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Energy transformation in living cell

Energy transformation in living cell. 10-19-2015. Life needs energy!. 食物分子中 生命不能利用 的化學能 , 經由細胞的代謝反應轉變成 生命可以利用 的化學能. Two kinds of energy source in living system:. 1, ATP: hydrolysis of “high energy bond” to generate energy 2, redox reaction: electron transfer

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Energy transformation in living cell

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  1. Energy transformation in living cell 10-19-2015

  2. Life needs energy! 食物分子中生命不能利用的化學能,經由細胞的代謝反應轉變成生命可以利用的化學能

  3. Two kinds of energy source in living system: 1, ATP: hydrolysis of “high energy bond” to generate energy 2, redox reaction: electron transfer - electron donor (H2, H2S, NADH etc.) - electron acceptor (Oxygen, S) - energy released during the electron transfer.

  4. Two kinds of energy source in living system: 1, ATP: hydrolysis of “high energy bond” to generate energy 2, redox reaction: electron transfer - electron donor (H2, H2S, NADH etc.) - electron acceptor (Oxygen, S) - energy released during the electron transfer.

  5. A very ancient invention (3.6 BY?): to save and to convert reducing power into ATP! Do you still remember the natural proton gradient in the lost city may be the energy source of the origin of life?

  6. Too large to be used!

  7. Dissecting glucose degradation into many steps. • In some key steps, a relative constant amount of energy will be released to generate one ATP or one NADH. • Energy stored in the structure of glucose is transformed into common currency of life.

  8. Activation of glucose by ATP?

  9. Complete oxidation of one mole of glucose will generate 686 kcal of heat or energy. In the absence of oxygen, glucose can only be degraded into pyruvate (glycolysis). One mole of glucose only produce two mole of ATP (7.3+7.3=14.6 kcal). The efficiency of energy preservation is only 2%. The first step of glucose degradation (glycolysis)

  10. How energy (electric potential) stored in NADH can be utilized? How does the product of glycolysis (pyruvic acid) be completely degraded? Life needs more efficient energy production!

  11. Two new features for energy transformation are invented: Krebs cycle and electron transport chain!

  12. The degradation of pyruvate through Krebs cycle produces large quantities of high energy electron (NADH and FADH2).

  13. How the high energy electron is utilized in the living cells?

  14. 粒腺體：細胞內的火力發電廠！ High energy electrons are transfer to oxygenin mitochondria to produce ATP . Electron donor: NADH/Electron acceptor: O2. How?

  15. High energy chemical intermediate (X) is formed during electron transfer from NADH to oxygen, then compound X transfer its energy to synthesis ATP. • You need to identify chemical nature of this putative intermediate. • This intermediate has never been found! • The Chemiosmotic Theory.

  16. The Chemiosmotic Theory (Nature 191, 144-148, 1961) By Peter Mitchell who won Nobel Prize in Chemistry in 1978

  17. Why life use proton gradient but not chemical compound as energy source to synthesize ATP?

  18. Substrate phosphorylation is stoichiometrical: Always one to one excahange!

  19. The total free energy from the movement of 1 mole of protons cross mitochondria membrane: 50 kJ/mol is required for ATP synthesis in mitochondria. Then you need translocate 3 protons in order to synthesize one ATP!

  20. Advantage to use proton gradient as energy storage for ATP synthesis • 10 protons will translocate per electron pair passed from NADH to O2. • 3 protons consumed per ATP synthesized. • (1 ATP/4 H+)/(10 H+/electron pair) = 2.5 ATP/electron pair. • No energy will lost or waste!

  21. High energy electron (NADH and FADH2) is converted to ATP through electron transport chain and proton gradient!

  22. When oxygen is not enough, Krebs cycle and ETC will not proceed! X If we want this pathway continue, what do we need?

  23. Why cells want to further convert pyruvate into lactate when oxygen is low?

  24. Krebs cycle and ETC X If we want this pathway continue, what do we need?

  25. We need supply of ADP and NAD! For ADP: no problem, but for NAD….

  26. For NAD+: In exhausted muscle: Not enough oxygen! When the supply of glucose is OK, even in the presence of oxygen, yeast still do fermentation:

  27. For NAD+: In exhausted muscle: Not enough oxygen! When the supply of glucose is OK, even in the presence of oxygen, yeast still do fermentation: Why? (Metabolite suppression)

  28. When LUCA left the lost city, they need an alternative energy sourceSUN LIGHT!

  29. 1, source of energy：photon from sun light 2, who absorbs the energy: chlorophyll molecule！ 3, how? Exciting electron of chlorophyll to higher energy level！ 4, who is the electron acceptor？Electron transport chain！

  30. Water is abundant !

  31. Chlorophyll: The most efficient molecule on earth to absorb light!

  32. Organization of photosystems in the thylakoid membrane: How the energy transfer is unidirectional ？

  33. Take two electrons from water and release one oxygen and two protons

  34. In green plant, two photosynthesis system (PSII and PSI) are coupled To generate proton gradient for ATP synthesis

  35. Photosynthesis • Light reactions: transform light (sunlight) energy into ATP and biosynthetic reducing power, NADPH. 2. Dark reactions (Calvin cycle): use ATP and NADPH to reduce CO2 to hexose

  36. Net reaction of the Calvin cycle 6 CO2 + 18 ATP +12 NADPH +12 H2O  C6H12O6 + 18 ADP + 18 Pi + 12 NADP+ + 6 H+ Incorporation of one CO2 into hexose uses 3 ATP and 2 NADPH (from light reaction)

  37. Ribulose 1,5-bisphosphate carboxlase/oxygenase (Rubisco): the most abundant protein on earth! 5C + 1C  2 x 3C

  38. Structure of Rubisco. Active site

  39. Acceleration of photosynthesis by concentrating CO2. Major site of photosynthesis PEP carboxylase vs NADP+-linked malate dehydrogenase

  40. Metabolism and Diseases Warburg effect: cancer cells produce lactic acid from glucose even under non-hypoxic conditions.

  41. 1883-1970

  42. The shortest grand proposal!

  43. Warburg effect: cancer cells produce lactic acid from glucose even oxygen supply is high.

  44. Why glucose does not go to TCA cycle in cancer cells ? Defect in mitochondria function or ?? Science 324: 1029-1033; 2009

  45. Pyruvate kinase (M1 and M2) • the M1 isoform is expressed in most adult tissues; and the M2 is a splice variant of M1 expressed during embryonic development • M1 is a constitutively active enzyme. M2 is a low activity enzyme. • Tumor tissues exclusively express the embryonic M2 isoform of pyruvate kinase. • What is the functional significance of expression of M2 of PK? • How cancer cell switch its PK gene expression from M1 to M2?

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