Chapter 15 lecture 2
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Glycolysis is the first stage of cellular respiration where glucose is broken down to produce a small amount of ATP. It occurs in the cytosol of cells and was one of the earliest metabolic pathways to evolve in prokaryotes under anaerobic conditions. Glycolysis yields two ATP, two NADH, and two pyruvate molecules per glucose molecule. The NADH produced must be recycled to NAD+ to allow glycolysis to continue through pathways like lactic acid fermentation, alcohol fermentation or the Krebs cycle. While glycolysis yields little energy, it was crucial for early life and remains the initial pathway for all cellular respiration.
Chapter 15 lecture 2
- 1. 2007-2008 Cellular Respiration Stage 1: Glycolysis
- 2. 2007-2008 What’s the point? The point is to make ATP ! ATP
- 3. Glycolysis Breaking down glucose “ glyco – lysis ” (splitting sugar) ancient pathway which harvests energy where energy transfer first evolved transfer energy from organic molecules to ATP still is starting point for ALL cellular respiration but it’s inefficient generate only 2 ATP for every 1 glucose occurs in cytosol In the cytosol? Why does that make evolutionary sense? That’s not enough ATP for me ! glucose pyruvate 2 x 6C 3C
- 4. Evolutionary perspective Prokaryotes first cells had no organelles Anaerobic atmosphere life on Earth first evolved without free oxygen (O 2 ) in atmosphere energy had to be captured from organic molecules in absence of O 2 Prokaryotes that evolved glycolysis are ancestors of all modern life ALL cells still utilize glycolysis You mean we’re related? Do I have to invite them over for the holidays? Enzymes of glycolysis are “well-conserved”
- 5. 10 reactions convert glucose (6C) to 2 pyruvate (3C) produces: 4 ATP & 2 NADH consumes: 2 ATP net yield: 2 ATP & 2 NADH 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. Glycolysis summary endergonic invest some ATP exergonic harvest a little ATP & a little NADH net yield 2 ATP 2 NADH 4 ATP ENERGY INVESTMENT ENERGY PAYOFF G3P C-C-C -P NET YIELD like $$ in the bank -2 ATP
- 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” get glucose ready to split phosphorylate glucose molecular rearrangement split destabilized glucose
- 8. 2nd half of glycolysis (5 reactions) NADH production G3P donates H oxidizes the sugar reduces NAD + NAD + NADH ATP production G3P pyruvate PEP sugar donates P “ substrate level phosphorylation ” ADP ATP 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. Substrate-level Phosphorylation In the last steps of glycolysis, where did the P come from to make ATP? the sugar substrate (PEP) P is transferred from PEP to ADP kinase enzyme ADP ATP 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. Energy accounting of glycolysis Net gain = 2 ATP + 2 NADH some energy investment ( -2 ATP ) small energy return ( 4 ATP + 2 NADH ) 1 6C sugar 2 3C sugars 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. Is that all there is? Not a lot of energy… for 1 billon years + this is how life on Earth survived no O 2 = slow growth, slow reproduction only harvest 3.5% of energy stored in glucose more carbons to strip off = more energy to harvest Hard way to make a living ! glucose pyruvate 6C O 2 O 2 O 2 O 2 O 2 2 x 3C
- 12. But can’t stop there ! Going to run out of NAD + without regenerating NAD + , energy production would stop ! another molecule must accept H from NADH so NAD + is freed up for another round 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. How is NADH recycled to NAD + ? Another molecule must accept H from NADH 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. Fermentation (anaerobic) Bacteria, yeast Animals, some fungi beer, wine, bread cheese, anaerobic exercise (no O 2 ) back to glycolysis back to glycolysis 1C 3C 2C pyruvate ethanol + CO 2 pyruvate lactic acid 3C 3C NADH NAD + NADH NAD +
- 15. Lactic Acid Fermentation Reversible process once O 2 is available, lactate is converted back to pyruvate by the liver Count the carbons ! animals some fungi back to glycolysis recycle NADH pyruvate lactic acid 3C 3C NADH NAD + O 2
- 16. Pyruvate is a branching point Pyruvate mitochondria Krebs cycle aerobic respiration fermentation anaerobic respiration O 2 O 2
- 17. 2007-2008 What’s the point? The point is to make ATP ! ATP
- 18. And how do we do that? ATP synthase set up a H + gradient allow H + to flow through ATP synthase powers bonding of P i to ADP ADP + P i ATP ATP But… Have we done that yet? ADP H + H + H + H + H + H + H + H + H + P +
- 19. 2007-2008 NO ! There’s still more to my s tory ! Any Questions?
- 20. Alcohol Fermentation Count the carbons ! Dead end process at ~12% ethanol, kills yeast can’t reverse the reaction bacteria yeast back to glycolysis recycle NADH 1C 3C 2C pyruvate ethanol + CO 2 NADH NAD +
Editor's Notes
- #4: Why does it make sense that this happens in the cytosol? Who evolved first?
- #5: 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 & 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
- #6: 1st ATP used is like a match to light a fire… initiation energy / activation energy. Destabilizes glucose enough to split it in two
- #7: Glucose is a stable molecule it needs an activation energy to break it apart. phosphorylate it = Pi comes from ATP. make NADH & put it in the bank for later.
- #11: 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.
- #12: So why does glycolysis still take place?
- #15: 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.