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Krebs Cycle (Citric Acid Cycle)
              &
   Quick and Long Energy
Glycolysis



Glucose
                                     2 molecules of
                                        pyruvate




                  To the electron transport chain
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
Krebs Cycle

• British biochemist Hans Krebs, discovered
  1937
• During Krebs cycle, PYRUVATE is broken
  down into CARBON DIOXIDE in a series
  of energy extracting reactions
• AKA the CITRIC ACID CYCLE because
  citrate (also called citric acid) is the first
  product of the cycle
From Glycolysis comes the
      Pyruvates….
Krebs Cycle
• Citric Acid Production
                               Step 1
   – Pyruvate ( 3-carbons) enter
      mitochondria Matrix
   – One carbon is removed as CO2
      (WASTE product) and electrons
      are removed by NAD+ (making
      NADH which goes to the ETC)
   – Co-enzyme A joins the 2-carbon
      molecule (that used to be
      pyruvate) making Acetyl-CoA
   – Now Acetyl-CoA can enter the
      Krebs cycle
   – Acetyl Co-A combines with 4-
      carbon molecule called
      OXALOACETATE , making
      citrate (citric acid), a 6-carbon
      molecule
Step 2
• Citric acid (6 carbon molecule) is
  broken down into a few different
  5-carbon compounds, then into a
  few different 4-carbon
  compounds.
• Each step releases CO2, NADH
  and FADH2, and ATP
   – CO2 is a waste product
      (breath out!)
   – NADH and FADH2 (taxi cabs)
      goes onto the ETC (where
      the party is at)
   – ATP is used for cell to do
      work (mechanical, chemical,
      or transport)
Count the carbons!
           pyruvate                  acetyl CoA
                      3C        2C
                                           citrate
                           4C         6C


                 4C         oxidation          6C
This happens
twice for each              of sugars
                                                           CO2
glucose
molecule                        x2
                 4C                             5C


                           4C         4C             CO2
Count the electron carriers!                          CO2
           pyruvate                   acetyl CoA
                      3C         2C
                                                        NADH
                                            citrate
           NADH            4C          6C


                  4C       reduction            6C
This happens               of electron
twice for each             carriers                          CO2
glucose
                                                             NADH
molecule                         x2              5C
                  4C
          FADH2                                         CO2
                           4C          4C
                                                      NADH
                                ATP
So we fully
oxidized
(broke down)
glucose
C6H12O6

CO2
& ended up
with 4 ATP!

      What’s the
      point?
Electron Carriers = Hydrogen Carriers
                                    H+
                                                 H+

 Krebs cycle
                                         H+ H+
                                               +
                                    H+    H+ H H+



 produces large
 quantities of
 electron carriers           ADP
                             + Pi

   NADH                        ATP
                                              H+


   FADH2

   go to Electron

    Transport Chain!

      What’s so
      important about
      electron carriers?
Energy accounting of Krebs
              cycle
     4 NAD + 1 FAD    4 NADH + 1 FADH2

2x pyruvate                     CO2
      3C                        3x 1C
              1 ADP   1 ATP
                         ATP


  Net gain = 2 ATP
           = 8 NADH + 2 FADH2
Value of Krebs cycle?
• If the yield is only 2 ATP then how was the Krebs
  cycle an adaptation?
   – value of NADH & FADH2
     • electron carriers & H carriers
     • to be used in the Electron Transport Chain




                                   like $$
                                   in the
                                   bank
Summary
• In one turn of the Krebs • For one Glucose
  Cycle:                          molecule how many
   – 3 CO2 (1 from right          times does the Krebs
     before Krebs)                Cycle turn?
      • Released when we exhale
                                • What are the totals
   – 1 ATP (E for cell work)
                                  from the Krebs Cycle
   – 1 NADH from right before
     Krebs                        for one Glucose
   – 3 NADH from Krebs (to        molecule?
     ETC)                       –   6 CO2s
   – 1 FADH2 (to ETC)           –   2 ATPs
   – Water leaves and then      –   8 NADHS
     reenters so we don’t       –   2 FADH2
     count it in the products
So we use Krebs if we have
  oxygen….what if there is NO
         oxygen???
• Then we can’t even enter the mitochondria
  and go to the Krebs cycle…
• We are stuck using Glycolysis…
• Anaerobic respiration (NO oxygen)
  – 2 types
    • Lactic acid fermentation
    • Alcohol fermentation
Pyruvate is a branching point
       Pyruvate

       O2    O2

fermentation
anaerobic
respiration
          mitochondria
          Krebs cycle
          aerobic respiration
or
2
• Cells cannot get enough oxygen
• Build up of pyruvic acid and NADH and no oxygen to break it down
• Cells begin fermentation
   – Lactic Acid fermentation
       • Pyruvic acid + NADH lactic acid + NAD+
       • Get about 90 seconds of energy without having to use oxygen
       • HOWEVER, oxygen will be paid back double when you are done
         (think heavy breathing)
       • Occurs in muscle cells, and microorganisms, such as the ones that
         turn milk into cheese and yogurt
       • Lactic acid causes muscle cramping and burning sensation
       • Oxygen is required to break down lactic acid and get it out of body
   – Alcohol fermentation
       • Pyruvic acid + NADH ethyl alcohol + NAD+ + CO2
       • Occurs in yeast cells and other microorganisms, such as the ones
         involved in the production of bread and wine
How is NADH recycled to NAD+?
                     with oxygen               without oxygen
Another molecule aerobic respiration           anaerobic respiration
must accept H from pyruvate                    “fermentation”
NADH
               H2O   NAD+
                                                                 CO2

               O2    NADH           NADH               acetaldehyde

  recycle              acetyl-CoA                     NADH
                                    NAD+
  NADH
                                         lactate      NAD+
                                       lactic acid
                                       fermentation
which path you            Krebs
                          cycle                           ethanol
use depends on                                         alcohol
who you are…                                           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        NAD+
                          back to glycolysis
  cheese, anaerobic exercise (no O2)
Alcohol Fermentation                    bacteria 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!
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!
Quick Energy
•   3 ways to obtain energy
     – ATP stored in muscles (glycogen) (short)
     – ATP from lactic acid (short)
     – ATP from cellular respiration (long)
•   Cells initially have small amount of ATP from cell resp. and glycolysis
•   Think of running a 200 m sprint
     – Gun goes off
           • Muscles of runner contract, turning glycogen in muscle cells into
               glucose, but this only provides for a few seconds of intense activity
     – You pass the 50m mark
           • most ATP the was initially stored is now gone
           • Muscle cells are producing ATP from lactic acid fermentation
           • This lasts about 90 seconds
     – End of Race
           • Lots of lactic acid build up
           • Only way to get rid of lactic acid is a chemical pathway that requires oxygen
           • Thus, at the end of the race, you are breathing heavily and you should follow
               an intense work out with a slow jog
Long Term
•   Energy for running long races or other endurance sports
•   Cellular respiration is the only way to get enough ATP to last the length of the race
•   Cellular respiration makes ATP more slowly than lactic acid fermentation
•   Athletes must pace themselves
•   Glycogen an important molecule
     –   Carbohydrate
     –   Polysaccharide (monosaccharide is glucose)
     –   Muscle and liver cells store E as glycogen
     –   Glycogen is broken down by the hormone Glucagon
     –   Glycogen break down is also stimulated by muscle contraction
           •   When you work out, muscles contract and they can use energy stored in glycogen
     –   Increase glycogen storage, increase the duration of exhaustive work your muscles can do
     –   Stores of glycogen last about 15-20 minutes
•   After glycogen is used up, body starts to break down other molecules to get energy
     –   Fats and proteins
     –   Fatty acids are broken down and carried to mitochondrial matrix and enter the membrane in fragments
         as acetyl-CoA
     –   Proteins are broken down into aa and the these modified aa’s are fed back into the Krebs cycle (NAD+
         and FAD)
•   Aerobic exercise is good for weight control because it leads to break down of fats
Training to Improve Function of
        ATP production
• Anaerobic training
  – Increase levels of glycogen in muscle cells
    and increase tolerance of lactic acid build up
• Aerobic training
  – Increases size and number of mitochondria in
    muscle cells and increase delivery of oxygen
    to muscle cells by improving heart and lung
    efficiency
What’s the
            point?


               The point
               is to make
               ATP!

      ATP
2007-2008

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Cell respiration part 2

  • 1. Krebs Cycle (Citric Acid Cycle) & Quick and Long Energy
  • 2. Glycolysis Glucose 2 molecules of pyruvate To the electron transport chain
  • 3. 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
  • 4. Krebs Cycle • British biochemist Hans Krebs, discovered 1937 • During Krebs cycle, PYRUVATE is broken down into CARBON DIOXIDE in a series of energy extracting reactions • AKA the CITRIC ACID CYCLE because citrate (also called citric acid) is the first product of the cycle
  • 5. From Glycolysis comes the Pyruvates….
  • 7. • Citric Acid Production Step 1 – Pyruvate ( 3-carbons) enter mitochondria Matrix – One carbon is removed as CO2 (WASTE product) and electrons are removed by NAD+ (making NADH which goes to the ETC) – Co-enzyme A joins the 2-carbon molecule (that used to be pyruvate) making Acetyl-CoA – Now Acetyl-CoA can enter the Krebs cycle – Acetyl Co-A combines with 4- carbon molecule called OXALOACETATE , making citrate (citric acid), a 6-carbon molecule
  • 8. Step 2 • Citric acid (6 carbon molecule) is broken down into a few different 5-carbon compounds, then into a few different 4-carbon compounds. • Each step releases CO2, NADH and FADH2, and ATP – CO2 is a waste product (breath out!) – NADH and FADH2 (taxi cabs) goes onto the ETC (where the party is at) – ATP is used for cell to do work (mechanical, chemical, or transport)
  • 9. Count the carbons! pyruvate acetyl CoA 3C 2C citrate 4C 6C 4C oxidation 6C This happens twice for each of sugars CO2 glucose molecule x2 4C 5C 4C 4C CO2
  • 10. Count the electron carriers! CO2 pyruvate acetyl CoA 3C 2C NADH citrate NADH 4C 6C 4C reduction 6C This happens of electron twice for each carriers CO2 glucose NADH molecule x2 5C 4C FADH2 CO2 4C 4C NADH ATP
  • 11. So we fully oxidized (broke down) glucose C6H12O6 CO2 & ended up with 4 ATP! What’s the point?
  • 12. Electron Carriers = Hydrogen Carriers H+ H+  Krebs cycle H+ H+ + H+ H+ H H+ produces large quantities of electron carriers ADP + Pi  NADH ATP H+  FADH2  go to Electron Transport Chain! What’s so important about electron carriers?
  • 13. Energy accounting of Krebs cycle 4 NAD + 1 FAD 4 NADH + 1 FADH2 2x pyruvate CO2 3C 3x 1C 1 ADP 1 ATP ATP Net gain = 2 ATP = 8 NADH + 2 FADH2
  • 14. Value of Krebs cycle? • If the yield is only 2 ATP then how was the Krebs cycle an adaptation? – value of NADH & FADH2 • electron carriers & H carriers • to be used in the Electron Transport Chain like $$ in the bank
  • 15.
  • 16. Summary • In one turn of the Krebs • For one Glucose Cycle: molecule how many – 3 CO2 (1 from right times does the Krebs before Krebs) Cycle turn? • Released when we exhale • What are the totals – 1 ATP (E for cell work) from the Krebs Cycle – 1 NADH from right before Krebs for one Glucose – 3 NADH from Krebs (to molecule? ETC) – 6 CO2s – 1 FADH2 (to ETC) – 2 ATPs – Water leaves and then – 8 NADHS reenters so we don’t – 2 FADH2 count it in the products
  • 17. So we use Krebs if we have oxygen….what if there is NO oxygen??? • Then we can’t even enter the mitochondria and go to the Krebs cycle… • We are stuck using Glycolysis… • Anaerobic respiration (NO oxygen) – 2 types • Lactic acid fermentation • Alcohol fermentation
  • 18. Pyruvate is a branching point Pyruvate O2 O2 fermentation anaerobic respiration mitochondria Krebs cycle aerobic respiration
  • 19. or 2
  • 20. • Cells cannot get enough oxygen • Build up of pyruvic acid and NADH and no oxygen to break it down • Cells begin fermentation – Lactic Acid fermentation • Pyruvic acid + NADH lactic acid + NAD+ • Get about 90 seconds of energy without having to use oxygen • HOWEVER, oxygen will be paid back double when you are done (think heavy breathing) • Occurs in muscle cells, and microorganisms, such as the ones that turn milk into cheese and yogurt • Lactic acid causes muscle cramping and burning sensation • Oxygen is required to break down lactic acid and get it out of body – Alcohol fermentation • Pyruvic acid + NADH ethyl alcohol + NAD+ + CO2 • Occurs in yeast cells and other microorganisms, such as the ones involved in the production of bread and wine
  • 21. How is NADH recycled to NAD+? with oxygen without oxygen Another molecule aerobic respiration anaerobic respiration must accept H from pyruvate “fermentation” NADH H2O NAD+ CO2 O2 NADH NADH acetaldehyde recycle acetyl-CoA NADH NAD+ NADH lactate NAD+ lactic acid fermentation which path you Krebs cycle ethanol use depends on alcohol who you are… fermentation
  • 22. 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 NAD+ back to glycolysis  cheese, anaerobic exercise (no O2)
  • 23. Alcohol Fermentation bacteria 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!
  • 24. 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!
  • 25. Quick Energy • 3 ways to obtain energy – ATP stored in muscles (glycogen) (short) – ATP from lactic acid (short) – ATP from cellular respiration (long) • Cells initially have small amount of ATP from cell resp. and glycolysis • Think of running a 200 m sprint – Gun goes off • Muscles of runner contract, turning glycogen in muscle cells into glucose, but this only provides for a few seconds of intense activity – You pass the 50m mark • most ATP the was initially stored is now gone • Muscle cells are producing ATP from lactic acid fermentation • This lasts about 90 seconds – End of Race • Lots of lactic acid build up • Only way to get rid of lactic acid is a chemical pathway that requires oxygen • Thus, at the end of the race, you are breathing heavily and you should follow an intense work out with a slow jog
  • 26.
  • 27.
  • 28. Long Term • Energy for running long races or other endurance sports • Cellular respiration is the only way to get enough ATP to last the length of the race • Cellular respiration makes ATP more slowly than lactic acid fermentation • Athletes must pace themselves • Glycogen an important molecule – Carbohydrate – Polysaccharide (monosaccharide is glucose) – Muscle and liver cells store E as glycogen – Glycogen is broken down by the hormone Glucagon – Glycogen break down is also stimulated by muscle contraction • When you work out, muscles contract and they can use energy stored in glycogen – Increase glycogen storage, increase the duration of exhaustive work your muscles can do – Stores of glycogen last about 15-20 minutes • After glycogen is used up, body starts to break down other molecules to get energy – Fats and proteins – Fatty acids are broken down and carried to mitochondrial matrix and enter the membrane in fragments as acetyl-CoA – Proteins are broken down into aa and the these modified aa’s are fed back into the Krebs cycle (NAD+ and FAD) • Aerobic exercise is good for weight control because it leads to break down of fats
  • 29. Training to Improve Function of ATP production • Anaerobic training – Increase levels of glycogen in muscle cells and increase tolerance of lactic acid build up • Aerobic training – Increases size and number of mitochondria in muscle cells and increase delivery of oxygen to muscle cells by improving heart and lung efficiency
  • 30. What’s the point? The point is to make ATP! ATP 2007-2008