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Cellular Respiration
                 Stage 1:
                   Glycolysis



AP Biology                          2007-2008
What’s the
                    point?


                        The point
                       is to make
                          ATP!

             ATP
AP Biology                          2007-2008
Glycolysis
    Breaking down glucose
          “glyco – lysis” (splitting sugar)                           In the
                                                                      cytosol?
             glucose → → → → → pyruvate                              Why does
                                                                     that make
                6C             2x 3C                                evolutionary
                                                                       sense?
          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                    That’s not enough
AP Biology                                        ATP for me!
Evolutionary perspective
                                                       Enzymes
     Prokaryotes                                  of glycolysis are
            first cells had no organelles         “well-conserved”

     Anaerobic atmosphere
            life on Earth first evolved without free 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 mean
                                          we’re related?
                                        Do I have to invite
                                          them over for
AP Biology                                 the holidays?
glucose
     Overview                C-C-C-C-C-C
                                    enzyme         2 ATP
10 reactions
                                    enzyme         2 ADP
  convert            fructose-1,6bP
   glucose (6C) to P-C-C-C-C-C-C-P
   2 pyruvate (3C) enzyme          enzyme
                            enzyme
  produces:       DHAP              G3P
   4 ATP & 2 NADH P-C-C-C C-C-C-P                       2 NAD+
                                         2H
  consumes:                   2Pi enzyme
                                                        2
   2 ATP                           enzyme

  net yield:                            2Pi            4 ADP
                                   enzyme
   2 ATP & 2 NADH
                                             pyruvate   4 ATP
DHAP = dihydroxyacetone phosphate
G3P Biology
 AP
    = glyceraldehyde-3-phosphate              C-C-C
Glycolysis summary
ENERGY INVESTMENT                  endergonic
                                   invest some ATP

                          -2 ATP
                  G3P
ENERGY PAYOFF   C-C-C-P            exergonic
                                   harvest a little
                          4 ATP
                                   ATP & a little NADH
                                         like $$
                                         in the
                                           bank

NET YIELD                          net yield
                                   2 ATP
AP Biology                         2 NADH
1st half of glycolysis (5 reactions)
                                                                                  CH2OH
Glucose “priming”                       Glucose
                                             1
                                                                                          O
                                    ATP
                                             hexokinase
   get glucose ready               ADP                                            CH2 O       P
                                                                                       O
    to split                         Glucose 6-phosphate
                                               2
     phosphorylate                             phosphoglucose
                                                                              CH2 O       P
      glucose                                   isomerase
                                                                                  O           CH2OH
                                    Fructose 6-phosphate
     molecular                                3
                                   ATP
      rearrangement                            phosphofructokinase
                                                                        P O   CH2             CH2   O   P
                                   ADP                                                O
   split destabilized             Fructose 1,6-bisphosphate
    glucose                                  4,5 aldolase
                                                                                  H
                  P    O CH2              isomerase
                         C   O Dihydroxyacetone                                C O
                                                     Glyceraldehyde 3
                                                                              CHOH
                        CH2OH phosphate              -phosphate (G3P)
                                                                               CH2 O           P
                       NAD+             Pi   6    Pi         NAD+
                          NADH         glyceraldehyde        NADH
                                        3-phosphate                   P       O       O
                                       dehydrogenase
                      1,3-Bisphosphoglycerate 1,3-Bisphosphoglycerate         CHOH
AP Biology
                               (BPG)                   (BPG)                   CH2 O           P
2nd half of glycolysis (5 reactions)
                                        DHAP                    G3P
 Energy Harvest                        P-C-C-C                C-C-C-P
                                NAD+               Pi         Pi          NAD+
                                                        6
     NADH production           NADH                                      NADH
         G3P donates H         ADP                 7                     ADP
                                            phosphoglycerate                         O-
         oxidizes the sugar    ATP
                                                 kinase                   ATP        C
         reduces NAD+           3-Phosphoglycerate           3-Phosphoglycerate   CHOH
                                       (3PG)                        (3PG)
         NAD+ → NADH                              8
                                                                                    CH2        O P

                                                                                     O-
     ATP production                         phosphoglycero-
                                                 mutase                              C O
       G3P → → → pyruvate       2-Phosphoglycerate           2-Phosphoglycerate   H C O        P
                                       (2PG)                        (2PG)           CH2OH
       PEP sugar donates P
                                                       9                             O-
          “substrate level        H2O              enolase            H2O
                                                                                     C     O
             phosphorylation”                                                              O
                                                                                     C          P
       ADP → ATP               Phosphoenolpyruvate         Phosphoenolpyruvate
                                                                                     CH2
                                      (PEP)                       (PEP)

                                                    10                               O-
                                ADP                                       ADP
                                             pyruvate kinase
                  Payola!                                                 ATP
                                                                                     C     O
                                ATP
               Finally some                                                          C O
AP Biology         ATP!                 Pyruvate               Pyruvate              CH3
Substrate-level Phosphorylation
      In the last steps of glycolysis, where did
        the P come from to make ATP?
            the sugar substrate O
                                H
                                  (PEP) enolase
                                      2
                                           9
                                                                   H2O
                                                                               O-
                                                                               C     O
                                                                                     O
P is transferred                Phosphoenolpyruvate
                                      (PEP)
                                                         Phosphoenolpyruvate
                                                               (PEP)
                                                                               C
                                                                               CH2
                                                                                         P


from PEP to ADP                 ADP                   10               ADP
                                                                               O-

 kinase enzyme                 ATP
                                               pyruvate kinase
                                                                       ATP
                                                                               C     O
                                                                               C O
 ADP → ATP                               Pyruvate          Pyruvate           CH3

                       ATP

                  I get it!
                The Pi came
               directly from
               the substrate!
AP Biology
Energy accounting of glycolysis
               2 ATP      2 ADP

             glucose → → → → →
                   pyruvate
            6C              2x 3C

               4 ADP      4 ATP                 All that work!
                                                And that’s all
                                                     I get?
              2 NAD+      2                 But
                                        glucose has
                                       so much more
 Net gain = 2 ATP + 2 NADH               to give!
     some energy investment (-2 ATP)
     small energy return (4 ATP + 2 NADH)
 1 6C sugar → 2 3C sugars
AP Biology
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

 O2                  O2        glucose → → → → pyruvate
                                  6C            2x 3C
                        O2
                                              Hard way
O2                                            to make
                                              a living!
 AP Biology
                   O2
But can’t stop there!                  DHAP                              G3P
                                             NAD+                Pi       Pi               NAD+

       raw materials → products               NADH
                                              NAD+               Pi   6    Pi             NADH
                                                                                          NAD+
                                              NADH    1,3-BPG                  1,3-BPG     NADH

                                              ADP                     7                    ADP


Glycolysis                                     ATP                                         ATP
                                               3-Phosphoglycerate         3-Phosphoglycerate
                                                     (3PG)                      (3PG)
glucose + 2ADP + 2Pi + 2 NAD+ → 2 pyruvate + 2ATP + 2NADH
                                              8



                                               2-Phosphoglycerate         2-Phosphoglycerate
 Going to run out of NAD+                           (2PG)
                                                                      9
                                                                                (2PG)

                                                    H2O                                  H2O
      without regenerating NAD+,
       energy production would stop! Phosphoenolpyruvate                  Phosphoenolpyruvate
                                           (PEP)                                (PEP)
      another molecule must accept HADP               10                                  ADP

       from NADH                     ATP                                                   ATP

         so                                          Pyruvate                 Pyruvate
  AP Biology   NAD+ is freed up for another round
How is NADH recycled to NAD+?
                      with oxygen                       without oxygen
Another molecule   aerobic respiration           anaerobic respiration
must accept H         pyruvate
                                                        “fermentation”
from NADH
            H2O    NAD+
                                                                     CO2

            O2     NADH             NADH                  acetaldehyde

  recycle            acetyl-CoA                          NADH
                                    NAD+
   NADH
                                           lactate       NAD+
                                          lactic acid
                                         fermentation
which path you          Krebs
                                                              ethanol
use depends on          cycle
                                                              alcohol
who you are…
 AP Biology                                                fermentation
Fermentation (anaerobic)
     Bacteria, yeast
             pyruvate → ethanol + CO2
                 3C            2C          1C
                   NADH    NAD+
                                  back to glycolysis→→
         beer, wine, bread


      Animals, some fungi
             pyruvate → lactic acid
                 3C               3C
                   NADH    NADback to glycolysis→→
                              +



         
AP Biology   cheese, anaerobic exercise (no O2)
bacteria
   Alcohol Fermentation                                      yeast
                                                     recycle
      pyruvate → ethanol + CO2                        NADH
             3C              2C          1C
             NADH        NAD+ back to glycolysis→→

 Dead end process
    at ~12% ethanol,
     kills yeast
    can’t reverse the
     reaction
             Count the
             carbons!



AP Biology
animals
                                                          some fungi
   Lactic Acid Fermentation                           recycle
                                           O2
     pyruvate → lactic acid
                     →
                                                       NADH
             3C                3C
              NADH        NAD+ back to glycolysis→→

 Reversible process
    once O2 is available,
     lactate is converted
     back to pyruvate by
     the liver

              Count the
              carbons!

AP Biology
Pyruvate is a branching point
              Pyruvate

              O2     O2

fermentation
  anaerobic
 respiration
                      mitochondria
                      Krebs cycle
                   aerobic respiration

 AP Biology
What’s the
                    point?


                        The point
                       is to make
                          ATP!

             ATP
AP Biology                          2007-2008
H+
                                         H+       H+         H+
  And how do we do that? H          +              H+
                                              H
                                              +
                                                             H+

 ATP synthase
   set up a H+ gradient
   allow H+ to flow

    through ATP synthase
   powers bonding

    of Pi to ADP
                         ADP + P

   ADP + Pi → ATP             ATP
                                                        H+


But… Have we done that yet?
AP Biology
NO!
             There’s still more
               to my story!
              Any Questions?




AP Biology                    2007-2008

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Glycolysis

  • 1. Cellular Respiration Stage 1: Glycolysis AP Biology 2007-2008
  • 2. What’s the point? The point is to make ATP! ATP AP Biology 2007-2008
  • 3. Glycolysis  Breaking down glucose  “glyco – lysis” (splitting sugar) In the cytosol? glucose → → → → → pyruvate Why does that make 6C 2x 3C evolutionary sense?  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 That’s not enough AP Biology ATP for me!
  • 4. Evolutionary perspective Enzymes  Prokaryotes of glycolysis are  first cells had no organelles “well-conserved”  Anaerobic atmosphere  life on Earth first evolved without free 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 mean we’re related? Do I have to invite them over for AP Biology the holidays?
  • 5. glucose Overview C-C-C-C-C-C enzyme 2 ATP 10 reactions enzyme 2 ADP  convert fructose-1,6bP glucose (6C) to P-C-C-C-C-C-C-P 2 pyruvate (3C) enzyme enzyme enzyme  produces: DHAP G3P 4 ATP & 2 NADH P-C-C-C C-C-C-P 2 NAD+ 2H  consumes: 2Pi enzyme 2 2 ATP enzyme  net yield: 2Pi 4 ADP enzyme 2 ATP & 2 NADH pyruvate 4 ATP DHAP = dihydroxyacetone phosphate G3P Biology AP = glyceraldehyde-3-phosphate C-C-C
  • 6. Glycolysis summary ENERGY INVESTMENT endergonic invest some ATP -2 ATP G3P ENERGY PAYOFF C-C-C-P exergonic harvest a little 4 ATP ATP & a little NADH like $$ in the bank NET YIELD net yield 2 ATP AP Biology 2 NADH
  • 7. 1st half of glycolysis (5 reactions) CH2OH Glucose “priming” Glucose 1 O ATP hexokinase  get glucose ready ADP CH2 O P O to split Glucose 6-phosphate 2  phosphorylate phosphoglucose CH2 O P glucose isomerase O CH2OH Fructose 6-phosphate  molecular 3 ATP rearrangement phosphofructokinase P O CH2 CH2 O P ADP O  split destabilized Fructose 1,6-bisphosphate glucose 4,5 aldolase H P O CH2 isomerase C O Dihydroxyacetone C O Glyceraldehyde 3 CHOH CH2OH phosphate -phosphate (G3P) CH2 O P NAD+ Pi 6 Pi NAD+ NADH glyceraldehyde NADH 3-phosphate P O O dehydrogenase 1,3-Bisphosphoglycerate 1,3-Bisphosphoglycerate CHOH AP Biology (BPG) (BPG) CH2 O P
  • 8. 2nd half of glycolysis (5 reactions) DHAP G3P Energy Harvest P-C-C-C C-C-C-P NAD+ Pi Pi NAD+ 6  NADH production NADH NADH  G3P donates H ADP 7 ADP phosphoglycerate O-  oxidizes the sugar ATP kinase ATP C  reduces NAD+ 3-Phosphoglycerate 3-Phosphoglycerate CHOH (3PG) (3PG)  NAD+ → NADH 8 CH2 O P O-  ATP production phosphoglycero- mutase C O  G3P → → → pyruvate 2-Phosphoglycerate 2-Phosphoglycerate H C O P (2PG) (2PG) CH2OH  PEP sugar donates P 9 O-  “substrate level H2O enolase H2O C O phosphorylation” O C P  ADP → ATP Phosphoenolpyruvate Phosphoenolpyruvate CH2 (PEP) (PEP) 10 O- ADP ADP pyruvate kinase Payola! ATP C O ATP Finally some C O AP Biology ATP! Pyruvate Pyruvate CH3
  • 9. Substrate-level Phosphorylation  In the last steps of glycolysis, where did the P come from to make ATP?  the sugar substrate O H (PEP) enolase 2 9 H2O O- C O O P is transferred Phosphoenolpyruvate (PEP) Phosphoenolpyruvate (PEP) C CH2 P from PEP to ADP ADP 10 ADP O- kinase enzyme ATP pyruvate kinase ATP C O C O ADP → ATP Pyruvate Pyruvate CH3 ATP I get it! The Pi came directly from the substrate! AP Biology
  • 10. Energy accounting of glycolysis 2 ATP 2 ADP glucose → → → → → pyruvate 6C 2x 3C 4 ADP 4 ATP All that work! And that’s all I get? 2 NAD+ 2 But glucose has so much more  Net gain = 2 ATP + 2 NADH to give!  some energy investment (-2 ATP)  small energy return (4 ATP + 2 NADH)  1 6C sugar → 2 3C sugars AP Biology
  • 11. 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 O2 O2 glucose → → → → pyruvate 6C 2x 3C O2 Hard way O2 to make a living! AP Biology O2
  • 12. But can’t stop there! DHAP G3P NAD+ Pi Pi NAD+ raw materials → products NADH NAD+ Pi 6 Pi NADH NAD+ NADH 1,3-BPG 1,3-BPG NADH ADP 7 ADP Glycolysis ATP ATP 3-Phosphoglycerate 3-Phosphoglycerate (3PG) (3PG) glucose + 2ADP + 2Pi + 2 NAD+ → 2 pyruvate + 2ATP + 2NADH 8 2-Phosphoglycerate 2-Phosphoglycerate  Going to run out of NAD+ (2PG) 9 (2PG) H2O H2O  without regenerating NAD+, energy production would stop! Phosphoenolpyruvate Phosphoenolpyruvate (PEP) (PEP)  another molecule must accept HADP 10 ADP from NADH ATP ATP  so Pyruvate Pyruvate AP Biology NAD+ is freed up for another round
  • 13. How is NADH recycled to NAD+? with oxygen without oxygen Another molecule aerobic respiration anaerobic respiration must accept H pyruvate “fermentation” from NADH H2O NAD+ CO2 O2 NADH NADH acetaldehyde recycle acetyl-CoA NADH NAD+ NADH lactate NAD+ lactic acid fermentation which path you Krebs ethanol use depends on cycle alcohol who you are… AP Biology fermentation
  • 14. Fermentation (anaerobic)  Bacteria, yeast pyruvate → ethanol + CO2 3C 2C 1C NADH NAD+ back to glycolysis→→  beer, wine, bread  Animals, some fungi pyruvate → lactic acid 3C 3C NADH NADback to glycolysis→→ +  AP Biology cheese, anaerobic exercise (no O2)
  • 15. bacteria Alcohol Fermentation yeast recycle pyruvate → ethanol + CO2 NADH 3C 2C 1C NADH NAD+ back to glycolysis→→  Dead end process  at ~12% ethanol, kills yeast  can’t reverse the reaction Count the carbons! AP Biology
  • 16. animals some fungi Lactic Acid Fermentation recycle O2 pyruvate → lactic acid → NADH 3C 3C NADH NAD+ back to glycolysis→→  Reversible process  once O2 is available, lactate is converted back to pyruvate by the liver Count the carbons! AP Biology
  • 17. Pyruvate is a branching point Pyruvate O2 O2 fermentation anaerobic respiration mitochondria Krebs cycle aerobic respiration AP Biology
  • 18. What’s the point? The point is to make ATP! ATP AP Biology 2007-2008
  • 19. H+ H+ H+ H+ And how do we do that? H + H+ H + H+  ATP synthase  set up a H+ gradient  allow H+ to flow through ATP synthase  powers bonding of Pi to ADP ADP + P ADP + Pi → ATP ATP H+ But… Have we done that yet? AP Biology
  • 20. NO! There’s still more to my story! Any Questions? AP Biology 2007-2008

Editor's Notes

  1. Why does it make sense that this happens in the cytosol? Who evolved first?
  2. 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
  3. 1st ATP used is like a match to light a fire… initiation energy / activation energy. Destabilizes glucose enough to split it in two
  4. 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.
  5. 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.
  6. So why does glycolysis still take place?
  7. 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.