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Glycolysis

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    1335
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    The essential metabolic pathway of glycolysis involves the oxidative breakdown of one glucose into two pyruvate with the capture of some energy as ATP and NADH. Glycolysis is important in the cell because glucose is the main source of fuel for tissues in the body.  For example, glucose is the only source of energy for the brain. To ensure normal brain function, the body must maintain a constant supply of glucose in the blood. Glycolysis is also important because the metabolism of glucose produces useful intermediates for other metabolic pathways, such as the synthesis of amino acids or fatty acids.  

    The major themes to remember when studying glycolysis include:

    • Glycolysis is a sequence of enzymatic reactions
    • ATP is invested, then recaptured with a net gain of 2 ATP
    • Pathway is regulated at key steps when ΔG << 0
    • Production of useful intermediates for other metabolic pathways

    Cellular respiration

    Glycolysis is the first step of cellular respiration

    1.  Glucose ---> 2 Pyruvate

    Anaerobic Respiration

    In the absence of oxygen pyruvate is converted into lactate or CO2 or malate

    Pyruvate + NADH ---> Lactate + NAD+

    Pyruvate ---> CO2 + acetaldehyde  + NADH ---> ethanol + NAD+

    Pyruvate + CO2 ---> OAA + NADH ---> Malate + NAD+

    OR

    Aerobic Respiration

    In the presence of oxygen pyruvate is converted into CO2 and H2

    Pyruvate ---> CO2 + H20

    Overall Reaction for Aerobic Cellular Respiration

    C6H12O6 + 6O2 ---> 6CO2 + 6H20

    ΔG= -2840 KJ/mol

    In respiration some ΔGo (~35%) is retained as formation as ATP 

    Priming: Investment of Energy (2 ATP):  There are five reactions during the priming phase

    Screen shot 2011-05-19 at 11.49.37 AM.pngpriming.png

    Note:  Mg2+ is required if ATP is needed (1 per ATP molecule)

    Reaction 1:  Hexokinase and Glucokinase pick up a phosphate from ATP and bind it to glucose.

    Screen shot 2011-05-19 at 11.50.26 AM.png

    • Reactions with an overall ΔG << 0 can be regulated (turn the enzyme on or off)
    • Hexokinase is allosterically inhibited by G-3-P (Km~o.1mM)
    • Glucokinase is not allosterically inhibited (Km ~10mM), keeps glucose in the cell 

     

    Reaction 2: Phosphoglucoisomerase converts glucose into fructose (changes the bonds around).

    Screen shot 2011-05-19 at 11.58.57 AM.png

    • Not regulated because ΔG is near equilibrium
       

     

    Reaction 3:  Phosphofructokinase picks up another phosphate from ATP and attaches it to fructose.

    Screen shot 2011-05-19 at 12.01.59 PM.png

    • ATP is an allosteric inhibitor 
    • AMP reverses ATP inhibition (if ATP decreases by 8%, AMP increase 4 fold)
    • AMP is the controlling factor of the enzyme
    • If ATP decreases and AMP increases, the reaction proceeds forward

     

    Reaction 4: Fructose biphosphate aldolase splits F-1,6-bisP into two 3 carbon compounds

    Screen shot 2011-05-19 at 12.12.09 PM.png

    Reaction 5:  Triose phosphate isomerase converts DHAP into G-3-P

    Screen shot 2011-05-19 at 12.13.12 PM.png

    ΔG of overall reaction:

    Screen shot 2011-05-19 at 12.14.11 PM.png

    Payoff: