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Chapter 4 Lecture PowerPoint Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Faulkner State Community College Bio 201 Anatomy and Physiology I Chapter 4 J D Nall Adjunct 2 Hole’s Human Anatomy and Physiology Twelfth Edition Shier w Butler w Lewis Chapter 4 Cellular Metabolism Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 3 4.1: Introduction • Metabolic processes – all chemical reactions that occur in the body There are two (2) types of metabolic reactions: • Anabolism • Larger molecules are made from smaller ones • Requires energy • Catabolism • Larger molecules are broken down into smaller ones • Releases energy 4 4.2: Metabolic Processes • Consists of two processes: • Anabolism • Catabolism 5 Anabolism • Anabolism provides the materials needed for cellular growth and repair • Dehydration synthesis • Type of anabolic process • Used to make polysaccharides, triglycerides, and proteins • Produces water Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. CH2OH CH2OH O H O H H CH2OH H O H H CH2OH H O H H H H H H2O HO OH H H OH HO OH Monosaccharide + OH H H OH Monosaccharide OH HO OH H H OH O Disaccharide OH H H OH OH + Water 6 Anabolism Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H H H O C OH HO C (CH2)14 CH3 H O C O O H C OH HO C C OH HO C (CH2)14 CH3 O (CH2)14 CH3 H C O O H C C H2O H2O H2O (CH2)14 CH3 O (CH2)14 CH3 H H C O C (CH2)14 CH3 H + Glycerol 3 fatty acid molecules + Fat molecule (triglyceride) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 3 water molecules Peptide bond H H N H C C R Amino acid H H O N O H H + C H O C R Amino acid N O H H H O C C R R N C H H Dipeptide molecule O C OH H2O + Water 7 Catabolism • Catabolism breaks down larger molecules into smaller ones • Hydrolysis • A catabolic process • Used to decompose carbohydrates, lipids, and proteins • Water is used to split the substances • Reverse of dehydration synthesis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. CH2OH CH2OH O H O H H CH2OH H O H H CH2OH H O H H H H H H2O HO OH H H OH HO OH Monosaccharide + OH H H OH Monosaccharide OH HO OH H H OH O Disaccharide OH H H OH + OH 8 Water Catabolism Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H H H O C OH HO C (CH2)14 CH3 H O C O O H C OH HO C C OH HO C (CH2)14 CH3 O (CH2)14 CH3 H C O O H C C H2O H2O H2O (CH2)14 CH3 O (CH2)14 CH3 H H C O C (CH2)14 CH3 H + Glycerol 3 fatty acid molecules + Fat molecule (triglyceride) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 3 water molecules Peptide bond H H N H C C R Amino acid H H O N O H H + C H O C R Amino acid N O H H H O C C R R N C H H Dipeptide molecule O C OH H2O + Water 9 4.3: Control of Metabolic Reactions • Enzymes • Control rates of metabolic reactions • Lower activation energy needed to start reactions • Most are globular proteins with specific shapes • Not consumed in chemical reactions • Substrate specific • Shape of active site determines substrate Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Substrate molecules Product molecule Active site Enzyme molecule (a) Enzyme-substrate complex (b) (c) Unaltered enzyme molecule 10 Animation: How Enzymes Work Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 11 Enzyme Action • Metabolic pathways • Series of enzyme-controlled reactions leading to formation of a product • Each new substrate is the product of the previous reaction Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Substrate 1 Enzyme A Substrate 2 Enzyme B Substrate 3 Enzyme C Substrate 4 Enzyme D • Enzyme names commonly: • Reflect the substrate • Have the suffix – ase • Examples: sucrase, lactase, protease, lipase Product 12 Cofactors and Coenzymes • Cofactors • Make some enzymes active • Non-protein component • Ions or coenzymes • Coenzymes • Organic molecules that act as cofactors • Vitamins 13 Factors That Alter Enzymes • Factors that alter enzymes: • Heat • Radiation • Electricity • Chemicals • Changes in pH 14 Regulation of Metabolic Pathways • Limited number of regulatory enzymes • Negative feedback Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Inhibition Rate-limiting Enzyme A Substrate Substrate 2 1 Enzyme B Substrate 3 Enzyme C Substrate 4 Enzyme D Product 15 4.4: Energy for Metabolic Reactions • Energy is the capacity to change something; it is the ability to do work • Common forms of energy: • Heat • Light • Sound • Electrical energy • Mechanical energy • Chemical energy 16 ATP Molecules • Each ATP molecule has three parts: • An adenine molecule • A ribose molecule • Three phosphate molecules in a chain Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. P P Energy transferred and utilized by metabolic reactions when phosphate bond is broken Energy transferred from cellular respiration used to reattach phosphate P P P P P 17 Release of Chemical Energy • Chemical bonds are broken to release energy • We burn glucose in a process called oxidation 18 4.5: Cellular Respiration • Occurs in a series of reactions: 1. Glycolysis 2. Citric acid cycle (aka TCA or Kreb’s Cycle) 3. Electron transport system 19 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 20 Glycolysis • Series of ten reactions • Breaks down glucose into 2 pyruvic acid molecules • Occurs in cytosol • Anaerobic phase of cellular respiration • Yields two ATP molecules per glucose molecule Summarized by three main phases or events: 1. Phosphorylation 2. Splitting 3. Production of NADH and ATP 21 Glycolysis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Event 1 - Phosphorylation • Two phosphates added to glucose • Requires ATP Event 2 – Splitting (cleavage) • 6-carbon glucose split into two 3-carbon molecules Glucose Phase 1 priming Carbon atom P Phosphate 2 ATP 2 ADP Fructose-1,6-diphosphate P P Phase 2 cleavage Dihydroxyacetone phosphate P Phase 3 oxidation and formation of ATP and release of high energy electrons Glyceraldehyde phosphate P P 2 NAD+ 4 ADP 2 NADH + H+ 4 ATP 2 Pyruvic acid O2 O2 2 NADH + H+ 2 NAD+ 2 Lactic acid To citric acid cycle and electron transport chain (aerobic pathway) 22 Glycolysis Event 3 – Production of NADH and ATP • Hydrogen atoms are released • Hydrogen atoms bind to NAD+ to produce NADH • NADH delivers hydrogen atoms to electron transport system if oxygen is available • ADP is phosphorylated to become ATP • Two molecules of pyruvic acid are produced • Two molecules of ATP are generated Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glucose Phase 1 priming Carbon atom P Phosphate 2 ATP 2 ADP Fructose-1,6-diphosphate P P Phase 2 cleavage Dihydroxyacetone phosphate P Phase 3 oxidation and formation of ATP and release of high energy electrons Glyceraldehyde phosphate P P 2 NAD+ 4 ADP 2 NADH + H+ 4 ATP 2 Pyruvic acid O2 O2 2 NADH + H+ 2 NAD+ 2 Lactic acid To citric acid cycle and electron transport chain (aerobic pathway) 23 Anaerobic Reactions Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • If oxygen is not available: • Electron transport system cannot accept new electrons from NADH • Pyruvic acid is converted to lactic acid • Glycolysis is inhibited • ATP production is less than in aerobic reactions Glucose Phase 1 priming Carbon atom P Phosphate 2 ATP 2 ADP Fructose-1,6-diphosphate P P Phase 2 cleavage Dihydroxyacetone phosphate P Phase 3 oxidation and formation of ATP and release of high energy electrons Glyceraldehyde phosphate P P 2 NAD+ 4 ADP 2 NADH + H+ 4 ATP 2 Pyruvic acid O2 O2 2 NADH + H+ 2 NAD+ 2 Lactic acid To citric acid cycle and electron transport chain (aerobic pathway) 24 Aerobic Reactions Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • If oxygen is available: • Pyruvic acid is used to produce acetyl CoA • Citric acid cycle begins • Electron transport system functions • Carbon dioxide and water are formed • 34 molecules of ATP are produced per each glucose molecule Glucose High energy electrons (e–) and hydrogen ions (H+) 2 ATP Pyruvic acid 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 ATP O2 – + 2e + 2H H2O 25 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 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pyruvic acid from glycolysis Cytosol CO2 Carbon atom P NAD+ Phosphate Mitochondrion CoA Coenzyme A NADH + H+ Acetic acid CoA Acetyl CoA (replenish molecule) Oxaloacetic acid Citric acid (finish molecule) (start molecule) CoA NADH + H+ NAD+ Malic acid Isocitric acid NAD+ • For each citric acid molecule: • One ATP is produced • Eight hydrogen atoms are transferred to NAD+ and FAD • Two CO2 produced Citric acid cycle CO2 Fumaric acid NADH + H+ -Ketoglutaric acid CO2 CoA NAD+ FADH2 NADH + H+ FAD Succinic acid CoA Succinyl-CoA ADP + P ATP 26 Electron Transport System • NADH and FADH2 carry electrons to the ETS • ETS is a series of electron carriers located in cristae of mitochondria • Energy from electrons transferred to ATP synthase • ATP synthase catalyzes the phosphorylation of ADP to ATP • Water is formed Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ADP + P ATP synthase ATP Energy NADH + H+ Energy 2H+ + 2e– NAD+ Energy FADH2 2H+ + 2e– FAD Electron transport chain 2e– 2H+ O2 27 H2O Summary of Cellular Respiration Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glucose Glycolysis High-energy electrons (e–) 2 ATP Glycolysis Cytosol 1 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. Pyruvic acid Pyruvic acid Citric Acid Cycle 2 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 Citric acid Oxaloacetic acid Mitochondrion 3 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. Citric acid cycle High-energy electrons (e–) 2 CO2 2 ATP 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. Electron transport chain 32–34 ATP 2e– and 2H+ O2 H2O 28 Carbohydrate Storage • Carbohydrate molecules from foods can enter: • Catabolic pathways for energy production • Anabolic pathways for storage 29 Carbohydrate Storage • Excess glucose stored as: • Glycogen (primarily by liver and muscle cells) • Fat • Converted to amino acids Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Carbohydrates from foods Hydrolysis Monosaccharides Catabolic pathways Anabolic pathways Energy + CO2 + H2O Glycogen or Fat Amino acids 30 Summary of Catabolism of Proteins, Carbohydrates, and Fats Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Food Proteins (egg white) Carbohydrates Carbohydrates (toast, (toast,hashbrowns) hashbrowns) Amino acids Fats (butter) Simple sugars (glucose) Glycolysis Glycerol Fatty acids ATP 2 Breakdown Breakdownofofsimple simple molecules moleculestotoacetyl acetyl coenzyme coenzymeAA accompanied accompaniedby by production productionofoflimited limited ATP ATPand andhigh highenergy energy electrons electrons Pyruvic acid Acetyl coenzyme coenzyme A A Acetyl Citric acid cycle 3 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 CO2 ATP ATP High High energy energy electrons electrons carried carried by NADH by NADH and and FADH FADH22 Electron Electron transport transport chain chain 1 Breakdown Breakdown ofoflarge large macromolecules macromolecules totosimple simplemolecules molecules ATP 2e– and 2H+ –NH2 CO2 ½ O2 H2O Waste products © Royalty Free/CORBIS. 31 4.6: Nucleic Acids and Protein Synthesis • Instruction of cells to synthesize proteins comes from a nucleic acid, DNA 32 Genetic Information • Genetic information – instructs cells how to construct proteins; stored in DNA • Gene – segment of DNA that codes for one protein • Genome – complete set of genes • Genetic Code – method used to translate a sequence of nucleotides of DNA into a sequence of amino acids 33 4.1 From Science to Technology DNA Profiling Frees A Prisoner 34 Structure of DNA Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (a) Hydrogen bonds P C G Thymine (T) Adenine (A) Cytosine (C) Guanine (G) P P T P P C G P P G P C P A P • Two polynucleotide chains • Hydrogen bonds hold nitrogenous bases together • Bases pair specifically (A-T and C-G) • Forms a helix • DNA wrapped about histones forms chromosomes G C A Nucleotide strand G C T C Segment of DNA molecule G A (b) Globular histone proteins Metaphase chromosome (c) Chromatin 35 Animation: DNA Structure Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 36 DNA Replication Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. A • Hydrogen bonds break between bases • Double strands unwind and pull apart • New nucleotides pair with exposed bases • Controlled by DNA polymerase T C G G C C G T A Original DNA molecule C G C G A T A C T G A T G C C Region of replication G T T A T A A A A T G C T G A C C T T A T G G G A Newly formed DNA molecules C G A 37 Animation: DNA Replication Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 38 4.2 From Science to Technology Nucleic Acid Amplification 39 Genetic Code • Specification of the correct sequence of amino acids in a polypeptide chain • Each amino acid is represented by a triplet code 40 RNA Molecules • Messenger RNA (mRNA): • Making of mRNA (copying of DNA) is transcription • Transfer RNA (tRNA): • Carries amino acids to mRNA • Carries anticodon to mRNA • Translates a codon of mRNA into an amino acid • Ribosomal RNA (rRNA): • Provides structure and enzyme activity for ribosomes 41 RNA Molecules • Messenger RNA (mRNA): • Delivers genetic information Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. from nucleus to the cytoplasm DNA • Single polynucleotide chain P • Formed beside a strand of DNA P S A U T A G C P S Direction of “reading” code • RNA nucleotides are complementary to DNA nucleotides (exception – no thymine in RNA; replaced with uracil) RNA S P S S P P S S P C G G C P S S P P S 42 Animation: Stages of Transcription Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 43 Animation: How Translation Works Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 44 Protein Synthesis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. DNA double helix Cytoplasm Nucleus T A G C A T T A G C A T GC A T C G T A CG T A G C A T GC A T C G T A CG T A G C A T GC A T C G T A CG T A 3 Translation begins as tRNA anticodons recognize complementary mRNA codons, thus bringing the correct amino acids into position on the growing polypeptide chain 6 2 mRNA leaves the nucleus and attaches Messenger to a ribosome RNA A T U A G C G G C G G C C C G T U A C C G C C G G C G C G C A A T A A T C C G G C G G G C C G C A T A G G C G G C C G C U A T C C G C C G A A T T U A G G C A T A C C G G C DNA strands pulled apart T Amino acids attached to tRNA Polypeptide chain tRNA molecules can pick up another molecule of the same amino acid and be reused G 5 At the end of the mRNA, the ribosome releases the new protein Nuclear pore 1 DNA information is copied, or transcribed, into mRNA following complementary base pairing Messenger RNA G C Transcription (in nucleus) DNA strand G C C G A T C G G C C G U C A G 4 As the ribosome moves along the mRNA, more amino acids are added Translation (in cytoplasm) Amino acids represented A U G G G C U C C G C A A C G G C A G G C Codon 1 Methionine Codon 2 Glycine Codon 3 Serine Codon 4 Alanine Codon 5 Threonine Codon 6 Alanine Codon 7 Glycine 45 Protein Synthesis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 The transfer RNA molecule for the last amino acid added holds the growing polypeptide chain and is attached to its complementary codon on mRNA. 1 2 Growing polypeptide chain Anticodon 3 4 Next amino acid 5 6 Transfer RNA UGCCGU A U GGGC U C CGC A A CGGCA GGC A A GC GU 1 2 3 4 5 6 7 Codons 2 A second tRNA binds complementarily to the next codon, and in doing so brings the next amino acid into position on the ribosome. A peptide bond forms, linking the new amino acid to the growing polypeptide chain. 1 2 Growing polypeptide chain Peptide bond 3 4 Next amino acid 5 6 Transfer RNA Anticodon UGCCGU A U GGGC U C CGC A A CGGCA GGC A A GC GU 1 2 3 2 3 4 5 6 Messenger RNA 7 Codons 1 3 The tRNA A molecule that brought the last amino acid to the ribosome is released to the cytoplasm, and will be used again. The ribosome moves to a new position at the next codon on mRNA. 4 5 7 Next amino acid 6 Transfer RNA CGU A U GGGC U C CGC A A CGGCA GGC A A GC GU 1 2 3 4 5 6 7 Messenger RNA Ribosome 1 4 A new tRNA complementary to the next codon on mRNA brings the next amino acid to be added to the growing polypeptide chain. 2 3 4 5 6 7 Next amino acid Transfer RNA CGU CCG A U GGGC U C CGC A A CGGCA GGC A A GC GU 1 2 3 4 5 6 7 Messenger RNA 46 Animation: Protein Synthesis Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 47 4.3 From Science to Technology MicroRNAs and RNA Interference 48 4.7: Changes in Genetic Information • Only about 1/10th of one percent of the human genome differs from person to person 49 Nature of Mutations • Mutations – change in genetic information • Result when: • Extra bases are added or deleted • Bases are changed • May or may not change the protein Direction of “reading” code Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Code for glutamic acid T P Mutation P S P P S A S C P S (a) T S T P Code for valine C S (b) 50 Protection Against Mutation • Repair enzymes correct the mutations 51 Inborn Errors of Metabolism • Occurs from inheriting a mutation that then alters an enzyme • This creates a block in an otherwise normal biochemical pathway 52 4.4 From Science to Technology The Human Metabolome 53 Important Points in Chapter 4: Outcomes to be Assessed 4.1: Introduction Define metabolism. Explain why protein synthesis is important. 4.2: Metabolic Processes Compare and contrast anabolism and catabolism. Define dehydration synthesis and hydrolysis. 4.3: Control of Metabolic Reactions Describe how enzymes control metabolic reactions. List the basic steps of an enzyme-catalyzed reaction. Define active site. 54 Important Points in Chapter 4: Outcomes to be Assessed Define a rate-limiting enzyme and indicate why it is important in a metabolic pathway. 4.4: Energy for Metabolic Reactions Explain how ATP stores chemical energy and makes it available to a cell. State the importance of the oxidation of glucose. 4.5: Cellular Respiration Describe how the reactions and pathways of glycolysis, the citric acid cycle, and the electron transport chain capture the energy in nutrient molecules. Discuss how glucose is stored, rather than broken down. 55 Important Points in Chapter 4: Outcomes to be Assessed 4.6: Nucleic Acids and Protein Synthesis Define gene and genome. Describe the structure of DNA, including the role of complementary base pairing. Describe how DNA molecules replicate. Define genetic code. Compare DNA and RNA. Explain how nucleic acid molecules (DNA and RNA) carry genetic information. Define transcription and translation. Describe the steps of protein synthesis. 56 Important Points in Chapter 4: Outcomes to be Assessed 4.7: Changes in Genetic Information Compare and contrast mutations and SNPs. Explain how a mutation can cause a disease. Explain two ways that mutations originate. List three types of genetic changes. Discuss two ways that DNA is protected against mutation. 57 Quiz 4 Complete Quiz 4 now! Read Chapter 5. 58