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Cellular Respiration Stage 1: Glycolysis

Glycolysis is the initial stage of cellular respiration where glucose, a 6-carbon sugar, is broken down into two 3-carbon pyruvate molecules, yielding a net gain of 2 ATP and 2 NADH. This ancient metabolic pathway occurs in the cytosol and is essential for all life forms, having evolved in an anaerobic environment where early prokaryotes captured energy without oxygen. Despite its inefficiency in energy production, glycolysis remains the starting point for aerobic respiration. Understanding glycolysis reveals its evolutionary significance and foundational role in energy metabolism.

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Cellular Respiration Stage 1: Glycolysis

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  1. Cellular RespirationStage 1:Glycolysis

  2. What’s thepoint? The pointis to makeATP! ATP

  3. glucose      pyruvate 6C 3C 2x 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 • ______________________________________ • occurs in cytosol In thecytosol?Why doesthat makeevolutionarysense? That’s not enoughATP for me!

  4. Evolutionary perspective Enzymesof glycolysis are“well-conserved” • Prokaryotes • first cells had no organelles • Anaerobic atmosphere • life on Earth first evolved withoutfree oxygen (O2) in atmosphere • energy had to be captured from organic molecules in absence of O2 • Prokaryotes that evolved glycolysis are ancestors of all modern life • ___________________________________________ You meanwe’re related?Do I have to invitethem over for the holidays?

  5. enzyme enzyme enzyme enzyme enzyme enzyme enzyme enzyme ATP ATP 2 4 2 2 4 ADP NAD+ ADP 2Pi 2 2H 2Pi glucose C-C-C-C-C-C Overview 10 reactions • convert glucose (6C)to 2 pyruvate (3C) • produces:_______________ • consumes:_______________ • net yield:_______________ 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

  6. Glycolysis summary _______________ invest some ATP ENERGY INVESTMENT -2 ATP G3P C-C-C-P _______________ harvest a little ATP & a little NADH ENERGY PAYOFF 4 ATP like $$in the bank _________ _________ _________ NET YIELD

  7. 1st half of glycolysis (5 reactions) CH2OH Glucose “priming” O Glucose 1 ATP hexokinase • get glucose ready to split • phosphorylate glucose • molecular rearrangement • split destabilized glucose ADP CH2 O P O Glucose 6-phosphate 2 phosphoglucose isomerase CH2 P O CH2OH O Fructose 6-phosphate 3 ATP phosphofructokinase P O CH2 CH2 O P O ADP Fructose 1,6-bisphosphate aldolase 4,5 H O CH2 P isomerase C O C O Dihydroxyacetone phosphate Glyceraldehyde 3 -phosphate (G3P) CHOH CH2OH CH2 O P NAD+ Pi NAD+ Pi 6 glyceraldehyde 3-phosphate dehydrogenase NADH NADH P O O CHOH 1,3-Bisphosphoglycerate (BPG) 1,3-Bisphosphoglycerate (BPG) CH2 O P

  8. 2nd half of glycolysis (5 reactions) DHAP P-C-C-C G3P C-C-C-P Energy Harvest • NADH production • G3P donates H • oxidizes the sugar • reduces NAD+ • __________________ • ATP production • G3P    pyruvate • PEP sugar donates P • __________________________________ • __________________ Pi Pi NAD+ NAD+ 6 NADH NADH 7 ADP ADP O- phosphoglycerate kinase C ATP ATP CHOH 3-Phosphoglycerate (3PG) 3-Phosphoglycerate (3PG) CH2 P O 8 O- phosphoglycero-mutase O C H C O P 2-Phosphoglycerate (2PG) 2-Phosphoglycerate (2PG) CH2OH O- 9 H2O H2O enolase C O O C P Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP) CH2 O- 10 ADP ADP C O pyruvate kinase Payola!Finally some ATP! ATP ATP C O CH3 Pyruvate Pyruvate

  9. O- 9 H2O H2O enolase C O O C P Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP) CH2 O- 10 ADP ADP C O pyruvate kinase ATP ATP C O CH3 Pyruvate Pyruvate 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 ATP I get it! The PO4 camedirectly fromthe substrate!

  10. 2 ATP 2 ADP 2 NAD+ 4 ADP ATP 4 2 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 6C 3C 2x All that work! And that’s all I get? Butglucose hasso much moreto give!

  11. O2 O2 O2 O2 O2 3C 2x Is that all there is? • Not a lot of energy… • for 1 billon years+ this is how life on Earth survived • no O2= slow growth, slow reproduction • only harvest 3.5% of energy stored in glucose • more carbons to strip off = more energy to harvest glucose     pyruvate 6C Hard wayto makea living!

  12. DHAP G3P NAD+ Pi NAD+ Pi NADH NADH 1,3-BPG 1,3-BPG Pi Pi NAD+ NAD+ 6 NADH NADH 7 ADP ADP ATP ATP 3-Phosphoglycerate (3PG) 3-Phosphoglycerate (3PG) 8 2-Phosphoglycerate (2PG) 2-Phosphoglycerate (2PG) 9 H2O H2O Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP) 10 ADP ADP ATP ATP Pyruvate Pyruvate But can’t stop there! • Going to run out of NAD+ • ____________________________________________________ • another molecule must accept H from NADH • so NAD+ is freed up for another round raw materialsproducts Glycolysis glucose + 2ADP + 2Pi + 2 NAD+2pyruvate+2ATP+2NADH

  13. recycleNADH How is NADH recycled to NAD+? ___________________ ___________________ ___________________ ___________________ ___________________ Another molecule must accept H from NADH pyruvate NAD+ H2O CO2 NADH NADH O2 acetaldehyde NADH acetyl-CoA NAD+ NAD+ lactate ________________________ which path you use depends on who you are… Krebs cycle ethanol ________________________

  14. pyruvate  ethanol + CO2 3C 2C 1C pyruvate  lactic acid NADH NADH NAD+ NAD+ 3C 3C Fermentation (anaerobic) • _____________________ back to glycolysis • beer, wine, bread • _____________________ back to glycolysis • cheese, anaerobic exercise (no O2)

  15. pyruvate  ethanol + CO2 3C 2C 1C NADH NAD+ recycleNADH bacteria yeast Alcohol Fermentation back to glycolysis • Dead end process • at ~12% ethanol, kills yeast • can’t reverse the reaction Count thecarbons!

  16. O2 pyruvate  lactic acid NADH NAD+ 3C 3C recycleNADH animalssome fungi Lactic Acid Fermentation  back to glycolysis • Reversible process • once O2 is available, lactate is converted back to pyruvate by the liver Count thecarbons!

  17. O2 O2 Pyruvate is a branching point Pyruvate fermentation anaerobicrespiration mitochondria Krebs cycle aerobic respiration

  18. What’s thepoint? The pointis to makeATP! ATP

  19. H+ H+ H+ H+ H+ H+ H+ H+ + P H+ And how do we do that? • ATP synthase • set up a H+ gradient • allow H+ to flow through ATP synthase • powers bonding of Pi to ADP ADP + PiATP ADP ATP But… Have we done that yet?

  20. NO!There’s still more to my story! Any Questions?

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