Cellular Metabolism/Enzymes
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1. Cellular Metabolism and Enzymes 2-7. Enzymes Biological catalysts Increase rate of chemical reactions Proteins Lower activation energy Energy required for a reaction to proceed __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ Structure determines function Conformation Highly-ordered 3-dimensional shape Active sites “Pockets” into which substrates fit Bring substrates close together so reaction can occur __________________________________________ Steps Substrates fit into active sites Enzyme-substrate complex formed Reaction occurs Products dissociate Enzyme is unaltered Enzyme is reused __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ http://phschool.com/science/biology_place/labb ench/lab2/active.html __________________________________________ 8. Substrate Specificity __________________________________________ http://phschool.com/science/biology_place/labb ench/lab2/binding.html __________________________________________ 9. Induced Fit __________________________________________ http://phschool.com/science/biology_place/labb ench/lab2/induced.html 10-14. Naming Conventions End in “-ase” Activity Phosphatases remove phosphate groups Kinases add phosphate groups (phosphorylate) Substrate Lactase Substrate and activity Lactate dehydrogenase Hydrolase Phosphatase Synthase/synthetase Dehydrogenase Kinase Isomerase - __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ 15. Isoenzymes Different models of the same enzyme Produced by different organs CPK MM BB MB __________________________________________ 16. Enzyme Activity Measured by rate at which substrates are converted to products Affected by Temperature pH Concentrations Enyzmes Substrates Coenzymes Cofactors __________________________________________ 17. Enzyme Activity – Temperature Enzymes have optimal temperature range Typically near normal physiological values __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ 18. Enzyme Activity – pH Enzymes have optimal pH range Usually reflects pH of body fluid 19. Effects of pH http://phschool.com/science/biology_place/labbench/l ab2/ph.html __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ 20-22. Cofactors / Coenzymes http://upload.wikimedia.org/wikibooks/en/a/a 8/Metal_ion.GIF __________________________________________ __________________________________________ __________________________________________ Necessary for normal enzyme activity Cofactors metal ions Ca+2, Mg+2, Mn+2, Cu+2, Zn+2 and selenium Coenzymes derived from vitamins transport small molecules needed by enzymes __________________________________________ Cofactor binding changes conformation of active site and aids in temporary bonding between enzyme and substrates __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ http://www.elmhurst.edu/~chm/vchembook/571cofa ctor.html __________________________________________ __________________________________________ __________________________________________ http://academic.brooklyn.cuny.edu/biology/bio4fv/p age/coenzy_.htm __________________________________________ 23. Enzyme Activation Produced in an inactive form Pancreatic digestive enzymes Protects against self-digestion Phosphorylation - activation / Dephosphorylation - inactivation Others activated by ligands (small molecules) called 2nd messengers Often cyclic AMP (cAMP) __________________________________________ 24. Effect of Substrate Concentration Rate of reaction increases as substrate concentration increases Plateau Maximum velocity Saturation of enzyme 25. Reversible Reactions Some enzymatic reactions are reversible Both forward and backward reactions are catalyzed by same enzyme Law of mass action direction of reaction is from side of equation where concentration is higher to side where concentration is lower E.g. carbonic anhydrase catalyzes » H2O + CO2 H2CO3 __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ 26. Metabolism Definition Anabolism Catabolism __________________________________________ 27. Metabolic Pathways __________________________________________ 28. End-Product Inhibition __________________________________________ __________________________________________ __________________________________________ __________________________________________ 29. Inborn Errors of Metabolism __________________________________________ Are due to inherited defects in genes for enzymes in metabolic pathways Metabolic disease can result from either: Increases in intermediates formed prior to the defective enzyme Or decreases in products normally formed after the defective enzyme __________________________________________ 30. Bioenergetics Flow of energy in living systems __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ Laws of thermodynamics 1st law Law of conservation of energy Energy can be changed from one form to another, but it cannot be created or destroyed. 31. Endergonic vs. Exergonic Endergonic reactions Require input of energy to proceed Products contain more free energy than reactants Exergonic reactions Release energy as they proceed Products contain less free energy than reactants 32. Endergonic/Exergonic Reactions 33. Coupled Reactions Couple endergonic reactions to exergonic reactions 34. ATP 35. Oxidation-Reduction Reduction molecule gains electrons Reducing agents donate electrons Oxidation Molecule loses electrons Oxidizing agents accept electrons Reduction and oxidation (Redox) coupled reactions Often involve transfer of hydrogens instead of electrons NAD and FAD Coenzymes that play important roles as H carriers 36. Generation of ATP Source = Chemical energy stored in carbon bonds of ingested food Must be converted to high energy phosphate bonds of ATP ATP ADP + Pi + energy for cellular use 37-41. Glycolysis Breakdown of glucose Occurs in cytoplasm Yield = 2 molecules of ATP and 2 molecules of pyruvic acid Does not require oxygen Metabolic pathway ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ ___________________________ Glucose + 2NAD + 2ADP + 2Pi 2 pyruvates + 2NADH + 2 ATP Glucose must be activated with 2ATPs Phosphorylation traps glucose inside cell Exergonic – – net of 2ATPs and 2NADHs 2ATPs added 4ATPs produced __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ 42-43. Lactic Acid Pathway In absence of O2 NADH gives its Hs to pyruvate lactic acid created anaerobic respiration or fermentation Only yields a net gain of 2 ATPs per glucose RBCs No mitochondria Use only lactic acid pathway Don’t use O2 that they are carrying Skeletal and cardiac muscle Conditions of low O2 Exercise or insufficient blood supply __________________________________________ 44. Citric Acid Cycle or Kreb’s Cycle Pyruvic acid from glycolysis mitochondrial matrix Yield = 3CO2, 4NADH, 1FADH2, 1ATP per pyruvic acid Glycolysis + Citric Acid Cycle yields a total of 4ATP per molecule of glucose NADH and FADH2 carry electrons to Electron Transport Chain (ETC) 45. http://homepages.ius.edu/GKIRCHNE/Glycolysis.htm __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ 46-47. Electron Transport Chain Occurs at inner membrane of mitochondrion Electron carrier molecules extract electrons from the hydrogens in NADH and FADH2 As electrons move through progressively lower energy levels, energy is released 32 molecules of ATP per glucose molecule Electrons eventually pass to oxygen, oxygen combines with hydrogen to form H2O Oxidative phosphorylation As each protein in ETC accepts electrons it is reduced When it gives electrons to next protein it is oxidized This process is exergonic Energy is used to phosphorylate ADP to make ATP Oxidative phosphorylation __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ 48. Function of Oxygen O2 is the final electron acceptor Combines with 4H+s O2 + 4 e- + 4 H+ 2 H20 49. ATP Formation Direct (substrate-level) phosphorylation ATP is generated when bonds break Glycolysis (2ATP) Kreb’s cycle (2ATP) Oxidative phosphorylation Where ATP generated by ETC 30-32 ATPs 50-52. Aerobic vs. Anaerobic O2 Glucose Pyruvic acid Pyruvic acid Citric acid cycle Electron transport chain Net yield = ~36 ATP No O2 Glucose Pyruvic acid Net yield = 2ATP __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ Lactic acid __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________ __________________________________________
