Ch 4: Energy and Cellular Metabolism

1. Ch 4: Energy and Cellular Metabolism • Energy as it relates to Biology • Chemical reactions • Enzymesand how they speed rxs • Metabolism and metabolic pathways • Catabolism (ATP production) • Anabolism (Synthesis of biologically important molecules)

2. Energy in Biological Systems Review on your own!

3. Substrates / reactants Products Chemical Reactions • Transfer energy • or use energy to do work A + B C + D Bioenergetics: Study of energy flow through biol. systems Reaction rate = speed of reaction

4. Activation Energy Starts Reaction Reversible (most biol. rxs.) vs. irreversible reactions Fig 4-3

5. Endergonic vs. Exergonic Reactions Coupling endergonic and exergoinic rxs Direct coupling vs. indirect coupling Which kind?

6. Enzymes are Proteins acting as Biological Catalysts 4 important characteristics of enzymes •  chemical reaction rate by lowering activation energy • are not changed themselves • do not change nature of rx nor result • are specific Fig 4-8

8. Enzymes lower activation energy: All chemical reactions in body must be conducted at body temp.!! How do enzymes lower activation energy ?

9. Enzymes bind to reactant molecules and bring them together in best position for rx.

10. Active Site: Small region of the complex 3D structure is active (or binding) site. Enzymes bind to substrate Old: Lock-and-key model / New: Induced-fit model Fig 2-16

11. Enzyme-substrate interaction: The old and the new model

12. Not in book Naming of Enzymes mostly suffix -ase first part gives info on function • Kinase • Phosphatase • Peptidase • Dehydrogenase examples

13. Isozymes=different models of same enzyme (differ in 1 or few aa) Examples: • Amylase • LDH → importance in diagnostics Catalize same reaction under different conditions and in different tissues/organs Review Table 4-3

14. Enzyme Activity depends on • proteolytic activation (for some) • cofactors & coenzymes (for some) • temperature • pH • other molecules interacting with enzyme

15. 1) Proteolytic Activation • Also • Pepsinogen Pepsin • Trypsinogen Trypsin

16. 2) Cofactors & Coenzymes structure: ___________ molecules (e.g. ?) function: conformational change of active site structure: Organic molecules (vitamin derivatives, FADH2 ....) function: act as receptors & carriers for atoms or functional groups that are removed from substrate

17. 5) Molecules interacting with enzyme: Allosteric Modulators bind to enzyme away from active site changing shape of active site for better or for worse Allosteric Activator Fig 2-20 Allosteric Inhibitor

18. 5) Molecules interacting with enzyme cont. Competitive inhibitors: reversible binding to active site Fig 2-19 block active site • Also possible: irreversible binding via covalent bonds, e.g.: • Penicillin • Cyanide

19. Reversible Reactions follow the Law of Mass Action Fig 4-9

20. Three Major Types of Enzymatic Reactions: • Oxydation - Reduction reactions (transfer of ?) • Hydrolysis - Dehydration reactions (breakdown & synthesis of ?) • Addition-Subtraction-Exchange reactions

22. ?

23. Metabolism Anabolism Catabolism  

24. Metabolism definition: ___________ Metabolic pathways = network of linked reactions Cells regulate metabolic pathways via • Control of enzyme concentration • Modulator production (allosteric modulators, feedback inhibition, Fig 4-11) • Different enzymes for reversible rxs, Fig 4-12) • Compartmentation of enzymes • ATP / ADP ratio

25. Metabolic pathways: Network of interconnected chemical reactions Linear pathway Intermediates Circular pathway Branched pathway

26. Special case: = end product inhibition Fig 4-11

28. Catabolic Pathways: ATP-Production Amount of ATP produced reflects on usefulness of metabolic pathways: Aerobic pathways Anaerobic pathways Different biomolecules enter pathway at different points

29. ATP Cycle ATP = Energy Carrier of Cell (not very useful for energy storage) ATP : ADP ratio determines status of ATP synthesis reactions

30. Glycolysis • From 1 glucose to 2 pyruvate molecules • Main catabolic pathway of cytoplasm • Does not require O2  part of _________ and ____________ catabolism • Starts with phosphorylation (“Before doubling your money you first have to invest!”) Fig 4-13

31. Pyruvate has 2 Possible Fates Anaerobic catabolism:Pyruvate lactate Aerobic catabolism:Pyruvate Citric Acid Cycle

32. Citric Acid Cycle Other names ? Takes place in ? Energy Produced: 1 ATP 3 NADH 1 FADH2 Waste – 2 CO2 Fig. 4-16

33. NADH NADH NADH FADH2 Energy Yield of Krebs Cycle Compare to Fig. 4-16

34. Final step:Electron Transport System • Chemiosmotic theory / oxydative phosphorylation • Transfers energy from NADH and FADH2 to ATP (via e- donation and H+ transport) • Mechanism:Energy released by movement of e- trough transport system is stored temporarily in H+ gradient • NADH produces a maximum of 2.5 ATP FADH2 produces a maximum of 1.5 ATP • 1 ATP formed per 3H+ shuttled through ATP Synthase Fig 4-17

35. Cellular Respiration Maximum potential yield for aerobic glucose metabolism: 30-32 ATP synthesized from ADP H2O is a byproduct

36. Synthetic Pathways Anabolic rxs synthesize large biomolecules Unit molecules Macromolecules nutrients & energy required Polysaccharides Lipids DNA Protein

37. Glycogen Synthesis Gluconeogenesis Made from glucose Stored in all cells but especially in • Liver (keeps 4h glycogen reserve for between meals) • Skeletal Muscle  muscle contraction Glycolysis in reverse From glycerol, aa and lactate All cells can make G-6-P, only liver and Kidney can make glucose

38. Protein Synthesis Proteins are the key to cell function → necessary for all cell functions Protein synthesis is under nuclear direction  DNA specifies Proteins DNA mRNA Protein ? ?

39. How can only 4 bases in DNA encode > 20 different aa in protein? 1 letter word: 1 base = 1 aa how many possibilities? 2 letter word: 2 bases = 1 aahow many possibilities? 3 letter word: 3 bases = 1 aa how many possibilities? 3 letter words = base triplets or codons

40. 1 start codon (AUG = Met) 3 stop codons 60 other codons for 19 aa Redundancy of Genetic Code

41. Transcription DNA is transcribed into complementary mRNA by RNA Polymerase + nucleotides + Mg2+ ( = ?) + ? Gene = elementary unit of inheritance Compare to Fig. 4-25 and review Fig 4-26

42. Translation mRNA is translated into string of aa (= polypeptide) 2 important components ?? mRNA + ribosomes + tRNA meet in cytoplasm Anticodon pairs with mRNA codon  aa determined Amino acids are linked via ______________ bond. Fig 4-27

43. Post – Translational protein modifications: Folding, cleavage, additions  glyco- , lipo- proteins Protein Sorting Due to signal/targeting sequence • No targeting sequence protein stays in cytoplasm • Targeting sequence protein destined for translocation into organelles or for export from cell

44. For “export proteins”: Signal sequence leads growing polypeptide chain across ER membrane into ER lumen Modifications in ER Transition vesicles to Golgi apparatus for further modifications Transport vesicles to cell membrane Compare to Fig 4-28

45. DNA Replication • Semi- conservative • DNA polymerase

46. the end Running problem: Tay-Sachs Disease