Cell Metabolism

1. Metabolism Cell Metabolism

2. Energy • Energy is the capacity to do work. A handful of peanuts contains enough energy to boil a quart of water

3. Energy Forms • Forms of energy: • Potential energy • Kinetic energy Conversion of potential energy to kinetic energy High potential energy Low potential energy Conversion of kinetic energy to potential energy

4. Cellular Work • Cells use energy for: • Mechanical work • Transport work • Chemical work • Cellular Work • = Metabolism It takes about 10 million ATP molecules per second to power an active muscle cell.

5. First Law of Thermodynamics • The total amount of energy in the universe remains constant. • Energy can be transformed from one form to another, but it cannot be created or destroyed.

6. Second Law of Thermodynamics Energy transformations increase entropy (degree of disorder) in a closed system. • No energy conversion is 100 percent efficient. Systems tend to go from states of higher free energy to states of lower free energy.

7. Exergonic Reactions EnergyReleased High EnergyReactants A + B Low EnergyProducts Energy is released. Products have less energy than starting substance. + C D

8. Exergonic Example CH2OH O O OH O O H H O O C O EnergyReleased + High EnergyReactants + Low EnergyProducts

9. Exergonic Energy Diagram high Energycontentofmolecules low Progress of reaction An exergonic reaction: Burning Glucose Activation energy neededto start reaction Glucose + O2 Energy released byburning glucose C O2 + H2O

10. Endergonic Reactions A B + C D + energy Energy input is required Products store more energy than starting substances. High EnergyProducts Low EnergyReactants

11. Endergonic Energy Diagram high Energycontentofmolecules low Progress of reaction (b) An endergonic reaction: Photosynthesis Glucose Net energyincrease bysynthesizingglucose Activationenergy fromlight storedby photosynthesis CO2 + H2O

12. Endergonic Example CH2OH EnergySupplied O O OH + O O H H High EnergyProducts O O C O Low EnergyReactants +

13. Energy Flow • Energy flows into ecosystems as sunlight. (The sun is life’s primary energy source.) • Producers (autotrophs) trap energy from the sun and convert it into chemical bond energy. • All organisms use the energy stored in the bonds of organic compounds to do work. • LIVING SYSTEMS ARE NOT CLOSED SYSTEMS!

14. Energy Relationships Chemical reactions either store or release energy. large energy-rich molecules (fats, complex carbohydrates, proteins, nucleic acids) ADP + Pi BIOSYNTHETIC PATHWAYS (ANABOLIC) DEGRADATIVE PATHWAYS (CATABOLIC) simple organic compounds (simple sugars, amino acids, fatty acids, nucleotides) ATP energy-poor products (such as carbon dioxide, water) ENERGY INPUT

15. The Role of ATP • Cells “earn” ATP in exergonic reactions. • Cells “spend” ATP in endergonic reactions. adenine P P P ribose ATP - adenosine triphosphate

16. ADP & ATP NH2 NH2 OH OH C C N N C C N N HC HC Adenine Adenine ~ CH CH C C O P O P OH N N N N O O OH H2C H2C Ribose Ribose O O H H H H H H H H P OH OH OH OH OH O OH OH ~ O P O P O O O DiPhosphate ADP High-energyPhosphateBond TriPhosphate ~ ATP

17. Coupled Reactions: Synthesis

18. Coupled Reaction: Phosphorylation

19. Coupled Reactions: Muscle Action

20. Active Transport High solute concentration Low solute concentration • ATP gives up phosphate to activate protein. • Binding of ATP changes protein shape and affinity for solute. P ATP ADP P P P

21. Electron Carriers

22. Enzyme Action • Enzymes speed up metabolic reactions by lowering activation energy. • Enzymes are substrate specific. • Enzyme activity is regulated by inhibitors. • A cell’s physical and chemical environment effects enzyme activity.

23. Hydrolysis of Sucrose

24. Enzymes are Catalyst • Enzymes speed up metabolic • reactions by lowering activation energy • A catalyst is a chemical agent that changes the rate of a reaction without being consumed by the reaction. • An enzyme is a catalytic protein. • Enzymes regulate the movement of molecules through metabolic pathways.

25. A B 298oK, no catalyst T, no catalyst high 298oK, inorganic catalyst A + B 298oK, enzyme Energycontentofmolecules C + D low Progress of reaction “Lowering” Activation Energy Fig. 2

26. Metabolic Pathways D E InitialReactants Intermediates FinalProducts B C A Enzyme 1 Enzyme 2 Enzyme 3 Enzyme 4 Pathway 1 F G Pathway 2 Enzyme 5 Enzyme 6

27. Enzymes Specificity • b. Enzymes are substrate specific • A substrate is a reactant which binds to an enzyme. • When a substrate or substrates binds to an enzyme, the enzyme catalyzes the conversion of the substrate to the product.

28. Enzyme Active Sites • The active site of an enzyme is a pocket or groove on the surface of the protein. • • The specificity of an enzyme is due to the fit between the active site and the substrate. • • As the substrate binds, the enzyme changes shape leading to a tighter induced fit.

29. products induction of fit enzyme-substrate (ES) complex initial binding due to e.g., charge interactions enzyme ES* ES E + P Induced Fit Model substrate Fig. 3 enzyme E + S enzyme unchanged by reaction TRANSITION STATE good orientation but unstable substrate contact with active site

30. Enzyme-Substrate Interactions Substrate Substrate 1 Substrates enter active site ActiveSite 2 Shape change promotes reaction Enzyme Product released;enzyme ready again

31. c. Enzyme activity is regulated by inhibitors. • Some molecules inhibit enzymes from catalyzing reactions. • If the inhibitor binds to the same site as the substrate, then it blocks substrate binding via competitive inhibition. • If the inhibitor binds somewhere other than the active site, it blocks substrate binding via noncompetitive inhibition.

32. Negative Feedback Models

33. End Product Inhibition • Prevents excess accumulation of final product. • Results in alternative pathway and product.

34. Feedback Inhibition CH3 CH3 CH2 OH H C CH3 H C NH3 H C NH3 H C COOH COOH Feedback InhibitionIsoleucine inhibits enzyme 1 A B C D E 1 E 2 E 3 E 4 E 5 Threonine(substrate) Isoleucine(end product)

35. Allosteric Regulation vs. Competition Shape of activesite changed Substrate (a) (b) Active Site Enzyme Allosteric Regulatory Molecule Competitive inhibitoroccupies active site Allosteric Site (c)

36. Effects on Enzyme Action • d. A cell’s physical and chemical • environment effects enzyme activity • The three-dimensional structure of enzymes depend on environmental conditions. • Changes in shape influence the reaction rate. • Some conditions lead to the most active conformation and optimal rate of reaction.

37. Effect of pH • pH influences shape and reaction rate. • Each enzyme has an optimal pH (usually between pH 6 – 8). • However, digestive enzymes in the stomach are designed to work best at pH 2 while those in the intestine are optimal at pH 9.

38. Effect of Temperature • As temperature increases, collisions between substrates and active sites occur more frequently. • • At some point, thermal agitation begins to destabilize the protein’s active conformation and the protein denatures. • • Each enzyme has an optimal temperature.

39. Effect of Cofactors & Coenzymes • Many enzymes require nonprotein cofactors for catalytic activity and include zinc, iron, and copper. • • Organic cofactors, coenzymes, include vitamins or molecules derived from vitamins.

40. Effect of Substrate Concentration • The rate of product formation increases as the [substrate] increases. • Rate levels when enzyme becomes saturated. • Additional substrate does not not increase reaction rate.

41. Metabolism The end