO2O2 Electron transport chain ATP 32–34 Pyruvic acid 2 CO 2 Acetyl CoA Citric acid cycle Oxaloacetic acid High-energy electrons (e – ) ATP 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. Citric Acid Cycle The 3-carbon pyruvic acids generated by glycolysis enter the mitochondria. Each loses a carbon (generating CO 2 and is combined with a coenzyme to form a 2-carbon acetyl coenzyme A (acetyl CoA). More high-energy electrons are released. Each acetyl CoA 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 CO 2 ’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. Electron Transport Chain 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. 1 2 CO 2 2 pr 3 pr to Nad+/turn 1 pr to Fad+/turn 1 ATP/turn 8 pr total Fig 4.9

Fig Citric acid cycle ADP + ATP Pyruvic acid from glycolysis Citric acid (start molecule) Acetyl CoA (replenish molecule) Acetic acid Oxaloacetic acid (finish molecule) Isocitric acid CO 2 Succinyl-CoA Succinic acid FAD FADH 2 Fumaric acid Malic acid Cytosol Mitochondrion NADH + H + NAD + NADH + H + NAD + NADH + H + NAD + CoA P NADH + H + NAD + P CoA Coenzyme A Carbon atom Phosphate -Ketoglutaric acid a CO 2 Citric Acid Cycle

Fig ATP ADP + ATP synthase Electron transport chain Energy P 2H + + 2e – 2e - 2H + NADH + H + NAD + FADH 2 FAD O2O2 H2OH2O Energy 2H + + 2e – Electron Transport Chain Each NADH carried e - pair creates 3 ATP Each FADH2 carried e- pair creates 2 ATP Oxygen serves as final e - acceptor and produces H e- pairs carried by NADH = 30 ATP* 2e- pairs carried by FAD = 4 ATP Glycolysis = 2 ATP Citric Acid Cycle = 2 ATP Net ATP from 1 molecule Glucose = 38 ATP*

From: Principles of A&P Tortora & Grabowsky Cellular Respiration Overview

Fig Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ATP 2 2 Glucose Pyruvic acid Acetyl CoA CO 2 2 CO 2 Citric acid Oxaloacetic acid H2OH2O 2e – + 2H + High energy electrons (e – ) and hydrogen ions (H + ) High energy electrons (e – ) and hydrogen ions (H + ) Electron transport chain ATP Cytosol Mitochondrion High energy electrons (e – ) and hydrogen ions (h + ) 1/2 O 2

Fig High energy electrons carried by NADH and FADH 2 H2OH2O 2e – and 2H + Waste products –NH 2 CO 2 Citric acid cycle Electron transport chain Amino acids Acetyl coenzyme A Simple sugars (glucose) GlycerolFatty acids Proteins (egg white) Carbohydrates (toast, hashbrowns) Food Fats (butter) Pyruvic acid ATP Glycolysis ATP © Royalty Free/CORBIS. ½ O 2 Fig High energy electrons carried by NADH and FADH 2 Complete oxidation of acetyl coenzymeA to H 2 O and CO 2 Produces high energy electrons(carried by NADH and FADH 2 ), which yield much ATP via the electron transport chain Breakdown of simple molecules to acetyl coenzyme A accompanied by production of limited ATP and high energy electrons H2OH2O 2e – and 2H + Waste products –NH 2 CO 2 Citric acid cycle Electron transport chain Amino acids Acetyl coenzyme A Simple sugars (glucose) GlycerolFatty acids Proteins (egg white) Carbohydrates (toast, hashbrowns) Food Fats (butter) Pyruvic acid ATP Breakdown of large macromolecules to simple molecules Glycolysis ATP © Royalty Free/CORBIS. ½ O Pg. 134