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Chapter 4

Chapter 4. Energy and Cellular Metabolism. About this Chapter. Energy in biological systems Chemical reactions Enzymes Metabolism ATP production Synthetic pathways. Energy: Biological Systems. Energy transfer in the environment. KEY. Transfer of radiant or heat energy . Sun.

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Chapter 4

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  1. Chapter 4 Energy and Cellular Metabolism

  2. About this Chapter • Energy in biological systems • Chemical reactions • Enzymes • Metabolism • ATP production • Synthetic pathways

  3. Energy: Biological Systems • Energy transfer in the environment KEY Transfer of radiant or heat energy Sun Transfer of energy in chemical bonds Energy lost to environment Heat energy Radiant energy Energy for work CO2+ + Photosynthesis takes place in plant cells, yielding: Respiration takes place in human cells, yielding: Energy stored in biomolecules CO2 Energy stored in biomolecules + H2O CO2 N2 H2O Figure 4-1

  4. Energy: Capacity to Do Work • Chemical work • Making and breaking of chemical bonds • Transport work • Moving ions, molecules, and larger particles • Can create concentration gradients • Mechanical work • Used for movement

  5. Kinetic and Potential Energy Figure 4-2

  6. Thermodynamic Energy • First law of Thermodynamics • Total amount of energy in the universe is constant • Second law of Thermodynamics • Processes move from state of order to disorder

  7. Chemical Reactions: Overview • Activation energy is the energy that must be put into reactants before a reaction can proceed • A + B  C + D Figure 4-3

  8. Chemical Reactions: Exergonic and endergonic Activation energy Activation energy G+H A+B Net free energy change E+F Net free energy change C+D (b) Endergonic reactions (a) Exergonic reactions KEY Reactants Activation of reaction Reaction process Products Figure 4-4

  9. Chemical Reactions: Coupling Figure 4-5

  10. Enzymes: Overview • Isozymes • Catalyze same reaction, but under different conditions • May be activated, inactivated, or modulated • Coenzymes  vitamins • Chemical modulators  temperature and pH

  11. Enzymes: Lower activation energy KEY Reactants Activation energy Activation of reaction Reaction process Products A+B Net free energy change C+D Figure 4-6

  12. Enzymes: Law of Mass Action Figure 4-9a

  13. Enzymes: Law of Mass Action Figure 4-9b

  14. Enzymes: Types of Reactions Table 4-4

  15. Metabolism: Overview • A group of metabolic pathways resembles a road map Figure 4-10

  16. Metabolism: Cell Regulation • Controlling enzyme concentrations • Producing allosteric and covalent modulators • Using different enzymes for reversible reactions • Isolating enzymes within organelles • Maintaining optimum ratio of ATP to ADP

  17. Metabolism: Cell Regulation enzyme 1 enzyme 2 enzyme 3 Feedback inhibition Figure 4-11

  18. Metabolism: Cell Regulation + PO4 + + Glucose Glucose H2O CO2 PO4 carbonic anhydrase carbonic anhydrase glucose 6- phosphatase hexokinase hexokinase Carbonic acid Glucose 6-phosphate Glucose 6-phosphate (a) (b) (c) Figure 4-12

  19. ATP Production: Overview Glucose G L Y C O L Y S I S • Overview of aerobic pathways for ATP production ADP Glycerol ATP Amino acids Acetyl CoA Citric acid cycle Amino acids Pyruvate Cytosol High-energy electrons Mitochondrion Fatty acids Acetyl CoA ADP Amino acids CITRIC ACID CYCLE ATP CO2 High-energy electrons and H+ ADP ELECTRON TRANSPORT SYSTEM ATP O2 H2O Figure 4-13

  20. ATP Production: Glycolysis Glucose ATP ADP Glucose + 2 NAD++ 2 ADP + P  2 Pyruvate + 2 ATP + 2 NADH + 2 H++ 2 H20 Glucose 6-phosphate Fructose 6-phosphate ATP ADP Fructose 1,6-bisphosphate Dihydroxyacetone phosphate KEY = Carbon Glyceraldehyde 3-phosphate = Oxygen = Phosphate group NAD+ (side groups not shown) NADH 1, 3-Bisphosphoglycerate ADP ATP This section happens twice for each glucose molecule that begins glycolysis 3-Phosphoglycerate 2-Phosphoglycerate H2O Phosphoenol pyruvate ADP ATP Pyruvate Figure 4-14

  21. ATP Production: Pyruvate Metabolism • Pyruvate can be converted into lactate or acetyl CoA NADH NAD+ Anaerobic Aerobic Lactate Pyruvate Pyruvate Pyruvate Acetyl CoA NAD+ Cytosol NADH CO2 CoA Mitochondrial matrix Acetyl CoA CoA KEY = Carbon Acyl unit = Oxygen CoA = Coenzyme A CITRIC ACID CYCLE H and –OH not shown Figure 4-15

  22. ATP Production: Citric Acid Cycle • Acetyl CoA enters the citric acid cycle producing3 NADH, 1 FADH2, and 1 ATP KEY = Carbon = Oxygen CoA = Coenzyme A Side groups not shown Acetyl CoA CoA CoA Citrate (6C) Oxaloacetate (4C) NADH Isocitrate (6C) NAD+ Malate (4C) NAD+ Acetyl CoA CO2 NADH CITRIC ACID CYCLE Citric acid cycle H2O a Ketoglutarate (5C) High-energy electrons Fumarate (4C) NAD+ CO2 FADH2 NADH ATP FAD CoA ADP Succinate (4C) Succinyl CoA (4C) CoA GTP GDP + Pi CoA Figure 4-16

  23. ATP Production: Electron Transport Mitochondrial matrix CITRIC ACID CYCLE Inner mitochondrial membrane + 2 H2O Matrix pool of H+ O2 e– 3 1 ATP ADP + Pi 4 4e– High-energy electrons ATP synthase H+ H+ H+ 2 H+ Intermembrane space H+ H+ H+ ELECTRON TRANSPORT SYSTEM Outer mitochondrial membrane High-energy electrons from glycolysis Cytosol 2 3 4 1 Potential energy captured in the H+ concentration gradient is converted to kinetic energy when H+ ions pass through the ATP synthase. Some of the kinetic energy is captured as ATP. Energy released during metabolism is captured by high-energy electrons carried by NADH and FADH2. Energy from high-energy electrons moving along the electron transport system pumps H+ from the matrix into the intermembrane space. Electrons at the end of the electron transport system are back to their normal energy state. They combine with H+ and oxygen to form water. Figure 4-17

  24. ATP Production: Electron Transport Mitochondrial matrix CITRIC ACID CYCLE Inner mitochondrial membrane e– 1 High-energy electrons Intermembrane space ELECTRON TRANSPORT SYSTEM Outer mitochondrial membrane High-energy electrons from glycolysis Cytosol 1 Energy released during metabolism is captured by high-energy electrons carried by NADH and FADH2. Figure 4-17, step 1

  25. ATP Production: Electron Transport Mitochondrial matrix CITRIC ACID CYCLE Inner mitochondrial membrane e– 1 e– High-energy electrons H+ H+ H+ 2 Intermembrane space H+ H+ H+ ELECTRON TRANSPORT SYSTEM Outer mitochondrial membrane High-energy electrons from glycolysis Cytosol 2 1 Energy released during metabolism is captured by high-energy electrons carried by NADH and FADH2. Energy from high-energy electrons moving along the electron transport system pumps H+ from the matrix into the intermembrane space. Figure 4-17, steps 1–2

  26. ATP Production: Electron Transport Mitochondrial matrix CITRIC ACID CYCLE Inner mitochondrial membrane + 2 H2O Matrix pool of H+ O2 e– 3 1 4e– High-energy electrons H+ H+ H+ 2 Intermembrane space H+ H+ H+ ELECTRON TRANSPORT SYSTEM Outer mitochondrial membrane High-energy electrons from glycolysis Cytosol 2 3 1 Energy released during metabolism is captured by high-energy electrons carried by NADH and FADH2. Energy from high-energy electrons moving along the electron transport system pumps H+ from the matrix into the intermembrane space. Electrons at the end of the electron transport system are back to their normal energy state. They combine with H+ and oxygen to form water. Figure 4-17, steps 1–3

  27. ATP Production: Electron Transport Mitochondrial matrix CITRIC ACID CYCLE Inner mitochondrial membrane NADH and FADH2  ATP by oxidative phosphorylation + 2 H2O Matrix pool of H+ O2 e– 3 1 ATP ADP + Pi 4 4e– High-energy electrons ATP synthase H+ H+ H+ 2 H+ Intermembrane space H+ H+ H+ ELECTRON TRANSPORT SYSTEM Outer mitochondrial membrane High-energy electrons from glycolysis Cytosol 2 3 4 1 Potential energy captured in the H+ concentration gradient is converted to kinetic energy when H+ ions pass through the ATP synthase. Some of the kinetic energy is captured as ATP. Energy released during metabolism is captured by high-energy electrons carried by NADH and FADH2. Energy from high-energy electrons moving along the electron transport system pumps H+ from the matrix into the intermembrane space. Electrons at the end of the electron transport system are back to their normal energy state. They combine with H+ and oxygen to form water. Figure 4-17, steps 1–4

  28. ATP Production: Energy Yield AEROBIC METABOLISM ANAEROBIC METABOLISM C6H12O6 2 C3H6O3 (Lactic acid) C6H12O6 + 6 O2 6 CO2 + 6 H2O NADH FADH2 ATP CO2 NADH FADH2 ATP CO2 1 Glucose 1 Glucose G L Y C O L Y S I S G L Y C O L Y S I S 4 +4 2 2* –2 –2 2 Pyruvate 2 Pyruvate –2 2 2 2 Acetyl CoA 2 Lactic acid 2 ATP 0 NADH TOTALS Citric acid cycle 6 2 2 4 High-energy electrons and H+ 6 O2 ELECTRON TRANSPORT SYSTEM 26-28 30-32 ATP 6 CO2 6 H2O TOTALS * Cytoplasmic NADH sometimes yield only 1.5 ATP/NADH instead of 2.5 ATP/NADH. Figure 4-18

  29. ATP Production: Large Biomolecules • Glycogenolysis • Glycogen • Storage form of glucose in liver and skeletal muscle • Converted to glucose or glucose 6-phosphate

  30. ATP Production: Protein Catabolism and Deamination (b) Deamination (a) Protein catabolism NAD + H2O NADH + H+ NH3 + Ammonia Deamination Organic acid Amino acid Protein or Peptide H2O Hydrolysis of peptide bond Glycolysis or citric acid cycle (c) + Peptide Amino acid H+ NH3 Urea NH4+ Ammonium Ammonia Figure 4-20

  31. ATP Production: Lipolysis Triglyceride Glucose 1 Lipases digest triglycerides into glycerol and 3 fatty acids. 1 G L Y C O L Y S I S Glycerol 2 2 Glycerol becomes a glycolysis substrate. Fatty acid Pyruvate Cytosol 3 b-oxidation chops 2-carbon acyl units off the fatty acids. b-oxidation 3 CO2 Acetyl CoA CoA Acyl unit 4 4 Acyl units become acetyl CoA and can be used in the citric acid cycle. CoA CITRIC ACID CYCLE Mitochondrial matrix Figure 4-21

  32. Synthesis: Gluconeogenesis Glucose Liver, kidney Glucose synthesis Glucose 6- phosphate G L U C O N E O G E N E S I S GLYCEROL AMINO ACIDS Pyruvate AMINO ACIDS LACTATE Figure 4-22

  33. Synthesis: Lipids Glucose G L Y C O 1 L Y S I S Glycerol 3 Pyruvate Acetyl CoA Triglyceride Fatty acid synthetase 2 CoA Acyl unit Fatty acids 1 2 3 Glycerol can be made from glucose through glycolysis. Two-carbon acyl units from acetyl CoA are linked together by fatty acid synthetase to form fatty acids. One glycerol plus 3 fatty acids make a triglyceride. Figure 4-23

  34. Synthesis: Lipids Glucose G L Y C O 1 L Y S I S Glycerol Pyruvate Acetyl CoA CoA Acyl unit 1 Glycerol can be made from glucose through glycolysis. Figure 4-23, steps 1

  35. Synthesis: Lipids Glucose G L Y C O 1 L Y S I S Glycerol Pyruvate Acetyl CoA Fatty acid synthetase 2 CoA Acyl unit Acyl unit Fatty acids 1 2 Glycerol can be made from glucose through glycolysis. Two-carbon acyl units from acetyl CoA are linked together by fatty acid synthetase to form fatty acids. Figure 4-23, steps 1–2

  36. Synthesis: Lipids Glucose G L Y C O 1 L Y S I S Glycerol 3 Pyruvate Acetyl CoA Triglyceride Fatty acid synthetase 2 CoA Acyl unit Fatty acids 1 2 3 Glycerol can be made from glucose through glycolysis. Two-carbon acyl units from acetyl CoA are linked together by fatty acid synthetase to form fatty acids. One glycerol plus 3 fatty acids make a triglyceride. Figure 4-23, steps 1–3

  37. Synthesis: DNA to Protein Gene Regulatory proteins 1 GENE ACTIVATION Constitutively active Regulated activity Induction Repression 2 TRANSCRIPTION mRNA siRNA 3 mRNA PROCESSING Alternative splicing Interference mRNA “silenced” Processed mRNA Nucleus • rRNA in ribosomes • tRNA • Amino acids Cytoplasm 4 TRANSLATION Protein chain 5 POST-TRANSLATIONAL MODIFICATION Folding and cross-links Cleavage into smaller peptides Assembly into polymeric proteins Addition of groups: • sugars • lipids • -CH3 • phosphate Figure 4-25

  38. Synthesis: DNA to Protein Gene Regulatory proteins 1 GENE ACTIVATION Constitutively active Regulated activity Induction Repression Nucleus Cytoplasm Figure 4-25, steps 1

  39. Synthesis: DNA to Protein Gene Regulatory proteins 1 GENE ACTIVATION Constitutively active Regulated activity Induction Repression 2 TRANSCRIPTION mRNA Nucleus Cytoplasm Figure 4-25, steps 1–2

  40. Synthesis: DNA to Protein Gene Regulatory proteins 1 GENE ACTIVATION Constitutively active Regulated activity Induction Repression 2 TRANSCRIPTION mRNA siRNA 3 mRNA PROCESSING Alternative splicing Interference mRNA “silenced” Processed mRNA Nucleus Cytoplasm Figure 4-25, steps 1–3

  41. Synthesis: DNA to Protein Gene Regulatory proteins 1 GENE ACTIVATION Constitutively active Regulated activity Induction Repression 2 TRANSCRIPTION mRNA siRNA 3 mRNA PROCESSING Alternative splicing Interference mRNA “silenced” Processed mRNA Nucleus • rRNA in ribosomes • tRNA • Amino acids Cytoplasm 4 TRANSLATION Protein chain Figure 4-25, steps 1–4

  42. Synthesis: DNA to Protein Gene Regulatory proteins 1 GENE ACTIVATION Constitutively active Regulated activity Induction Repression 2 TRANSCRIPTION mRNA siRNA 3 mRNA PROCESSING Alternative splicing Interference mRNA “silenced” Processed mRNA Nucleus • rRNA in ribosomes • tRNA • Amino acids Cytoplasm 4 TRANSLATION Protein chain 5 POST-TRANSLATIONAL MODIFICATION Folding and cross-links Cleavage into smaller peptides Assembly into polymeric proteins Addition of groups: • sugars • lipids • -CH3 • phosphate Figure 4-25, steps 1–5

  43. Protein: Transcription RNA polymerase 1 RNA polymerase binds to DNA. 2 The section of DNA that contains the gene unwinds. RNA bases 3 RNA bases bind to DNA, creating a single strand of mRNA. Sense strand Site of nucleotide assembly DNA Lengthening mRNA strand Antisense strand RNA polymerase mRNA transcript 4 mRNA and the RNA polymerase detach from DNA, and the mRNA goes to the cytoplasm. RNA polymerase mRNA strand released Leaves nucleus after processing Figure 4-26

  44. Protein: Transcription Gene Sense strand Antisense strand Promoter Transcribed section DNA TRANSCRIPTION Unprocessed mRNA Introns removed Introns removed Exons for protein #1 Exons for protein #2 Figure 4-27

  45. Protein: Transcription and Translation DNA 1 Transcription RNA polymerase 2 Nuclear membrane mRNA processing 3 Attachment of ribosomal subunits Amino acid Incoming tRNA bound to an amino acid tRNA Growing peptide chain 4 Translation Outgoing “empty” tRNA Anticodon mRNA Ribosome mRNA 5 Termination Completed peptide Ribosomal subunits Figure 4-28

  46. Protein: Transcription and Translation DNA 1 Transcription RNA polymerase Nuclear membrane Figure 4-28, steps 1

  47. Protein: Transcription and Translation DNA 1 Transcription RNA polymerase 2 Nuclear membrane mRNA processing Figure 4-28, steps 1–2

  48. Protein: Transcription and Translation DNA 1 Transcription RNA polymerase 2 Nuclear membrane mRNA processing 3 Attachment of ribosomal subunits Figure 4-28, steps 1–3

  49. Protein: Transcription and Translation DNA 1 Transcription RNA polymerase 2 Nuclear membrane mRNA processing 3 Attachment of ribosomal subunits Amino acid Incoming tRNA bound to an amino acid tRNA Growing peptide chain 4 Translation Outgoing “empty” tRNA Anticodon mRNA Ribosome Figure 4-28, steps 1–4

  50. Protein: Transcription and Translation DNA 1 Transcription RNA polymerase 2 Nuclear membrane mRNA processing 3 Attachment of ribosomal subunits Amino acid Incoming tRNA bound to an amino acid tRNA Growing peptide chain 4 Translation Outgoing “empty” tRNA Anticodon mRNA Ribosome mRNA 5 Termination Completed peptide Ribosomal subunits Figure 4-28, steps 1–5

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