Visual Anatomy & Physiology First Edition Martini & Ober Chapter 22 (Sections 22.1-22.4) Metabolism & Cellular Respiration Lecture 8 Slides 1-15; 80 min (with review of syllabus and Web sites) [Lecture 1] Slides 16 – 38; 50 min [Lecture 2] 118 min (38 slides plus review of course Web sites and syllabus)

Lecture Overview Enzymes and control of metabolic reactions Energy and metabolic reactions Cellular respiration Overview ATP as the biological energy carrier Oxidation/Reduction Steps in Cellular Respiration Glycolysis The Citric Acid (Krebs) Cycle The Electron Transport Chain Relationship of anabolism to catabolism

Enzymes and Metabolic Reactions Enzymes – Biological catalysts control rates of metabolic reactions lower activation energy needed to start reactions globular proteins with specific shapes not consumed in chemical reactions substrate specific shape of active site determines which substrate(s) the enzyme can act on Figure from: Hole’s Human A&P, 12th edition, 2010

Globular vs. Fibrous Proteins Globular protein – an enzyme attached to its inhibitor Fibrous protein – the structural protein, collagen

Enzymes Lower Activation Energy Enzymes lower the barriers that block chemical reactions, i.e., they lower the activation energy needed to begin energetically favorable reactions

Control of Metabolic Reactions Metabolic pathways series of enzyme-controlled reactions leading to formation of a product each new substrate is the product of the previous reaction Factors that alter activity of enzymes heat radiation substrate concentration required cofactors changes in pH Enzyme names commonly reflect the substrate have the suffix – ase sucrase, lactase, protease, lipase, hydrolase, oxidase

Cofactors and Coenzymes make some enzymes active ions or coenzymes Coenzymes complex organic molecules that act as cofactors (so coenzymes ARE cofactors) vitamins NAD+ Vitamins are essential organic substances that human cells cannot synthesize, i.e., they must come from the diet - required in very small amounts - examples - B vitamins: Thiamine (B1), niacin The protein parts of enzymes that need a nonprotein part (coenzymes, cofactors) to work are called apoenzymes

Overview of Cellular Metabolism Metabolism – All the chemical reactions that occur in an organism KEEP THIS OVERALL SCHEME IN MIND AS WE GO INTO DETAILS!! ETS Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Overview of Glucose Breakdown Figure from: Hole’s Human A&P, 12th edition, 2010

Overview of Cellular Metabolism Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Overview of Catabolism Figure from: Martini, Visual Anatomy & Physiology, Pearson, 2011

A Closer Look at Mitochondria Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001 (Impermeable to charged or polar molecules) Strategically placed in cell where ATP demand is high Outer mitochondrial membrane is very porous – ions and other small mol up to about 5 KDa. Inner membrane imperm to ions/small molecules, but contains transporter proteins (carriers) for nucleotides, fuel molecules. FA oxidation and the TCA cycle occur in the matrix. Concentration of enzymes in the matrix is so high that there is virtually no hydrating water. Enzyme-linked reactions and pathways are so crowded that normal rules of diffusion do not apply!

Carbohydrate Metabolism Most cells generate ATP and other energy-yielding compounds via the catabolism of carbohydrate (and fats) General Reaction sequence in carbohydrate catabolism C6H12O6 + 6 O2  6 CO2 + 6 H2O + ENERGY If the above reaction happened all at once, all the chemical energy contained in the carbohydrate would be DISSIPATED AS HEAT. How does the body harness the energy from carbohydrates?

Harnessing Energy - Stepwise Breakdown of Carbohydrates Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

Energy for Metabolic Reactions ability to do work or change something (potential, kinetic) heat, light, sound, electricity, mechanical energy, chemical energy changed from one form to another, but NEVER destroyed (law of conservation of energy) involved in all metabolic reactions Release of chemical energy most metabolic processes depend on chemical energy oxidation of glucose generates chemical energy cellular respiration releases chemical energy slowly from molecules and makes it available for cellular use

Oxidation and Reduction Revisited gain of O2 loss of e- loss of H (since a H carries an electron with it) increase in oxidation number, e.g., Fe2+ -> Fe3+ Reduction loss of O2 gain of e- gain of H decrease in oxidation number, e.g., Fe3+ -> Fe2+ Oxidation can actually be defined as any of the following: 1) gain of oxygen 2) loss of H 3) loss of electrons 4) increase in oxidation number Reduction can actually be defined as any of the following: 1) loss of oxygen 2) gain of H 3) gain of electrons 4) decrease in oxidation number Oxidation Is Loss of electrons; Reduction Is Gain of electrons “OIL RIG”

Energy of Organic Molecules Carbohydrates like glucose store a great deal of chemical energy (as H·) As carbohydrates (C6H12O6) are oxidized to CO2 they liberate their energy and lose electrons and H (H·) But there must be molecules to accept these electrons, i.e., some molecules must be reduced. In cellular respiration, O2 becomes the final electron (H·) acceptor and is reduced to H2O

Harnessing Energy from Carbohydrates General Reaction sequence in carbohydrate catabolism C6H12O6 + 6 O2  6 CO2 + 6 H2O + ENERGY OXIDATION REDUCTION Electrons (H·) “fall” in energy from organic molecules to oxygen during cellular respiration. That is, e- LOSE potential energy during this process and this energy is captured to make ATP However, electrons CANNOT be transferred directly from glucose to the electron transport chain. There are intermediates – activated carrier molecules

Activated Carrier Molecules Some activated carriers: ATP, NADH, FADH2, GTP, NADPH Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

ATP – An Activated Carrier Molecule Figure from: Hole’s Human A&P, 12th edition, 2010 each ATP molecule has three parts: an adenine molecule a ribose molecule three phosphate molecules in a chain These two components together are called a ? ATP carries its energy in the form or P (phosphate) ATP is a readily interchangeable form of energy for cellular reactions (“common currency”) High-energy bonds

NAD(H) – An Activated Carrier Molecule NAD (and NADP) are specialized to carry high-energy e- and H atoms A “packet” of energy = H· NADH + H+ NAD+ NADH These packets of energy will be passed to oxygen in the electron transport chain, and their energy used to drive the synthesis of ATP Important carriers of e- in catabolism: NADH, FADH2 Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

Overview of Cellular Respiration Anaerobic Cellular respiration (aerobic) Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Overview of Glucose Breakdown Figure from: Hole’s Human A&P, 12th edition, 2010

Overview of Glucose Breakdown Occurs in three major of reaction series… Glycolysis (glucose to pyruvate; in cytoplasm) Citric acid cycle (finishes oxidation begun in glycolysis; in the matrix of mitochondria) Electron transport chain (uses e- transfer to make ATP; on inner membranes of mitochondria) Produces carbon dioxide water ATP (chemical energy) heat (energy has changed form from chemical) Includes anaerobic reactions (without O2) - produce little ATP aerobic reactions (requires O2) - produce most ATP

Glycolysis series of ten reactions breaks down glucose (6C) into 2 molecules of pyruvic acid (pyruvate) (3C) occurs in cytosol anaerobic phase of cellular respiration (that is, it can continue to work with OR without O2) yields 2 ATP and 2 NADH molecules per glucose ADP + Pi ATP Glucose (6C) 2 Pyruvate (3C) NAD+ NADH

Overview of Glycolysis glucose (6C) → 2 pyruvate (3C) Products of glycolysis ATP NADH Pyruvate Figure from: Hole’s Human A&P, 12th edition, 2010 NADH cannot enter the mitochondria directly. Its e- are transported via the glycerol phosphate shuttle (handed to FADH2) or the malate-aspartate shuttle (NADH is regenerated). NADH yields 2.5 ATP, while FADH2 yields 1.5 ATP. NOTE what happens with and without O2 being available…

Metabolism of Pyruvate Without O2 process of forming lactate from glucose is anerobic glycolysis important for regenerating NAD+ so glycolysis can continue to generate ATP for the cell O2 Pyruvic acid (pyruvate) Lactic acid (lactate) NADH + H+ NAD+ NAD+ NADH + H+ Glucose (6C) 2 Pyruvate (3C) ADP + Pi ATP

Overview of Aerobic Reactions Figure from: Hole’s Human A&P, 12th edition, 2010 If oxygen is available – pyruvic acid is used to produce acetyl CoA citric acid (Krebs) cycle begins electron transport chain functions carbon dioxide and water are formed maximum of 36 molecules of ATP produced per glucose molecule

Citric Acid Cycle In mitochondria… What happens… Figure from: Hole’s Human A&P, 12th edition, 2010 In mitochondria… What happens… - Acetyl CoA enters cycle - Citric Acid is converted to various intermediates - Several important products are produced in these interconversions of citric acid… ATP is produced NAD+ is reduced to NADH and FAD is reduced to FADH2 CO2 produced

Source of e- for the Electron Transport Chain Figure from: Hole’s Human A&P, 12th edition, 2010 Notice the flow of electrons to the Electron Transport Chain

Electron Transport Chain NADH and FADH2 carry electrons to the ETC ETC series of electron carriers located in cristae of mitochondria energy from electrons transferred to ATP synthase ATP synthase catalyzes the oxidative phosphorylation of ADP to ATP water is formed *Chemiosmosis Figure from: Hole’s Human A&P, 12th edition, 2010

Oxidative Phosphorylation Chemiosmosis, Chemiosmotic coupling, or Chemiosmotic phosphorylation Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Summary of Cellular Respiration Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Is This All the Metabolism There Is? Definitely NOT! Notice how many lines connect pyruvate and Acetyl CoA to the rest of metabolism

Intermediates of Metabolism Acetyl CoA (2C) and Pyruvate (3C) are important: Allow interconversion of different types of molecules so cell’s needs can be met Figure from: Martini, Visual Anatomy & Physiology, Pearson, 2011

Summary of Catabolism of Proteins, Carbohydrates, and Fats Figure from: Hole’s Human A&P, 12th edition, 2010 Summary of Catabolism of Proteins, Carbohydrates, and Fats Acetyl CoA is a common intermediate in the breakdown of most fuels. Acetyl CoA can be generated by carbohydrates, fats, or amino acids Acetyl CoA can be converted into fatty acids

Pyruvate is a Key Junction in Metabolism Pyruvate is used to synthesize amino acids and Acetyl CoA Pyruvate can also be used to synthesize glucose via gluconeogenesis.  Glycogenesis  Lipo-genesis Glycogenolysis  Lipolysis  * Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Carbohydrate Storage Excess glucose can be stored as glycogen by glycogenesis (liver and muscle cells) stored as fat by lipogenesis converted to amino acids Figure from: Hole’s Human A&P, 12th edition, 2010

Terms to Know… Glycolysis – metabolism of glucose to pyruvate -olysis  breakdown of -neo  new -genesis  creation of Glycolysis – metabolism of glucose to pyruvate Gluconeogenesis – metabolism of pyruvate to glucose (making CHO from non-CHO source) Glycogenesis – metabolism of glucose to glycogen Glycogenolysis – metabolism of glycogen to glucose Lipolysis – breakdown of triglyceride into glycerol and fatty acids Lipogenesis – creation of new triglyceride (fat)

Review Enzymes are biological catalysts Highly specific for their substrate Lower activation energy needed to start a reaction Are not consumed during reaction May require cofactors/coenzymes Effectiveness is greatly affected by temperature, pH, and the presence of required cofactors The goal of metabolism is to provide the cell with energy (catabolism) and materials for the manufacture of cellular components (anabolism)

Review Cells derive energy mainly from carbon compounds like carbohydrates and fats These substances contain a great deal of energy stored in their chemical bonds This energy must be liberated in stepwise fashion Activated carriers serve as intermediates to capture the energy liberated at each step Energy is the ability to do work May be potential or kinetic Changes form Is never destroyed (only converted to another form)

Review Carbohydrates yield energy as they are oxidized to CO2 and O2 is reduced to H2O There are three main steps in extracting energy (in the form of ATP) from carbohydrates Glycolysis Citric Acid (Krebs) Cycle Electron Transport Chain (ETC) Electrons “fall” to lower states of energy in the ETC, giving up energy that is used to synthesize ATP

Review GLYCOLYSIS CONVERSION STEP KREBS CYCLE ELECTRON TRANSPORT CHAIN LOCATION cytoplasm mitochondria Mitochondrial matrix Mitochondrial cristae (inner membrane Oxygen Required? no yes Starting Product glucose (6-C) 2 pyruvates (2 x 3C) Acetyl CoA (2 x 2C) 10 NADH 2 FADH2 End- Products (2 x 3-C) 2 ATP 2 NADH 2 Acetyl CoA 2 CO2 6 NADH 4 CO2 24 ATP 4 ATP TOTAL 32 ATP

Review Anabolism is intimately tied to catabolism Energy derived from catabolism is used to drive anabolic reactions Some molecules are important junctions between catabolism and anabolism Acetyl CoA Generated from pyruvate, fatty acids, and amino acids Can be used to synthesize fatty acids and other molecules CANNOT be used to generate pyruvate Pyruvate Can be synthesized from glucose and amino acids can be used to synthesize amino acids, glucose and acetyl CoA NOTE, however, that in humans fatty acids cannot be converted to glucose