Cellular Metabolism

1. Cellular Metabolism Chapter 4

2. Cellular Metabolism • Cellular metabolism refers to all of the chemical processes that occur inside living cells.

3. Energy • Energy can exist in two states: • Kinetic energy – energy of motion. • Potential energy – stored energy. • Chemical energy – potential energy stored in bonds, released when bonds are broken. • Energy can be transformed form one state to another.

4. Energy • The ultimate source of energy for most living things is the sun.

5. Laws of Thermodynamics • First law of thermodynamics – energy cannot be created or destroyed – only transformed. • Second law of thermodynamics – a closed system moves toward entropy, increasing disorder. • Living systems are open systems that maintain organization and increase it during development.

6. Free Energy • Free energy – the energy available for doing work. • Most chemical reactions release free energy – they are exergonic. • Downhill • Some reactions require the input of free energy – they are endergonic. • Uphill

7. Enzymes • Bonds must be destabilized before any reaction can occur – even exergonic. • Activation energy must be supplied so that the bond will break. • Heat – increases rate at which molecules collide. • Catalysts can lower activation energy.

8. Enzymes • Catalysts are chemical substances that speed up a reaction without affecting the products. • Catalysts are not used up or changed in any way during the reaction. • Enzymes are important catalysts in living organisms.

9. Enzymes • Enzymes reduce the amount of activation energy required for a reaction to proceed. • Enzymes are not used up or altered. • Products are not altered. • Energy released is the same.

10. Enzymes • Enzymes may be pure proteins or proteins plus cofactors such as metallic ions or coenzymes, organic group that contain groups derived from vitamins.

11. Enzyme Function • An enzyme works by binding with its substrate, the molecule whose reaction is catalyzed. • The active site is the location on the enzyme where the substrate fits. • Enzyme + Substrate = ES complex.

12. Enzyme Specificity • Enzymes are highly specific. • There is an exact molecular fit between enzyme and substrate. • Some enzymes work with only one substrate, others work with a group of molecules. • Succinic dehydrogenase oxidizes only succinic acid. • Proteases will act on any protein, although they still have a specific point of attack.

13. Enzyme-Catalyzed Reactions • Enzyme-catalyzed reactions are reversible. • Indicated by double arrows in reactions. • Tend to go mostly in one direction. • Reactions tend to be catalyzed by different enzymes for each direction. • Catabolic (degradation) reaction catalyzed by enzyme A. • Anabolic (synthesis) reaction catalyzed by enzyme B.

14. Importance of ATP • Endergonic reactions require energy to proceed. • Coupling an energy-requiring reaction with an energy-yielding reaction can drive endergonic reactions. • ATP is the most common intermediate in coupled reactions.

15. Importance of ATP • ATP consists of adenosine (adenine + ribose) and a triphosphate group. • The bonds between the phosphate groups are high energy bonds. • A-P~P~P

16. Importance of ATP • Phosphates have negative charges. • Takes lots of energy to hold 3 in a row! • Ready to spring apart. • So, ATP is very reactive.

17. Importance of ATP • A coupled reaction is a system of two reactions linked by an energy shuttle – ATP. • Substrate B is a fuel – like glucose or lipid. • ATP is not a storehouse of energy – used as soon as it’s available.

18. Oxidation – Reduction - Redox • An atom that loses an electron has been oxidized. Oxygen is a common electron acceptor. • An atom that gains an electron has been reduced. Higher energy.

19. Redox Reactions • Redox reactions always occur in pairs. • One atom loses the electron, the other gains the electron. • Energy is transferred from one atom to another via redox reactions.

20. Cellular Respiration • Cellular respiration – the oxidation of food molecules to obtain energy. • Electrons are stripped away. • Different from breathing (respiration).

21. Cellular Respiration • Aerobic versus Anaerobic Metabolism • Heterotrophs • Aerobes: Use molecular oxygen as the final electron acceptor • Anaerobes: Use other molecules as final electron acceptor • Energy yield much lower ATP yield

22. Cellular Respiration • When oxygen acts as the final electron acceptor (aerobes): • Almost 20 times more energy is released than if another acceptor is used (anaerobes). • Advantage of aerobic metabolism: • Smaller quantity of food required to maintain given rate of metabolism.

23. Aerobic Respiration • In aerobic respiration, ATP forms as electrons are harvested, transferred along the electron transport chain and eventually donated to O2 gas. • Oxygen is required! • Glucose is completely oxidized. • C6H12O6 + 6O2 6CO2 + 6H2O + energy (heat Glucose Oxygen Carbon Water or ATP) Dioxide

24. Cellular Respiration - 3 Stages • Food is digested to break it into smaller pieces – no energy production here. • Glycolysis – coupled reactions used to make ATP. • Occurs in cytoplasm • Doesn’t require O2 • Oxidation – harvests electrons and uses their energy to power ATP production. • Only in mitochondria • More powerful

25. Anaerobic Respiration • Anaerobic respiration occurs in the absence of oxygen. • Different electron acceptors are used instead of oxygen (sulfur, or nitrate). • Sugars are not completely oxidized, so it doesn’t generate as much ATP.

26. Glycolysis • Glycolysis – the first stage in cellular respiration. • A series of enzyme catalyzed reactions. • Glucose converted to pyruvic acid. • Small number of ATPs made (2 per glucose molecule), but it is possible in the absence of oxygen. • All living organisms use glycolysis.

27. Glycolysis • Uphill portion primes the fuel with phosphates. • Uses 2 ATPs • Fuel is cleaved into 3-C sugars which undergo oxidation. • NAD+ accepts e-s & 1 H+ to produce NADH • NADH serves as a carrier to move high energy e-s to the final electron transport chain. • Downhill portion produces 2 ATPs per 3-C sugar (4 total). • Net production of 2 ATPs per glucose molecule.

28. Glycolysis • Summary of the enzymatically catalyzed reactions in glycolysis: Glucose + 2ADP + 2Pi + 2 NAD+ 2 Pyruvic acid + 2 NADH + 2ATP http://www.youtube.com/watch?v=3GTjQTqUuOw&list=FL9N_Px072WuVorSwDfqf-9w&index=4&feature=plpp

29. Harvesting Electrons form Chemical Bonds • When oxygen is available, a second oxidative stage of cellular respiration takes place. • First step – oxidize the 3-carbon pyruvate in the mitochondria forming Acetyl-CoA. • Next, Acetyl-CoA is oxidized in the Krebs cycle.

30. Producing Acetyl-CoA • The 3-carbon pyruvate loses a carbon producing an acetyl group. • Electrons are transferred to NAD+ forming NADH. • The acetyl group combines with CoA forming Acetyl-CoA. • Ready for use in Krebs cycle.

31. The Krebs Cycle • The Krebs cycle is the next stage in oxidative respiration and takes place in the mitochondria. • Acetyl-CoA joins cycle, binding to a 4-carbon molecule to form a 6-carbon molecule. • 2 carbons removed as CO2, their electrons donated to NAD+, 4-carbon molecules left. • 2 NADH produced. • More electrons are extracted and the original 4-carbon material is regenerated. • 1 ATP, 1 NADH, and 1 FADH2 produced.

33. The Krebs Cycle • Each glucose provides 2 pyruvates, therefore 2 turns of the Krebs cycle. • Glucose is completely consumed during cellular respiration.

34. The Krebs Cycle Acetyl unit + 3 NAD+ + FAD + ADP + Pi 2 CO2 + 3 NADH + FADH2 + ATP http://www.youtube.com/watch?v=-cDFYXc9Wko

35. Using Electrons to Make ATP • NADH & FADH2 contain energized electrons. • NADH molecules carry their electrons to the inner mitochondrial membrane where they transfer electrons to a series of membrane bound proteins – the electron transport chain.

36. Building an Electrochemical Gradient • In eukaryotes, aerobic metabolism takes place in the mitochondria in virtually all cells. • The Krebs cycle occurs in the matrix, or internal compartment of the mitochondrion. • Protons (H+) are pumped out of the matrix into the intermembrane space.

37. Producing ATP- Chemiosmosis • A strong gradient with many protons outside the matrix and few inside is set up. • Protons are driven back into the matrix. • They must pass through special channels that will drive synthesis of ATP. • Oxidative phosphorylation

39. Electron Transport Review http://www.youtube.com/watch?v=kN5MtqAB_Yc&list=FL9N_Px072WuVorSwDfqf-9w&index=2&feature=plpp

40. Review of Cellular Respiration • 1 ATP generated for each proton pump activated by the electron transport chain. • NADH activates 3 pumps. • FADH2 activates 2 pumps. • The 2 NADH produced during glycolysis must be transported across the mitochondrial membrane using 2 ATP. • Net ATP production = 4

41. Glucose + 2 ATP + 36 ADP + 36 Pi + 6 O2 6CO2 + 2 ADP + 36 ATP + 6 H2O

42. Fermentation • In the absence of oxygen, the end-product of glycolysis, pyruvate, is used in fermentation. • During glycolysis, all the NAD+ becomes saturated with electrons (NADH). When this happens, glycolysis will stop. • 2 NADH and 2 ATP produced. • Pyruvate is used as the electron acceptor resetting the NAD+ for use in glycolysis.

43. Fermentation – 2 Types • Animals add extracted electrons to pyruvate forming lactate. • Reversible when oxygen becomes available. • Muscle fatigue • Yeasts, single-celled fungi, produce ethanol. • Present in wine & beer. • Alcoholic fermentation

45. Metabolism of Lipids • Triglycerides are broken down into glycerol and 3 fatty acid chains. • Glycerol enters glycolysis. • Fatty acids are oxidized and 2-C molecules break off as acetyl-CoA. • Oxidation of one 18-C stearic acid will net 146 ATP. • Oxidation of three glucose (18 Cs) nets 108 ATP. • Glycerol nets 22 ATP, so 1 triglyceride nets 462 ATP.

46. Metabolism of Proteins • Proteins digested in the gut into amino acids which are then absorbed into blood and extracellular fluid. • Excess proteins can serve as fuel like carbohydrates and fats. • Nitrogen is removed producing carbon skeletons and ammonia. • Carbon skeletons oxidized.

47. Metabolism of Proteins • Ammonia is highly toxic, but soluble. • Can be excreted by aquatic organisms as ammonia. • Terrestrial organisms must detoxify it first.

48. Regulating Cellular Respiration • Rate of cellular respiration slows down when your cells have enough ATP. • Enzymes that are important early in the process have an allosteric (regulating) site that will bind to ATP. • When lots of ATP is present, it will bind to this site, changing the shape of the enzyme, halting cellular respiration.

49. Regulating Cellular Respiration • Enzyme activity is controlled by presence or absence of metabolites that cause conformational changes in enzymes. • Improves or decreases effectiveness as catalyst.