Cellular Metabolism Chapter 4 Copyright  The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Cellular Respiration Occurs in a series of reactions: Glycolysis Citric acid cycle (Kreb’s Cycle) Electron transport chain (ETC)

Cellular Respiration Produces: Carbon dioxide Water ATP (chemical energy) Heat Includes: Anaerobic reactions (without O2) - produce little ATP Aerobic reactions (requires O2) - produce most ATP

Glycolysis Sugar splitting Series of ten reactions Breaks down glucose into 2 pyruvic acid molecules Occurs in cytosol (cytoplasm) Anaerobic phase of cellular respiration Yields two ATP molecules per glucose molecule Summarized by three main phases or events: Phosphorylation Splitting Production of NADH and ATP

Glycolysis Event 1 – Phosphorylation Two phosphates added to glucose Requires ATP Phase 1 priming Phase 2 cleavage Phase 3 oxidation and formation of ATP and release of high energy electrons 2 ADP 2 NADH + H+ 2 NAD+ P ATP Glyceraldehyde phosphate Glucose Dihydroxyacetone 2 4 ADP 4 Fructose-1,6-diphosphate O2 2 Pyruvic acid 2 Lactic acid To citric acid cycle and electron transport chain (aerobic pathway) Carbon atom Phosphate Event 2 – Splitting (cleavage) 6-carbon glucose split into two 3-carbon molecules

Glycolysis Event 3 – Production of NADH (nicotinamide adenine dinucleotide hydride or coenzyme 1) and ATP Hydrogen atoms are released Hydrogen atoms bind to NAD+ to produce NADH NADH delivers hydrogen and high energy electrons to electron transport chain if oxygen is available ADP (adenosine diphosphate) is phosphorylated to become ATP Two molecules of pyruvic acid are produced Two molecules of ATP are generated Phase 1 priming Phase 2 cleavage Phase 3 oxidation and formation of ATP and release of high energy electrons 2 ADP 2 NADH + H+ 2 NAD+ P ATP Glyceraldehyde phosphate Glucose Dihydroxyacetone 2 4 ADP 4 Fructose-1,6-diphosphate O2 2 Pyruvic acid 2 Lactic acid To citric acid cycle and electron transport chain (aerobic pathway) Carbon atom Phosphate

Anaerobic Reactions If oxygen is not available (Fermentation): Electron transport system cannot accept new electrons from NADH Pyruvic acid is converted to lactic acid or ethanol (for yeast and bacteria) Glycolysis is inhibited ATP production is less than in aerobic reactions Phase 1 priming Phase 2 cleavage Phase 3 oxidation and formation of ATP and release of high energy electrons 2 ADP 2 NADH + H+ 2 NAD+ P ATP Glyceraldehyde phosphate Glucose Dihydroxyacetone 2 4 ADP 4 Fructose-1,6-diphosphate O2 2 Pyruvic acid 2 Lactic acid To citric acid cycle and electron transport chain (aerobic pathway) Carbon atom Phosphate

Aerobic Reactions If oxygen is available: Pyruvic acid is used to produce acetyl CoA Citric acid cycle begins Electron transport chain functions Carbon dioxide and water are formed Up to 38 molecules of ATP are produced per each glucose molecule ATP 2 Glucose Pyruvic acid Acetyl CoA CO2 2 CO Citric acid O H 2e – + 2H + Electron transport chain 32-34 Cytosol Mitochondrion High energy electrons (e–) and hydrogen ions (H+) hydrogen ions (h+) Oxaloacetic acid High energy electrons (e–) and hydrogen ions (H+)

Citric Acid Cycle Begins when acetyl CoA combines with oxaloacetic acid to produce citric acid Citric acid is changed into oxaloacetic acid through a series of reactions Cycle repeats as long as pyruvic acid and oxygen are available 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 Fumaric acid Malic acid Cytosol Mitochondrion NADH + H + NAD CoA P Carbon atom Phosphate Coenzyme A -Ketoglutaric acid For each citric acid molecule: One ATP is produced Eight hydrogen atoms are transferred to NAD+ and FAD (Flavin adenine dinucleotide) Two CO2 produced

Electron Transport Chain NADH and FADH2 carry hydrogen and high energy electrons to the ETC ETC is a series of enzyme complexes located in the inner membrane of the mitochondrion (the matrix) Energy from electrons transferred to ATP synthase ATP synthase catalyzes the phosphorylation of ADP to ATP Water is formed (Oxygen is the final electron “carrier”) ATP ADP + ATP synthase Electron transport chain Energy P 2H+ + 2e– 2e– NADH + H+ NAD+ FADH2 FAD O 2 H2O

Summary of Cellular Respiration (page 81) Glycolysis Cytosol Mitochondrion A T P 2 Glucose High-energy electrons (e–) 2e – and 2H + H O 32–34 CO Pyruvic acid 2 CO Acetyl Co Citric acid Oxaloacetic acid 1 3 4 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 CO2 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 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. 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. Electron transport chain cycle

Carbohydrate Storage Carbohydrate molecules from foods can enter: Catabolic pathways for energy production Anabolic pathways for storage

Carbohydrate Storage Excess glucose stored as: Glycogen (primarily by liver and muscle cells) Fat Converted to amino acids Hydrolysis Monosaccharides Energy + CO2 + H2O Glycogen or Fat Amino acids Carbohydrates from foods Catabolic pathways Anabolic

Summary of Catabolism of Proteins, Carbohydrates, and Fats (page 83) High energy electrons carried by NADH and FADH2 Breakdown of simple molecules to acetyl coenzyme A accompanied by production of limited ATP and high energy electrons H2O 2e– and 2H+ Waste products –NH2 CO2 Citric acid cycle Electron transport chain Amino acids Acetyl coenzyme A Simple sugars (glucose) Glycerol Fatty acids Proteins (egg white) Carbohydrates (toast, hashbrowns) Food Fats (butter) Pyruvic acid ATP Breakdown of large macromolecules to simple molecules Glycolysis 1 2 3 © Royalty Free/CORBIS. ½ O2 Complete oxidation of acetyl coenzyme A to H2O and CO2 produces high energy electrons (carried by NADH and FADH2), which yield much ATP via the electron transport chain