METABOLISM

1. METABOLISM FUELING CELL GROWTH

2. METABOLISM Metabolism encompasses two general processes Catabolism Processes harvesting energy released during the breakdown of various compounds Harvested energy generally used to synthesize ATP Anabolism a.k.a., �Biosynthesis� Processes using stored energy to synthesize and assemble subunits of macromolecules Catabolism is coupled to anabolism

3. METABOLIC PATHWAYS Ordered sequence of steps resulting in an end-product Reactants ? intermediate 1 ? � ? end product Pathway may be linear, branched, or cyclic Each reaction typically catalyzed by a specific enzyme

4. NEED FOR ENERGY The environment within a cell is highly organized and separate from the external environment Maintaining this ordered environment costs energy Many processes within a cell require energy The requirement for energy is a unifying feature of life Many organisms extract energy from food via aerobic cellular respiration

5. HARVESTING ENERGY Your car harvests energy from food (gasoline) Your furnace harvests energy from food (methane) Your cells harvest energy from food In each of these cases, O2 is required Food + O2 ? energy + CO2 + H2O

6. HARVESTING ENERGY Methane and glucose possess a large amount of energy in their chemical bonds Reduced forms of carbon CO2 possesses little useful energy in its chemical bonds Oxidized form of carbon Energy is released when reduced molecules are burned (oxidized) Converted from a reduced form to a more oxidized form

7. OXIDATION & REDUCTION Oxidation is required to harvest large amounts of energy from glucose (or methane, gasoline, etc.) Oxidation involves the loss of electrons Whenever one molecule is oxidized, another is reduced e.g., O2 is reduced to H2O (�O2 + 2H+ + 2e- ? H2O) e.g., NAD+ is reduced to NADH (NAD+ + H+ + 2e- ? NADH)

8. HARVESTING ENERGY Your car, your furnace, and your cells burn (oxidize) food to release energy Much of this energy is converted into a useful form Your car transforms much of this energy into movement Your furnace transforms much of this energy into heat Your cells transform much of this energy into ATP Food + O2 ? energy + CO2 + H2O

9. ATP The oxidation of food molecules converts harvested energy to ATP (adenosine triphosphate) High energy molecule Energy currency of cell �Spent� (hydrolyzed into ADP) to fuel many processes

10. ATP CYCLE ATP and ADP are readily interconverted ATP ? ADP releases energy ADP ? ATP requires energy

11. ATP CYCLE Energy-releasing reactions store energy as ATP ADP ? ATP Energy-requiring reactions receive energy from ATP ATP ? ADP

12. NADH The reduced coenzyme NADH is also produced during cellular respiration Nicotinamide adenine dinucleotide High energy molecule Can be �spent� to make more ATP later

13. NADH NAD+ and NADH are readily interconverted NAD+ + H+ + 2e- ? NADH As glucose is oxidized, NAD+ is reduced to NADH

14. STAGES OF RESPIRATION Aerobic cellular respiration can be divided into three main stages: Glycolysis Krebs Cycle Electron Transport Pathway

15. GLYCOLYSIS Occurs within eukaryotic cytoplasm Multi-step metabolic pathway Partial oxidation of glucose Products: 2 ATP 2 NADH 2 pyruvate

16. ALTERNATE PATHWAYS Other ways to convert glucose to pyruvate Entner-Doudoroff Pathway Utilized by some bacteria & archaea Instead of or in addition to glycolysis Uses different enzymes Generates reducing power as NADPH Yields slightly less ATP Pentose Phosphate Pathway Operates in conjunction with other glucose-degrading pathways Primary role is production of compounds used in biosynthesis Generates reducing power as NADPH Can produce a single pyruvate molecule

17. ALTERNATE PATHWAYS The pentose phosphate pathway removes carbons from glucose one at a time C6 ? C5 ? C4 ? C3 (pyruvate) The pentose sugar (C5) is of particular importance as a precursor metabolite What critically important biomolecule do you think is generally made from this pentose sugar?

18. TRANSITION STEP The pyruvate produced in glycolysis (etc.) Enters the mitochondria Is converted into acetyl CoA Enters the Krebs Cycle

19. KREBS CYCLE Occurs within mitochondrial matrix Multi-step metabolic pathway Remnants of glucose completely oxidized Products: 2 ATP 6 NADH 2 FADH2 4 CO2

20. GLYCOLYSIS ? KREBS Several high-energy molecules are produced during glycolysis and the Krebs cycle 4 ATP 10 NADH 2 FADH2 Most of the energy harvested from glucose is in the form of reduced coenzymes However, only ATP is readily usable to perform cellular work The Electron Transport Pathway oxidizes NADH and FADH2 to produce more ATP

21. ELECTRON TRANSPORT PATHWAY Occurs within the inner mitochondrial membrane Electrons are removed from NADH and shuttled through a series of electron acceptors Energy is removed from the electrons with each transfer This energy is used to make ATP NADH ? 3 ATP FADH2 ? 2 ATP O2 is the terminal electron acceptor �O2 + 2H+ + 2e- ? H2O Anaerobic respiration utilizes a molecule other than O2 as the terminal electron acceptor e.g., NO3-, SO42-, CO2, etc.

22. CHEMIOSMOSIS As electrons are shuttled from one acceptor to the next, protons are transported across the membrane Electrochemical (proton) gradient produced Protons re-enter the matrix via a proton channel associated with an ATP synthase complex As protons move down their concentration gradient, ATP is produced

23. PROKARYOTES Do prokaryotes have energy needs? Do some of them perform aerobic respiration, even though they have no mitochondria? How?

24. ENERGY YIELD 4 ATP 10 NADH ? 30 ATP 2 FADH2 ? 4 ATP 38 ATP total

25. THEORETICAL YIELD Theoretical yield of 38 ATP not generally reached because: Intermediates in central pathways siphoned off as precursor metabolites for biosynthesis Electrons of NADH generated in cytosol often shuttled into mitochondria as FADH Each NADH typically yields slightly less than 3 ATP

26. BURNING OTHER STUFF Glucose can be oxidized to yield ATP Other biomolecules can also be oxidized to yield ATP These molecules are converted to either glucose or to an intermediate in the catabolism of glucose

27. O2 REQUIREMENT ~38 ATP produced per glucose molecule 4 ATP from substrate level phosphorylation 34 ATP from oxidative phosphorylation Produced via ETP Requires adequate supply of oxygen Under conditions of insufficient oxygen, ATP yields can be severely reduced

28. What happens when O2 is unavailable? Some cells cannot obtain energy when deprived of O2 e.g., human heart cells �Obligate aerobes� Some cells normally perform aerobic respiration, but can still obtain energy when O2 is lacking e.g., skeletal muscle cells, S. cerevisiae (yeast), E. coli �Facultative anaerobes� Others do not use O2 to obtain energy e.g., Clostridium botulinum, an �obligate anaerobe� e.g., Streptococcus pyogenes, an �aerotolerant anaerobe�

29. FACULTATIVE ANAEROBES In the absence of O2, aerobic respiration is impossible O2 is the terminal electron acceptor of the ETP Without O2, the ETP does not function The Krebs Cycle produces mainly NADH Without O2, NADH is useless Without O2, the Krebs Cycle does not function * Some anaerobes normally undergo �anaerobic respiration,� where a molecule other than O2 serves as the terminal electron acceptor. For these organisms, the Krebs Cycle and ETP continue to function in the absence of O2.

30. FACULTATIVE ANAEROBES In the absence of O2, aerobic respiration is impossible Glycolysis still occurs Net ATP production: 2 ATP 2 is significantly less than thirty-something NAD+ is converted to NADH NADH is not useful to the cell The absence of NAD+ is detrimental to the cell NADH must be converted back to NAD+ �Fermentation�

31. FERMENTATION NADH is produced during glycolysis Energy in NADH cannot be used NADH must be oxidized to replenish NAD+ No payoff NADH is oxidized to NAD+ Pyruvate is reduced to _______ (Different substances in different organisms) Human muscle: pyruvate ? lactic acid Yeast: pyruvate ? ethanol & CO2 Other cells ? many other molecules Total energy yield of fermentation is the 2 ATP generated in glycolysis

32. FERMENTATION Skeletal muscles normally undergo aerobic respiration During strenuous exercise, O2 may be rapidly depleted Fermentation can continue to provide energy Pyruvate ? lactic acid Lactic acid builds up Buildup causes muscle fatigue & pain Lactic acid ultimately removed

33. FERMENTATION Saccharomyces cerevisiae (yeast) normally undergoes aerobic respiration O2 is not always available Fermentation can continue to provide energy Pyruvate ? ethanol & CO2 Ethanol ultimately toxic

34. FERMENTATION Many other organisms also undergo fermentation Some are facultative anaerobes Some are obligate fermenters Pyruvate is converted into a host of different molecules by a host of different organisms Many of these molecules are commercially important

35. HOW MUCH ENERGY? Aerobic and anaerobic respiration are both reasonably efficient Fermentation is far less efficient

36. PHOTOSYNTHESIS Cellular respiration involves the oxidation of glucose and other high-energy (reduced) molecules These molecules are ultimately produced by photosynthesis Photosynthesis nourishes virtually the entire world, either directly or indirectly

37. PHOTOSYNTHESIS Who does photosynthesis? Though plants can photosynthesize, microorganisms are responsible for the majority of the photosynthesis occurring on the planet

38. CHLOROPLASTS Chloroplasts are the site of photosynthesis Remember, photosynthetic bacteria don�t have chloroplasts, they essentially are chloroplasts Chloroplasts contain the pigment chlorophyll Pigments absorb light Multiple similar forms of chlorophyll exist The light absorbed is ultimately used to reduce CO2 to glucose

39. PHOTOSYNTHESIS Plants can perform photosynthesis Can plants perform aerobic cellular respiration?

40. PHOTOSYNTHESIS Photosynthesis consists of two processes Light reactions a.k.a., Light-dependent reactions Dark reactions a.k.a., Light-independent reactions a.k.a., Calvin cycle Both the light reactions and the dark reactions are dependent on light, either directly or indirectly Neither the light reactions nor the dark reactions can occur in the absence of light

41. PHOTOSYNTHESIS Photosynthesis consists of two processes Light reactions a.k.a., Light-dependent reactions Dark reactions a.k.a., Light-independent reactions a.k.a., Calvin cycle Both the light reactions and the dark reactions are dependent on light, either directly or indirectly Neither the light reactions nor the dark reactions can occur in the absence of light

42. LIGHT REACTIONS Sunlight is absorbed by chlorophyll pigments Light energy is used to produce high-energy molecules ATP NADPH O2 is produced as a waste product H2O ? � O2 + 2H+ + 2e-

43. CALVIN CYCLE The high energy molecules produced during the light reactions are used to reduce CO2 to glucose This glucose can be converted to other compounds (amino acids, etc.) This glucose can be oxidized to yield energy

44. ANOXYGENIC PHOTOSYNTHESIS The general formula for photosynthesis is: 6CO2 + 12H2X + energy ? glucose + 12X + 6H2O The �X� is generally oxygen (O) Electrons are removed from H2O to form O2 Purple sulfur bacteria cannot remove electrons from H2O H2 and H2S are used instead of H2O What is the overall formula in each of these cases?