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Lecture 9

Lecture 9: Glycolysis

Cells Get Energy by Oxidizing Stored Fat and Sugar to Make ATP

  • Sugars, fats, and to some extent proteins have bond energy that can be released by oxidation
  • Some of this energy can be trapped in the bonds of ATP so that it can be used to supply energy for cellular processes
  • Sugars (i.e., glycogen) and proteins have about 4 kcalories per gram of stored energy, while fats (triglycerides) have about 9 kcal/gram
  • If glucose is heated in the presence of oxygen it will burn in a single step reaction, releasing 686 kcal/mole of free energy as heat
  • This amount of energy, released at one time, is too large for most biological reactions

Cells Oxidize Sugars in Small Steps in Water at Low Temperature

  • Cells "burn" glucose at low temperature
  • Glucose is oxidized to pyruvate in 10 steps, releasing small amounts of energy at each step
  • Pyruvate is further oxidized in most eukaryotic cells to CO2 and water; this takes another 9 steps
  • Further steps in the electron transport system trap energy in ATP bonds
  • The final products of biological oxidation (CO2 and water) are the same as those obtained by high temperature burning, but much of the energy is trapped in ATP bonds
  • If you think of glucose as a tree, then biological oxidation is a bit like chopping the tree into logs of convenient length for future use

In Metabolism Carbon is Oxidized by Removing Hydrogen Atoms or Adding Oxygen Atoms

  • Loss of an electron, producing an ion, is called oxidation
  • If an electron is shifted away from an atom it is also called oxidation even if the electron is not completeley removed
  • Oxygen is more electronegative than carbon (it has a greater affinity for electrons than carbon)
    • If carbon binds to oxygen the carbon is oxidized because electrons shift toward oxygen
    • In this reaction the oxygen is reduced
  • Hydrogen has less attraction for electrons than carbon
  • If carbon binds to a hydrogen the carbon is reduced and the hydrogen is oxidized

     

     

     

     Carbon is progressively oxidized as methane is converted to carbon dioxide. Note that each oxidation involves the addition of an oxygen atom or the removal of 2 hydrogen atoms.

     

     

In Biological Oxidations Hydrogen Atoms are Usually Transferred to Coenzymes

  • In biochemistry H atoms stripped from carbons are transferred to coenzymes derived from B vitamins
  • The enzymes removing the Hs are called dehydrogenases
  • Coenzymes are present in small amounts and must be recycled to keep reactions going
  • NADH and FADH2 are produced in glycolysis and respiration
    • They are usually recycled (to NAD+ and FAD) by the Electron Transport System of the mitochondria
    • These reactions produce large amounts of ATP

 Coenzyme  Source  Typical Reaction
 Nicotinamide Adenine
Dinucleotide		  Niacin

 

 Flavin Adenine
Dinucleotide		  Riboflavin

 

 Nicotinamide Adenine
Dinucleotide Phosphate		  Niacin

 

An Overview of Energy Metabolism

  • The figure shows the central pathways supplying energy in plant, animal and many other types of cells
    • In glycolysis glucose is oxidized through a series of steps to 2 pyruvic acids (pyruvate)
      • Takes place in cytosol
      • Yields a net of 2 ATPs and 2 NADHs per glucose
    • Pyruvate enters mitochondria where it is decarboxylated to produce acetyl CoA
      • This reaction yields 2 NADHs for the 2 pyruvates coming from each glucose
    • Acetyl CoA enters the Krebs cycle (also called the citric acid cycle) where it is oxidized to CO2
      • The yield (per original glucose) is 6 NADH, 2 FADH2 and 2 ATPs
    • The 10 NADHs and 2 FADH2s produced in the above processes are "cashed in" in the electron transport system to give 32 ATPs
      • The total yield of ATPs is 36 per glucose
  • The figure shows where fats and proteins enter the energy-producing reactions
    • Fatty acids are broken down in the mitochondria to acetyl CoA, which can enter the Krebs cycle
    • Amino acids enter the reactions at several locations, glycolysis, acetyl CoA and the Krebs cycle (this is because there are 20 different types of amino acids)

Glycolysis Converts Glucose to Pyruvate in 10 Steps, Yielding 2 ATPs and 2 NADHs

 6 CARBON
COMPOUNDS

 3 CARBON
COMPOUNDS

   

  GLUCOSE

    
     

 

  

 -ATP

  
   

 GLUCOSE-6-PHOSPHATE

    
     

 

      
   

 FRUCTOSE-6-PHOSPHATE

    
     

 

  

 -ATP

  
   

 FRUCTOSE-1, 6-DIPHOSPHATE

    
   

 

  

 

    
 

 

    

 DIHYDROXYACETONE
PHOSPHATE

       

 

  

 GLYCERALDEHYDE
3-PHOSPHATE

      

GLYCERALDEHYDE
3-PHOSPHATE

 

 

  +NADH  

+NADH

 

  

 1, 3-DIPHOSPHO-
GLYCERATE

      

 1, 3-DIPHOSPHO-
GLYCERATE

 

 

 +ATP

  

 +ATP

 

  

 3-PHOSPHOGLYCERATE

      

 3-PHOSPHOGLYCERATE

 

 

      

 

  

 2-PHOSPHOGLYCERATE

    

 2-PHOSPHOGLYCERATE

 

 

      

 

  

 PHOSPHOENOL-
PYRUVATE

      

  PHOSPHOENOL-
PYRUVATE

 

 

 +ATP

  

 +ATP

 

  

 PYRUVATE

      

 PYRUVATE

  • Glucose comes from 2 locations
    • From outside the cell- requires facilitated diffusion transport system
    • From glycogen stored within the cell
  • First 3 reactions use 2 ATPs to attach phospate groups to both ends of the glucose molecule
  • The 4th reaction, catalyzed by the enzyme aldolase, splits the 6 carbon glucose into two 3 carbon molecules, dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G-3-P)
    • The DHAP is converted to G-3-P by an isomerase enzyme, so you end up with 2 G-3-Ps
    • All of the reactions to now prepare the molecule. Up to this point we have lost 2 ATPs.
  • In 3 of the remaining 5 steps energy is trapped for the cells use. 4 ATPs are formed, paying back the 2 used in the earlier steps with a profit of 2 ATPs. In addition 2 NADHs are formed. If the cell has an electron transport system and if O2 is available, these can be used to produce an additional 4 ATPs.
  • The NADHs are formed in the reaction catalyzed by triose phosphate dehydrogenase, which oxidizes an aldehyde group to a carboxyl.
    • Phosphate (from inorganic phosphate, not ATP) reacts with the carboxyl to put a phosphate at both ends of the molecule.
    • These 2 phosphates are the ones that produce ATP in reactions controlled by phosphoglycerokinase and pyruvate kinase.
    • This is called substrate level phosphorylation because the electron transport system of the mitochondrion is not involved
  • If you really want to understand the chemistry of glycolysis go to John Maber's Do It Yourself Glycolysis site (University of Leeds).

If Oxygen is Absent the Pyruvic Acid is Converted to Lactic Acid or Ethanol

  • The triose phosphate dehydrogenase reaction requires NAD+. If none is present glycolysis will be blocked and glyceraldehyde-3-phosphate will pile up
  • In mammalian cells if there is no oxygen the NADH will give its hydrogen to pyruvic acid, converting it to lactic acid.
  • This regenerates NAD+, allowing glycolysis to continue
  • In other species, such as yeast, NADH donates Hs to acetaldehyde, producing ethanol

If Oxygen is Present the NADHs Can be Used to Generate More ATP

  • If the cell has mitochondria (most eukaryotic cells) and oxygen is available then NADH will deliver its hydrogens to the electron transport system
  • The released energy can be used to synthesize ATP
  • NAD+ is produced and glycolysis continues

Glycolysis is Regulated at Several Sites

  • The cell cannot store much ATP, so its production must be controlled by current needs
  • One way in which this is done is by negative feedback by products of the reactions
  • Example:Phosphofructokinase, which catalyzes 3rd reaction of glycolysis
    • Inhibited by high ATP levels and by citric acid (a Krebs cycle intermediate)
    • Activated by high levels of ADP
  • Hexokinase and pyruvate kinase, which catalyze the 1st and last steps of glycolysis, are also regulated enzymes

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