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Metabolism Anatomy and Physiology | Tutorial Notes Cell Metabolism LEARNING OBJECTIVES After study of this chapter, the student will: 1. Compare and contrast anabolism and catabolism 2. Describe the role of enzymes in metabolic reactions. 3. Explain how metabolic pathways are regulated. 4. Explain how ATP stores chemical energy and makes it available to a cell. 5. Explain how the reactions of cellular respiration release chemical energy. 6. Describe the general metabolic pathways of carbohydrate metabolism. 7. Describe how DNA molecules store genetic information. 8. Explain how protein synthesis relies on genetic information. 9. Compare and contrast DNA and RNA 10. Describe the steps of DNA synthesis. 11. Describe the steps of protein synthesis. 12. Describe how genetic information can be altered. 13. Explain how a mutation may or may not affect an organism. TUTORIAL OUTLINE I. Metabolism – sum of all chemical reactions in a cell. A. Anabolism – synthesis of large molecules from smaller ones. B. Anabolic reactions requires cellular energy Catabolism – decomposition of larger molecules into smaller ones. Catabolic reactions release energy o About 60% is released as heat o About 40% is used to drive activities within the cell 1 Metabolism II. III. Dehydration Synthesis (see figures 4.1 - 4.3) A. Dehydration synthesis is an example of an anabolic reaction. B. Water is released as molecules are joined together. C. Examples of dehydration synthesis include: 1. Formation of polysaccharides from monosaccharides 2. Formation of polypeptides (proteins) from amino acids 3. Formation of polynucleotides (nucleic acids) from nucleotides 4. Formation of fats (triglycerides) by attaching 3 fatty acids to glycerol. Hydrolysis (see figures 4.1 - 4.3) A. Hydrolysis is an example of a catabolic reaction B. Water is consumed as molecules are broken apart C. Examples of hydrolysis include: 1. Decomposition of polysaccharides into monosaccharides 2. Decomposition of polypeptides (proteins) into amino acids 3. Decomposition of polynucleotides (nucleic acids) into nucleotides 4. Decomposition of fats (triglycerides) by removing fatty acids from glycerol By Created by TimVickers, vectorized by Fvasconcellos (Provided by TimVickers) [Public domain], via Wikimedia Commons http://upload.wikimedia.org/wikipedia/commons/a/af/213_Dehydration_Synthesis_and_Hydrolysis-01.jpg 2 Metabolism IV. Enzymes A. Characteristics of Enzymes 1. Enzymes are biological catalysts (increase the rate of reaction without being consumed) 2. Most enzymes are proteins 3. Enzymes are required in small amounts, because they are not consumed (reusable) 4. Enzymes have high specificity – act on only one substrate B. a substrate is the target molecule of an enzyme 5. Most enzymes are named for the substrate they act on 6. Many enzymes end with the suffix –ase a. protease – splits proteins b. nuclease – splits nucleic acids c. lipase – splits lipids d. amylase – splits starch (a polysaccharide) e. lactase – splits lactose (a disaccharide) f. ATPase – splits ATP (currency of energy), releasing energy + ADP + Phosphate g. ATPsynthase – makes new ATP, by attaching a phosphate to ADP Activation Energy 1. Activation energy is the amount of energy required to initiate a chemical reaction 2. Enzymes work by reducing the activation energy of a chemical reaction By Fvasconcellos (talk · contribs) (Image:Activation2 updated.svg) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons http://upload.wikimedia.org/wikipedia/commons/f/fe/Carbonic_anhydrase_reaction_in_tissue.svg 3 Metabolism C. D. ‘ E. F. Enzyme-Catalyzed Reactions 1. Active site - the part of an enzyme the substrate binds to. 2. Enzyme-substrate complex temporarily forms when the substrate(s) bind to the enzyme. 3. The enzyme catalyzes the reaction, then releases the product. 4. The unchanged enzyme is used in a new chemical reaction. Limits to the rate of enzyme catalyzed reactions: 1. Concentration of the enzyme 2. Concentration of the substrate 3. Efficiency of the enzyme Metabolic Pathways 1. Metabolic Pathway is a series of enzyme-catalyzed reactions within a cell. 2. The product of each reaction is used as a substrate for the next reaction. 3. Each reaction requires a separate enzyme 4. Rate-Limiting Enzyme is the least efficient enzyme in the metabolic pathway Cofactors and Coenzymes 1. Cofactor – ion or molecule that improves the efficiency of an enzyme. a. Inorganic cofactors include: Fe2+, Cu2+, Zn2+ b. Coenzymes are organic cofactors Vitamins are coenzymes that cannot be synthesized in sufficient quantities, so they are obtained through the diet. 4 Metabolism V. Energy: is the ability to do work (or capacity to cause change) A. B. Examples of energy include: 1. chemical 2. thermal 3. mechanical 4. electrical 5. nuclear Law of Conservation of Energy: Within a closed system, energy can be converted (first law of thermodynamics) from one form to another, but it cannot be created or destroyed. 1. C. Example: combustion of gasoline in an automobile transfers chemical energy in the covalent bonds of gasoline into heat and mechanical energy. Cell Respiration: is the process of converting the chemical energy in food molecules (such as glucose) into a form the cell can use (ATP). Cell Respiration Reaction of 1 glucose molecule C6H12O6 + 6O2 → 6CO2 + 6H2O (glucose) VI. + energy for 36-38 ATP ATP: Adenosine Triphosphate A. ATP is a molecule that carries energy in a form the cell can use (currency of energy for a cell) B. The third Phosphate of ATP can be hydrolyzed, releasing energy the cell can use. C. Hydrolysis of ATP produces ADP (Adenosine Diphosphate) + P + free energy D. The free energy is harnessed by the cell to do work or drive chemical reactions. ATP is decomposed, releasing energy for cell activity Energy released for cell activity 5 Metabolism Cell Respiration attaches Phosphate to ADP, making a new molecule of ATP Energy from cellular respiration ATP is formed by harnessing the energy released from the controlled breakdown (oxidation) of organic molecules (food), and using that energy to phosphorylate ADP. VI. Oxidative Phosphorylation: Cells obtain energy by the oxidation of organic molecules A. Oxidation: refers to the transfer of electrons from a molecule, in this case glucose, to a final electron acceptor, oxygen. 1. The oxidation (controlled breakdown) of glucose releases energy. The cells capture about half the energy to produce new ATP. The rest is released as heat. 2. As glucose is broken down (oxidized), electrons from the glucose are attached to electron carriers that transport them to the electron transport chain in the mitochondrion 3. Electron Carriers include: NADH & FADH2 2 electrons are transferred to NAD+ B. C. NAD+ + 2 H NADH + H FAD FADH2 + 2H Phosphorylation: Energy from the transfer of electrons is used to attach the phosphate to ADP, making new ATP 1. NADH is worth 3 ATP in the electron transport chain 2. FADH2 is worth 2 ATP in the electron transport chain Oxygen is the final electron acceptor. 6 Metabolism VII. VIII. The 3 Metabolic Pathways of Cell Respiration Are: A. Glycolysis B. Citric Acid Cycle C. Electron Transport Chain Glycolysis (Anaerobic Respiration) A. B. Overview 1. Glycolysis is anaerobic respiration – does not require oxygen. 2. Glycolysis occurs in the cytosol of the cell. 3. During Glycolysis 1 molecule of glucose is hydrolyzed into 2 molecules of pyruvic acid. Reactions of Glycolysis Phase 1 : Phosphorylation 2 ATP attach their phosphate to glucose, forming a 6-carbon sugar diphosphate. Phase 2: Cleavage Enzymes cleave the 6-carbon sugar molecule into 2 molecules of 3-carbon each. Phase 3: Oxidation Both 3-carbon molecules are oxidized (electrons are removed) forming 2 pyruvic acid molecules. 4 ATP and 2 NADH are gained from the reaction. C. Products of Glycolysis include: 2 molecules of Pyruvic Acid 2 molecules of ATP (net gain): (4 ATP are produced, but phase 1 consumes 2 ATP, so there’s a net gain of just 2 ATP) 2 molecules of NADH (each NADH is worth 3 ATP in the ETC) 7 Metabolism D. IX. Respiration under Anaerobic Vs. Aerobic Conditions 1. Aerobic Conditions: Under Aerobic conditions (when oxygen is sufficient), the pyruvic acid enters the mitochondria where it is further oxidized through aerobic respiration. 2. Anaerobic Conditions: Under Anaerobic conditions (where oxygen is not sufficient, such as during vigorous exercise) the pyruvic acid is converted into lactic acid in the cytosol a. NADH (produced from glycolysis) transfers its electrons to pyruvic acid, thus making NAD+ available again so it can accept electrons from additional glucose molecules. b. By receiving the electrons, pyruvic acid is converted into Lactic Acid c. As Lactic Acid accumulates in the cell, respiration becomes increasingly difficult. d. When oxygen is available again (eg. Following exercise) lactic acid is converted back into pyruvic acid, where it can continue through the aerobic pathway. Aerobic Respiration Overview A. Aerobic respiration occurs within the mitochondria 1. 2. The mitochondrion is bordered by a two membranes a. Outer membrane b. Inner Membrane – highly folded into folds, called Cristae Matrix: Space within the mitochondria 8 Metabolism translated by Ethan Gray, original by LadyofHats (File:Animal mitochondrion diagram en.svg) [Public domain], via Wikimedia Commons http://commons.wikimedia.org/wiki/File%3AAnimal_mitochondrion_diagram_fr.svg X. B. The Citric Acid Cycle occurs within the matrix of the mitochondrion C. The Electron Transport Chain occurs along the cristae of the mitochondrion Citric Acid Cycle (CAC) A. Priming for CAC: Pyruvic Acid is converted into Acetyl CoA before it enters the CAC. 1. B. 1 carbon is removed from pyruvic acid (decarboxylation), forming a 2-carbon acetic acid. The carbon is released as CO2 1 NADH is produced during this reaction. 2. Coenzyme A is attached to acetic acid, forming Acetyl CoA 3. Acetyl CoA is the substrate for the Citric Acid Cycle. Reactions of Citric Acid Cycle 1. Acetyl CoA enters the CAC when Coenzyme A releases the 2-carbon Acetic acid, which combines with a 4-carbon molecule (oxaloacetic acid) to form a 6-carbon Citric Acid. 2. Citric Acid is broken down through a series of reactions into a new 4-carbon molecule of oxaloacetic acid 3. Products of the CAC include: 2 molecules of CO2 1 molecule of ATP 3 molecules of NADH (NAD+ captures electrons from the citric acid) 1 molecule of FADH2 (FAD captures electrons from the citric acid) 9 Metabolism C. Each Glucose molecule requires 2 turns of the Citric Acid Cycle to be completely oxidized. 1. The breakdown of glucose in glycolysis produces 2 molecules of pyruvic acid. 2. Each molecule of pyruvic acid enters into the Citric Acid Cycle. 3. Therefore, the products of the CAC for 1 glucose are: 4 molecules of CO2 2 ATP 6 NADH (worth about 3 ATP each) 2 FADH2 (worth 2 ATP each) 10 Metabolism XI. Electron Transport Chain (ETC) (Oxidative Phosphorylation) A. The ETC consists of a series of enzymes along the cristae of the inner mitochondrial membrane 1. Complex proteins: are a chain of enzymes that transfer electrons from NADH (and FADH2) to a final electron acceptor (oxygen) 2. B. Energy from the transfer of electrons is used to power ATPSynthase ATP Synthase: synthesizes ATP by adding a phosphate to ADP Reactions of the ETC 1. The first complex protein removes electrons from NADH (and FADH2). 2. Electrons (e-) are transferred along the protein complexes of the ETC to the final electron acceptor (oxygen) 3. Energy from the e- transfer is used to pump H+ (protons) into the inner membrane space (via proton pumps). 4. The proton gradient generated by the H+ pumps is used to power ATP synthase. 5. ATP synthase phosphorylizes (adds a phosphate) ADP to generate new ATP. 6. Oxygen removes e- from the last complex protein, i.e. oxygen is the final electron acceptor. 7. Oxygen reacts with H+ and e- to form water. ( ½ O2 + 2H+ + 2 e- → H2O ) By OpenStax College [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons http://upload.wikimedia.org/wikipedia/commons/2/27/2508_The_Electron_Transport_Chain.jpg 11 Metabolism C. XI. Products of the ETC 1. 32 – 34 ATP are produced per each glucose molecule. 2. Water is produced as a bi-product Metabolic Pathways of carbohydrates A. Sugars produced from hydrolysis of carbohydrates may be broken down via cell respiration for energy. B. Or sugars may be used in anabolic reactions to synthesize other molecules. B 1. Glycogen – storage form of energy. Glycogen is broken down between meals to release glucose, when sugar levels become low. 2. Fats – when a person takes in more carbohydrates than are needed, the excess glucose is reacted to form fat molecules. Cell Respiration: Alternatives to glucose 1. Lipids and proteins may also be broken down to release energy for ATP production. DNA SYNTHESIS AND PROTEIN SYNTHESIS I. II. Genetic Inheritance Definitions A. Genetic Code: 3-letter DNA sequence that encodes for 1 amino acid (the building blocks of proteins) B. Gene: Sequence of DNA that encodes for 1 protein. C. Genome: Entire set of genetic instructions for an organism o The human genome is encoded on 23 pairs of chromosomes (46 total) o Human cells are diploid: 23 maternal & 23 paternal chromosomes o The human genome consists of around 20,000 genes. Protein Synthesis Overview A. DNA Replication: (DNA Synthesis) Sequence of original DNA is used as a template to make a new DNA molecule. Replication DNA (template) 12 DNA (new strand) Metabolism B. Protein Synthesis: DNA is used as a template to synthesize a protein. Transcription DNA III. IV. Translation RNA protein Structure of DNA (deoxyribonucleic acid) A. DNA is a double-stranded nucleic acid. B. The two strands are aligned in anti-parallel arrangement. C. The sugar of DNA is deoxyribose. D. DNA has 4 bases: Adenine (A), Thymine (T), Cytosine (C), and Guanine (G) E. A & G are purines (consist of 2 organic rings; C & T are pyrimidines (consists of 1 organic ring) F. Watson-Crick Base Pairs: A purine pairs with a pyrimidine A – T form a complementary base pair (stabilized by 2 Hydrogen bonds) C – G form a complementary base pair (stabilized by 3 Hydrogen bonds) Structure of RNA (ribonucleic acid) A. RNA is a single-stranded nucleic acid. B. The sugar of RNA is ribose. C. RNA has 4 bases: Adenine (A), Uracil (U), Cytosine (C), and Guanine (G) D. E. Note that RNA incorporates Uracil, instead of Thymine. Watson-Crick Base Pairs for RNA: A – U form a complementary base pair (stabilized by 2 Hydrogen bonds) C – G form a complementary base pair (stabilized by 3 Hydrogen bonds) There are many types of RNA: 1. messenger RNA (mRNA): Carries the information for protein synthesis from DNA to the ribosome 2. transfer RNA (tRNA): Carries amino acids for protein synthesis to the ribosome 3. ribosomal RNA (rRNA): Component of the ribosome, essential for protein synthesis 13 Metabolism DNA Vs. RNA V. DNA RNA Sugar Deoxyribose Ribose Strands Double-stranded Single-stranded Bases T,A,C,G U,A,C,G DNA Replication A. DNA replication occurs during S-phase (part of interphase). The cell makes a copy of its genome in preparation of cell division. B. Steps involved in DNA replication include: 1. Enzymes (called helicases) unwind and separate a portion of the DNA molecule, forming a replication bubble. 2. For each strand of the DNA molecule, an enzyme DNA Polymerase synthesizes a new complimentary strand of DNA, by assembling nucleotides along the sugar-phosphate backbone. 3. DNA polymerase uses the original strand as a template to build the new strand of DNA. Example: If the template strand is: TACTAGGTAC, then DNA Polymerase synthesizes: ATGATCCATG Because the two strands of a DNA molecule are anti-parallel, the two strands are replicated in opposite directions. Leading strand – is synthesized continuously Lagging strand – is synthesized discontinuously 4. DNA replication is semi-conservative: Each new molecule of DNA consists of 1 new strand and 1 original strand. Madprime [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by 14 Metabolism sa/3.0/) or CC BY-SA 2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/2.5-2.0-1.0)], via Wikimedia Commons http://upload.wikimedia.org/wikipedia/commons/3/33/DNA_replication_split_horizontal.svg 5. V. Transcription: Synthesis of mRNA from a DNA template A. Transcription occurs in the nucleus. B. An enzyme, called RNA Polymerase synthesizes a molecule of mRNA from the DNA. The RNA Polymerase reads the DNA template, and synthesizes a complimentary strand of mRNA. 1. VI. The two strands of DNA separate during mitosis. Example: if the DNA template is TTACGAATC, then the mRNA transcript will be AAUGCUUAG C. The mRNA is processed, then transported out of the nucleus into the cytoplasm, where it associates with ribosomes. D. Ribosomes “read” the mRNA sequence, and use it to synthesize a protein in a process called, translation. Translation: Synthesis of a protein from a mRNA sequence. A. Codon: 3-letter mRNA sequence that encodes for 1 amino acid. 1. Example: AUG – encodes for the amino acid Methionine. AUG is the “start” codon, because it initiates translation. 2. There are 20 amino acids encoded by 64 possible codons. 3. Stop Codon: A codon that does not encode for an amino acid terminates translation. By Thomas Splettstoesser (www.scistyle.com) (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons http://upload.wikimedia.org/wikipedia/commons/6/6d/RNA-codons-aminoacids.svg 15 Metabolism B. tRNA: Transfer RNA (tRNA) transports amino acids to the mRNA during translation. 1. Amino Acids are attached to one end of the tRNA. Amino acids are the building blocks of proteins. 2. Anticodon: is a 3-nucleotide base sequence on the other end of tRNA. The anticodon temporarily binds to a complimentary codon of mRNA during translation. Amino acid William Reusch CC BY-SA 3.0. https://www.boundless.com/users/235424/textbooks/virtual-textbook-oforganic-chemistry/biochemicals-9/nucleic-acids-54/rna-and-protein-synthesis-218-16105/ C. Ribosome: 1. Small particle of protein and rRNA. 2. Ribosomes have 2 subunits. a. Large Subunit: Binds the tRNA with its amino acid. b. Small Subunit binds to mRNA and “reads” the codon sequence. (i) The Acceptor (A) site – accepts new tRNA. The anticodons of tRNA form Hydrogen bonds with the complementary codons of mRNA. (ii) The Peptidyl (P) site – joins amino acids by a peptide bond when both the A and P site are occupied by tRNA. 16 Metabolism D. Sequence of translation: 1. A ribosome binds to the mRNA near the beginning of the messenger strand. Translation begins when a start codon (AUG) of the mRNA occupies the A-site of the ribosome. 2. A tRNA carrying an amino acid temporarily attaches itself to the mRNA, by binding its anticodon to the complimentary codon of the mRNA. 3. The ribosome moves forward one codon, so the start codon (along with its tRNA) occupies the P-site, and the next codon on the mRNA occupies the A-site. 4. A second tRNA carries an amino acid to the A-site, so both the P-site and A-site are occupied by tRNA. 5. A peptide bond is formed between the two amino acids, and the first tRNA is released. 6. The process repeats for each codon in the mRNA sequence as the ribosome moves along its length, forming a polypeptide chain. 7. When the ribosome reaches a STOP codon, the ribosome dissociates from the polypeptide chain. 8. Chaperone proteins fold the polypeptide chain into a functional protein. 9. The ribosomes, mRNA, and tRNA are recycled. By LadyofHats [Public domain], via Wikimedia Commons http://upload.wikimedia.org/wikipedia/commons/b/b1/Ribosome_mRNA_translation_en.svg 17 Metabolism VII. Changes in genetic information A. Nature of mutations. 1. B. Human genome sequences are 99.9% the same among individuals. a. Mutations: are rare distinctions in DNA sequence that effects how we look or feel. b. Single Nucleotide Polymorphisms (SNPs): More common genetic variants with no detectible effects. Mutations: also refers to the mechanism of change in a DNA sequence. 1. Mutations may result when extra bases within the DNA molecule are added, deleted, or changed. 2. Below: Examples of point mutations. A change in a single nucleotide base may or may not change the protein. By JonSta247, GFDL, via Wikimedia Commons http://commons.wikimedia.org/wiki/File:Point_mutations-en.png 18