Cellular Respiration Stage 1: Glycolysis

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 • generate only2 ATP for every 1 glucose • occurs in cytosol In thecytosol?Why doesthat makeevolutionarysense?

4. Glycolysis • 1. Both types of PATHWAYS BEGIN with Glycolysis. • 2. Glycolysis is a pathway in which One Six-Carbon Molecule of GLUCOSE is Oxidized to Produce Two Three-Carbon Molecules of PYRUVIC ACID OR PYRUVATE. • 3. The word "GLYCOLYSIS" means "The Splitting of Glucose".  In a series of Ten Reactions, a molecule of Glucose is split into Two identical smaller molecules, each called PYRUVIC ACID or PYRUVATE. • 4. GLYCOLYSIS IS THE PROCESS BY WHICH GLUCOSE IS CONVERTED TO PYRUVIC ACID, AND SOME OF ITS ENERGY IS RELEASED. • 5. Glycolysis occurs in the CYTOSOL OF THE CELL.

5. GLYCOLYSIS • 6. Whether or not Oxygen is present, Glycolysis SPLITS (BY OXIDATION) GLUCOSE INTO THREE-CARBON MOLECULES OF PGAL.  PGAL IS THEN CONVERTED TO THREE-CARBON PYRUVIC ACID. • 7. Glucose is a Stable molecule that DOES NOT Break down Easily. • 8. For a Molecule of Glucose to undergo Glycolysis, a Cell must First "SPEND" ATP to energize the Glucose Molecule.  The ATP provides the Activation Energy needed to begin Glycolysis. • 9. Although ATP (ENERGY) is used to begin Glycolysis, the reactions that make up the process eventually produce A NET GAIN OF TWO ATP MOLECULES. • 10. Glycolysis is followed BY THE BREAK DOWN OF PYRUVIC ACID.

6. FOUR MAIN STEPS • STEP 1 - TWO Phosphates are attached to Glucose, forming a NEW Six-Carbon Compound.  The Phosphate Groups come From TWO ATP, which are Converted to ADP. • STEP 2 - The Six-Carbon Compound formed in Step 1 is SPLIT into TWO Three-Carbon Molecules of PGAL. • STEP 3 - The TWO PGAL Molecules are Oxidized, and each Receives a Phosphate Group Forming Two NEW Three-Carbon Compounds.  The Phosphate Groups are provided by Two molecules of NAD+ forming NADH.

7. Steps cont • STEP 4 - The Phosphate Groups added in Step 1 and Step 3 are Removed from the Three-Carbon Compounds.  This reaction produces Two molecules of Pyruvic Acid.  Each Phosphate Group is combines with a molecule of ADP to make a molecule of ATP.  Because a total of Four Phosphate Groups were Added, FOUR MOLECULES OF ATP ARE PRODUCED. • TWO ATP Molecules were used in Step 1, but FOUR are Produced in Step 4.  Therefore, Glycolysis has a NET YIELD of TWO ATP Molecules for every Molecule of Glucose that is converted into Pyruvic Acid.  What happens to the Pyruvic Acid depends on the Type of Cell and on whether Oxygen is present.

8. Evolutionary perspective • 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 • ALL cells still utilize glycolysis You meanwe’re related?Do I have to invitethem over for the holidays?

9. enzyme enzyme enzyme enzyme enzyme enzyme enzyme enzyme ATP ATP 4 2 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:4 ATP & 2 NADH • consumes:2 ATP • net:2 ATP & 2 NADH 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

10. Glycolysis summary endergonic invest some ATP ENERGY INVESTMENT G3P C-C-C-P exergonic harvest a little ATP & a little NADH ENERGY PAYOFF 4ATP like $$in the bank yield 2 ATP 2 NADH NET YIELD

11. 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

12. 2nd half of glycolysis (5 reactions) G3P C-C-C-P Energy Harvest • NADH production • G3P donates H • oxidize sugar • reduce NAD+ • NAD+ NADH • ATP production • G3P  pyruvate • PEP sugar donates P • ADP  ATP 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- phosphoglyceromutase 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

13. 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!

14. 2 ATP 2 ADP 4 ADP ATP 4 Energy accounting of glycolysis • Net gain = 2 ATP • some energy investment (-2 ATP) • small energy return (+4 ATP) • 1 6C sugar 2 3C sugars glucose      pyruvate 6C 3C 2x All that work! And that’s all I get?

15. 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!

16. DHAP G3P NAD+ Pi NAD+ Pi NADH NADH 1,3-BPG 1,3-BPG recycleNADH We can’t stop there! • Going to run out of NAD+ • without regenerating NAD+, energy production would stop! • another molecule must accept H from NADH Glycolysis glucose + 2ADP + 2Pi + 2 NAD+2pyruvate+2ATP+2NADH

17. recycleNADH How is NADH recycled to NAD+? with oxygen aerobic respiration without oxygen anaerobic respiration fermentation Another molecule must accept H from NADH pyruvate NAD+ H2O CO2 NADH NADH O2 acetaldehyde NADH acetyl-CoA NAD+ NAD+ lactate (lactic acid) which path you use depends on who you are… Krebs cycle ethanol

18. pyruvate  ethanol + CO2 3C 2C 1C pyruvate  lactic acid NADH NADH NAD+ NAD+ 3C 3C Fermentation (anaerobic) • Bacteria, yeast to glycolysis • beer, wine, bread • Animals, some fungi to glycolysis • cheese, anaerobic exercise (no O2)

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

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

21. O2 O2 Pyruvate is a branching point Pyruvate fermentation anaerobicrespiration mitochondria Kreb’s cycle aerobic respiration

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

23. 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?

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