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2007-2008 Cellular Respiration Stage 1: Glycolysis
2007-2008 What’s the point? The point is to make ATP ! ATP
Glycolysis  <ul><li>Breaking down glucose  </li></ul><ul><ul><li>“ glyco  –  lysis ” (splitting sugar) </li></ul></ul><ul>...
Evolutionary perspective <ul><li>Prokaryotes </li></ul><ul><ul><li>first cells had no organelles </li></ul></ul><ul><li>An...
<ul><li>10 reactions </li></ul><ul><ul><li>convert  glucose (6C)   to  2 pyruvate (3C)  </li></ul></ul><ul><ul><li>produce...
Glycolysis summary  endergonic invest some ATP exergonic harvest a little  ATP & a little NADH <ul><li>net yield </li></ul...
1st half of glycolysis  (5 reactions) P i 3 6 4,5 ADP NAD + Glucose hexokinase phosphoglucose isomerase phosphofructokinas...
2nd half of glycolysis  (5 reactions) <ul><ul><li>NADH production </li></ul></ul><ul><ul><ul><li>G3P donates H </li></ul><...
Substrate-level Phosphorylation <ul><li>In the last steps of glycolysis, where did the P come from to make ATP? </li></ul>...
Energy accounting of glycolysis  <ul><li>Net gain =  2 ATP + 2 NADH </li></ul><ul><ul><li>some energy investment ( -2 ATP ...
Is that all there is? <ul><li>Not a lot of energy… </li></ul><ul><ul><li>for 1 billon years +  this is how life on Earth s...
But can’t stop there ! <ul><li>Going to run out of NAD + </li></ul><ul><ul><li>without regenerating NAD + ,   energy produ...
How is NADH recycled to NAD + ? <ul><li>Another molecule must accept H from NADH </li></ul>NADH pyruvate acetyl-CoA lactat...
Fermentation (anaerobic) <ul><li>Bacteria, yeast </li></ul><ul><li>Animals, some fungi </li></ul><ul><ul><ul><li>beer, win...
Lactic Acid Fermentation <ul><li>Reversible process </li></ul><ul><ul><li>once O 2  is available, lactate is converted bac...
Pyruvate is a branching point <ul><li>Pyruvate </li></ul>mitochondria Krebs cycle aerobic respiration fermentation anaerob...
2007-2008 What’s the point? The point is to make ATP ! ATP
And how do we do that? <ul><li>ATP synthase </li></ul><ul><ul><li>set up a H +  gradient </li></ul></ul><ul><ul><li>allow ...
2007-2008 NO ! There’s still  more  to my  s tory ! Any Questions?
Alcohol Fermentation Count the carbons !   <ul><li>Dead end process </li></ul><ul><ul><li>at ~12% ethanol, kills yeast </l...
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Chapter 15 lecture 2

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  • Why does it make sense that this happens in the cytosol? Who evolved first?
  • The enzymes of glycolysis are very similar among all organisms. The genes that code for them are highly conserved. They are a good measure for evolutionary studies. Compare eukaryotes, bacteria &amp; archaea using glycolysis enzymes. Bacteria = 3.5 billion years ago glycolysis in cytosol = doesn’t require a membrane-bound organelle O 2 = 2.7 billion years ago photosynthetic bacteria / proto-blue-green algae Eukaryotes = 1.5 billion years ago membrane-bound organelles! Processes that all life/organisms share: Protein synthesis Glycolysis DNA replication
  • 1st ATP used is like a match to light a fire… initiation energy / activation energy. Destabilizes glucose enough to split it in two
  • Glucose is a stable molecule it needs an activation energy to break it apart. phosphorylate it = Pi comes from ATP. make NADH &amp; put it in the bank for later.
  • And that’s how life subsisted for a billion years. Until a certain bacteria ”learned” how to metabolize O 2 ; which was previously a poison. But now pyruvate is not the end of the process Pyruvate still has a lot of energy in it that has not been captured. It still has 3 carbons bonded together! There is still energy stored in those bonds. It can still be oxidized further.
  • So why does glycolysis still take place?
  • Count the carbons!! Lactic acid is not a dead end like ethanol. Once you have O 2 again, lactate is converted back to pyruvate by the liver and fed to the Kreb’s cycle.
  • Transcript of "Chapter 15 lecture 2"

    1. 1. 2007-2008 Cellular Respiration Stage 1: Glycolysis
    2. 2. 2007-2008 What’s the point? The point is to make ATP ! ATP
    3. 3. Glycolysis <ul><li>Breaking down glucose </li></ul><ul><ul><li>“ glyco – lysis ” (splitting sugar) </li></ul></ul><ul><ul><li>ancient pathway which harvests energy </li></ul></ul><ul><ul><ul><li>where energy transfer first evolved </li></ul></ul></ul><ul><ul><ul><li>transfer energy from organic molecules to ATP </li></ul></ul></ul><ul><ul><ul><li>still is starting point for ALL cellular respiration </li></ul></ul></ul><ul><ul><li>but it’s inefficient </li></ul></ul><ul><ul><ul><li>generate only 2 ATP for every 1 glucose </li></ul></ul></ul><ul><ul><li>occurs in cytosol </li></ul></ul>In the cytosol? Why does that make evolutionary sense? That’s not enough ATP for me ! glucose      pyruvate 2 x 6C 3C
    4. 4. Evolutionary perspective <ul><li>Prokaryotes </li></ul><ul><ul><li>first cells had no organelles </li></ul></ul><ul><li>Anaerobic atmosphere </li></ul><ul><ul><li>life on Earth first evolved without free oxygen (O 2 ) in atmosphere </li></ul></ul><ul><ul><li>energy had to be captured from organic molecules in absence of O 2 </li></ul></ul><ul><li>Prokaryotes that evolved glycolysis are ancestors of all modern life </li></ul><ul><ul><li>ALL cells still utilize glycolysis </li></ul></ul>You mean we’re related? Do I have to invite them over for the holidays? Enzymes of glycolysis are “well-conserved”
    5. 5. <ul><li>10 reactions </li></ul><ul><ul><li>convert glucose (6C) to 2 pyruvate (3C) </li></ul></ul><ul><ul><li>produces: 4 ATP & 2 NADH </li></ul></ul><ul><ul><li>consumes: 2 ATP </li></ul></ul><ul><ul><li>net yield: 2 ATP & 2 NADH </li></ul></ul>Overview glucose C-C-C-C-C-C fructose-1,6bP P- C-C-C-C-C-C -P DHAP P- C-C-C G3P C-C-C -P pyruvate C-C-C DHAP = dihydroxyacetone phosphate G3P = glyceraldehyde-3-phosphate ATP 2 ADP 2 ATP 4 ADP 4 NAD + 2 2 P i enzyme enzyme enzyme enzyme enzyme enzyme enzyme enzyme 2 P i 2 H 2
    6. 6. Glycolysis summary endergonic invest some ATP exergonic harvest a little ATP & a little NADH <ul><li>net yield </li></ul><ul><li>2 ATP </li></ul><ul><li>2 NADH </li></ul>4 ATP ENERGY INVESTMENT ENERGY PAYOFF G3P C-C-C -P NET YIELD like $$ in the bank -2 ATP
    7. 7. 1st half of glycolysis (5 reactions) P i 3 6 4,5 ADP NAD + Glucose hexokinase phosphoglucose isomerase phosphofructokinase Glyceraldehyde 3 -phosphate (G3P) Dihydroxyacetone phosphate Glucose 6-phosphate Fructose 6-phosphate Fructose 1,6-bisphosphate isomerase glyceraldehyde 3-phosphate dehydrogenase aldolase 1,3-Bisphosphoglycerate (BPG) 1,3-Bisphosphoglycerate (BPG) 1 2 ATP ADP ATP NADH NAD + NADH P i CH 2 C O CH 2 OH P O CH 2 O P O CHOH C CH 2 O P O CHOH CH 2 O P O CH 2 O P O P O CH 2 H CH 2 OH O CH 2 P O O CH 2 OH P O Glucose “priming” <ul><ul><li>get glucose ready to split </li></ul></ul><ul><ul><ul><li>phosphorylate glucose </li></ul></ul></ul><ul><ul><ul><li>molecular rearrangement </li></ul></ul></ul><ul><ul><li>split destabilized glucose </li></ul></ul>
    8. 8. 2nd half of glycolysis (5 reactions) <ul><ul><li>NADH production </li></ul></ul><ul><ul><ul><li>G3P donates H </li></ul></ul></ul><ul><ul><ul><li>oxidizes the sugar </li></ul></ul></ul><ul><ul><ul><li>reduces NAD + </li></ul></ul></ul><ul><ul><ul><li>NAD +  NADH </li></ul></ul></ul><ul><ul><li>ATP production </li></ul></ul><ul><ul><ul><li>G3P    pyruvate </li></ul></ul></ul><ul><ul><ul><li>PEP sugar donates P </li></ul></ul></ul><ul><ul><ul><ul><li>“ substrate level phosphorylation ” </li></ul></ul></ul></ul><ul><ul><ul><li>ADP  ATP </li></ul></ul></ul>Payola ! Finally some ATP ! 7 8 H 2 O 9 10 ADP ATP 3-Phosphoglycerate (3PG) 3-Phosphoglycerate (3PG) 2-Phosphoglycerate (2PG) 2-Phosphoglycerate (2PG) Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP) Pyruvate Pyruvate phosphoglycerate kinase phosphoglycero- mutase enolase pyruvate kinase ADP ATP ADP ATP ADP ATP H 2 O CH 2 OH CH 3 CH 2 O - O C P H CHOH O - O - O - C C C C C C P P O O O O O O CH 2 NAD + NADH NAD + NADH Energy Harvest G3P C-C-C -P P i P i 6 DHAP P- C-C-C
    9. 9. Substrate-level Phosphorylation <ul><li>In the last steps of glycolysis, where did the P come from to make ATP? </li></ul><ul><ul><li>the sugar substrate (PEP) </li></ul></ul><ul><li>P is transferred from PEP to ADP </li></ul><ul><ul><li>kinase enzyme </li></ul></ul><ul><ul><li>ADP  ATP </li></ul></ul>I get it! The P i came directly from the substrate ! ATP H 2 O 9 10 Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP) Pyruvate Pyruvate enolase pyruvate kinase ADP ATP ADP ATP H 2 O CH 3 O - O C O - C C C P O O O CH 2
    10. 10. Energy accounting of glycolysis <ul><li>Net gain = 2 ATP + 2 NADH </li></ul><ul><ul><li>some energy investment ( -2 ATP ) </li></ul></ul><ul><ul><li>small energy return ( 4 ATP + 2 NADH ) </li></ul></ul><ul><li>1 6C sugar  2 3C sugars </li></ul>glucose      pyruvate 2 x 6C 3C All that work! And that’s all I get? But glucose has so much more to give ! 2 ATP 2 ADP 4 ADP ATP 4 2 NAD + 2
    11. 11. Is that all there is? <ul><li>Not a lot of energy… </li></ul><ul><ul><li>for 1 billon years + this is how life on Earth survived </li></ul></ul><ul><ul><ul><li>no O 2 = slow growth, slow reproduction </li></ul></ul></ul><ul><ul><ul><li>only harvest 3.5% of energy stored in glucose </li></ul></ul></ul><ul><ul><ul><ul><li>more carbons to strip off = more energy to harvest </li></ul></ul></ul></ul>Hard way to make a living ! glucose     pyruvate 6C O 2 O 2 O 2 O 2 O 2 2 x 3C
    12. 12. But can’t stop there ! <ul><li>Going to run out of NAD + </li></ul><ul><ul><li>without regenerating NAD + , energy production would stop ! </li></ul></ul><ul><ul><li>another molecule must accept H from NADH </li></ul></ul><ul><ul><ul><li>so NAD + is freed up for another round </li></ul></ul></ul>Glycolysis glucose + 2ADP + 2P i + 2 NAD +  2 pyruvate + 2ATP + 2NADH raw materials  products 7 8 H 2 O 9 10 ADP ATP 3-Phosphoglycerate (3PG) 3-Phosphoglycerate (3PG) 2-Phosphoglycerate (2PG) 2-Phosphoglycerate (2PG) Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP) Pyruvate Pyruvate ADP ATP ADP ATP ADP ATP H 2 O NAD + NADH NAD + NADH P i P i 6 P i NAD + G3P 1,3-BPG 1,3-BPG NADH NAD + NADH P i DHAP
    13. 13. How is NADH recycled to NAD + ? <ul><li>Another molecule must accept H from NADH </li></ul>NADH pyruvate acetyl-CoA lactate ethanol NAD + NAD + NADH NAD + NADH CO 2 acetaldehyde H 2 O Krebs cycle O 2 lactic acid fermentation with oxygen aerobic respiration without oxygen anaerobic respiration “ fermentation ” which path you use depends on who you are… alcohol fermentation recycle NADH
    14. 14. Fermentation (anaerobic) <ul><li>Bacteria, yeast </li></ul><ul><li>Animals, some fungi </li></ul><ul><ul><ul><li>beer, wine, bread </li></ul></ul></ul><ul><ul><ul><li>cheese, anaerobic exercise (no O 2 ) </li></ul></ul></ul>back to glycolysis  back to glycolysis  1C 3C 2C pyruvate  ethanol + CO 2 pyruvate  lactic acid 3C 3C NADH NAD + NADH NAD +
    15. 15. Lactic Acid Fermentation <ul><li>Reversible process </li></ul><ul><ul><li>once O 2 is available, lactate is converted back to pyruvate by the liver </li></ul></ul> Count the carbons ! animals some fungi back to glycolysis  recycle NADH pyruvate  lactic acid 3C 3C NADH NAD + O 2
    16. 16. Pyruvate is a branching point <ul><li>Pyruvate </li></ul>mitochondria Krebs cycle aerobic respiration fermentation anaerobic respiration O 2 O 2
    17. 17. 2007-2008 What’s the point? The point is to make ATP ! ATP
    18. 18. And how do we do that? <ul><li>ATP synthase </li></ul><ul><ul><li>set up a H + gradient </li></ul></ul><ul><ul><li>allow H + to flow through ATP synthase </li></ul></ul><ul><ul><li>powers bonding of P i to ADP </li></ul></ul><ul><li> ADP + P i  ATP </li></ul>ATP But… Have we done that yet? ADP H + H + H + H + H + H + H + H + H + P +
    19. 19. 2007-2008 NO ! There’s still more to my s tory ! Any Questions?
    20. 20. Alcohol Fermentation Count the carbons ! <ul><li>Dead end process </li></ul><ul><ul><li>at ~12% ethanol, kills yeast </li></ul></ul><ul><ul><li>can’t reverse the reaction </li></ul></ul>bacteria yeast back to glycolysis  recycle NADH 1C 3C 2C pyruvate  ethanol + CO 2 NADH NAD +
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