Chapter 4 Cellular Metabolism 4.1: Introduction Metabolic processes: All chemical reactions that occur in the body There are two 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 2 Anabolism Anabolism provides the materials needed for cellular growth and repair Dehydration Synthesis Type of anabolic process Produces water Used to make polysaccharides, triglycerides, nucleic acids & proteins 3 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 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 4 Water Anabolism & Catabolism 5 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 Substrate molecules Product molecule Active site Enzyme molecule (a) Enzyme-substrate complex (b) (c) Unaltered enzyme molecule 6 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 Substrate 1 Enzyme A Enzyme B Substrate Enzyme names commonly: 2 Substrate 3 Enzyme C Substrate 4 Enzyme D Product Reflect the substrate Have the suffix – ase Examples: sucrase, lactase, protease, lipase 7 Cofactors and Coenzymes Cofactors Make some enzymes active Non-protein component Ions or coenzymes Coenzymes Organic molecules that act as cofactors Vitamins 8 Factors That Alter Enzymes Factors that alter enzymes: Heat Radiation Electricity Chemicals Changes in pH 9 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). 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Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 10 Regulation of Metabolic Pathways Limited number of regulatory enzymes Negative feedback Inhibition Rate-limiting Enzyme A Substrate Substrate 2 1 Enzyme B Substrate 3 Enzyme C Substrate 4 Enzyme D Product 11 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 12 ATP Molecules Each ATP molecule has three parts: An adenine molecule A ribose molecule Three phosphate molecules in a chain Third phosphate attached by high-energy bond When the bond is broken, energy is transferred When the bond is broken, ATP becomes ADP ADP becomes ATP through phosphorylation Phosphorylation requires energy release from cellular respiration 4.5: Cellular Respiration Occurs in a series of reactions: Glycolysis “Prep” steps or intermediate steps Citric acid cycle (aka TCA or Kreb’s Cycle) Electron transport system 14 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 15 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 3 Events: Phosphorylation Splitting Production of NADH and ATP 16 Glycolysis Event 1 – Phosphorylation Glucose Phase 1 priming Carbon atom P Phosphate Two phosphates added to glucose Requires ATP 2 ATP 2 ADP Fructose-1,6-diphosphate P P Event 2 – Splitting (cleavage) 6-carbon glucose split into two 3carbon molecules 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) 17 Glycolysis Event 3:Production of NADH and ATP Glucose Phase 1 priming Carbon atom P Phosphate 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 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) 18 Anaerobic Reactions If oxygen is NOT available: Glucose Phase 1 priming Carbon atom P Phosphate 2 ATP Electron transport system cannot accept new electrons from NADH 2 ADP Fructose-1,6-diphosphate P P Phase 2 cleavage Dihydroxyacetone phosphate P Pyruvic acid is converted to lactic acid 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 Glycolysis is inhibited O2 2 NADH + H+ 2 NAD+ 2 Lactic acid To citric acid cycle and electron transport chain (aerobic pathway) 19 Aerobic Reactions 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 20 Citric Acid Cycle Copyright © The McGraw-Hill Companies, Inc. 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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 For each citric acid molecule: One ATP is produced Eight hydrogen atoms are transferred to NAD+ and FAD Two CO2 produced 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+ 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 21 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 ADP + P ATP synthase ATP Energy NADH + H+ Energy 2H+ + 2e– NAD+ Energy FADH2 2H+ + 2e– FAD Electron transport chain 2e– 2H+ O2 22 H2O Summary of Cellular Respiration Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glucose Glycolysis The 3-carbon pyruvic acids generated by glycolysis enter the mitochondria. Each loses a carbon (generating CO2 and 2 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 3 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 series4of 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. High-energy electrons (e–) 2 ATP Cytosol Glycolysis Pyruvic acid Pyruvic acid High-energy electrons (e–) CO2 Acetyl CoA Citric acid Oxaloacetic acid Mitochondrion The 6-carbon sugar glucose is broken down in the 1 cytosol into two 3-carbon pyruvic acid molecules with a net gain of 2 ATP and release of high-energy electrons. Citric Acid Cycle Citric acid cycle High-energy electrons (e–) 2 CO2 2 ATP Electron transport chain 32–34 ATP 2e– and 2H+ O2 H2O 23 Carbohydrate Storage Carbohydrate molecules from foods can enter: Catabolic pathways for energy production Anabolic pathways for storage 24 Carbohydrate Storage Excess glucose stored as: Glycogen (primarily by liver and muscle cells) Fat Converted to amino acids Carbohydrates from foods Hydrolysis Monosaccharides Catabolic pathways Anabolic pathways Energy + CO2 + H2O Glycogen or Fat Amino acids 25 Summary of Catabolism of Proteins, Carbohydrates, and Fats 29 4.6: Nucleic Acids and Protein Synthesis Instruction of cells to synthesize proteins comes from a nucleic acid, DNA 27 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 28 Structure of DNA Two polynucleotide chains – double-stranded Hydrogen bonds hold nitrogenous bases together Bases pair specifically (A-T and C-G) Forms a helix DNA wrapped about histones forms chromatin chromosomes are condensed chromatin Animation:DNA Structure https://www.youtube.com/watch?v=qy8dk5iS1f0&safe=active 29 DNA Replication Hydrogen bonds break between bases Double strands unwind and pull apart New nucleotides pair with exposed bases Controlled by DNA polymerase Animation:DNA Replication https://www.youtube.com/watch?v=27TxKoFU2Nw 30 Genetic Code Specification of the correct sequence of amino acids in a polypeptide chain Each amino acid is represented by a triplet code 31 RNA Molecules Single-standed Ribose Uracil Instead Of Thymine 32 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 33 RNA Molecules Messenger RNA (mRNA): Delivers genetic information from nucleus to the cytoplasm Single polynucleotide chain Formed beside a strand of DNA RNA nucleotides are complementary to DNA nucleotides (exception – no thymine in RNA; replaced with uracil) 34 Animation:Stages of Transcription https://www.youtube.com/watch?v=WsofH466lqk 35 Animation:How Translation Works https://www.youtube.com/watch?v=5bLEDd-PSTQ Protein Synthesis 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 3 Growing polypeptide chain Anticodon 1 4 Next amino acid 5 6 Transfer RNA UGCCGU AU GGGC U C CGC AA CGGCA GGC A A GC GU 1 2 3 4 5 6 7 Codons 1 2 Growing polypeptide chain 2 A second tRNA binds complementarily to the next codon, and in doing so brings the next amino acid into position on the ribosome. Peptide bond 3 4 Next amino acid 5 6 Transfer RNA Anticodon UGCCGU AU GGGC U C CGC AA CGGCA GGC A A GC GU The tRNA 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. 1 2 3 2 3 4 5 6 Messenger RNA 7 Codons 1 3 A 4 5 7 Next amino acid 6 A peptide bond forms, linking the new amino acid to the growing polypeptide chain Transfer RNA CGU AU GGGC U C CGC AA CGGCA GGC A A GC GU 1 2 3 4 5 6 7 Messenger RNA Ribosome 1 2 4 3 4 5 6 7 Next amino acid Transfer RNA CGU CCG AU GGGC U C CGC AA CGGCA GGC A A GC GU 1 2 3 4 5 6 7 Messenger RNA A new tRNA complementary tothe next codon on mRNA brings the next amino acid to be added to the growing polypeptide chain 36 . 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 37 Protection Against Mutation Repair enzymes correct the mutations Inborn Errors of Metabolism Occurs from inheriting a mutation that then alters an enzyme This creates a block in an otherwise normal biochemical pathway 38