The Design of Metabolism                                       
key concepts
*
            or How Biological Order Comes About...

METABOLISM.... the catalytic reactions (run by enzymes) of cells.....
                                             metabolic pathways [A --> B --> C --> D --> E]

  2 Categories catalytic reactions -
        CATABOLISM...  chemical oxidation of food stuffs or Cell Respiration
                 1)    digestion of polymers (foods)  [hydrolysis reactions] to glucose
                 2)   GLYCO-LYSIS   glucose ---> pyruvate    [splitting of sugar]
                 3)   KREBS cycle    oxidation of Acetyl-CoA  --->  CO2 + NADH ----> H2O
                 4)   ELECTRON TRANSFER ----> NADH + O2  ---->  H2O +  H+ gradient
                 5)   ATP SYNTHASE ---> use a H+ gradient to phosphorylate P + ADP ----> ATP
                                                                                                                   
   5 steps*
       ANABOLISM...   Biosynthesis, often via...
                                      coupled reactions - energetically unfavored  w  favored reactions
  flag18.gif (924 bytes)          1)   PHOTOSYNTHESIS    reduction of CO2 to CH2O

 

 

 

 

 

 

 
 
   
ENERGY (transformations)
       energy is capacity or ability to do work 
       kinds:   KINETIC - energy of motion motion
                   POTENTIAL - stored energy; capacity to do work (eventually);
                   HEAT - assoc with movement of molecules in a body of matter;
                                       most random form of energy (wasted).   
                                       Student Media Activities -
chapter 6A - Energy Transformations
  
                                EXAMPLES            general:  heat,  light,  sound,  mechanical
                                   of energy:       biological:  synthetic,  osmotic,  mechanical,
             
        molecules in living cells have chemical potential energy to do work...
                               because of the arrangement (orientation) of their atoms
                               in space... we call this CHEMICAL BIOND ENERGY
                               the energy of cells is stored in the COVALENT BONDS of their molecules.

                  
HOMEOSTASIS ...most of cell's energy is needed to maintain a steady state.
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 BIOENERGETICS - is study of energy transformations (changes) in Biological systems is based on

       EQUILIBRIUM THERMODYNAMICS
...

                   1st LAW = Conservation of Energy... energy is a constant;
                                   energy can not be created nor destroyed, only transformed
                                           ... experimental caloric data says this LAW is true
                                               
 combustion of glucose releases heat = 686 kilocalories/mole
  

                   2nd LAW = Energy transformations reduce the order of the universe
                                     entropy is directional --- > toward equilibrium (toward maximum disorder)
                                           ... ENTROPY = amount of disorder in a system -
ENTROPY*
  

       The Rules of Universe are simple :
                   Cities crumble, stars go Supernova, & we're all dying... (equilibrium...izing)
                                             law of ENTROPY says... Degree of disorder of the Universe
                                                     (its randomness - its entropy) CAN ONLY INCREASE.
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  Cells obey Laws of Chemistry & Physics


         yet CELLS.....  WOW !   .......become more highly ORDERED as they divide & grow...
               fertilized egg ---> wing of bird,  a spider's web,  the human eye,  dividing cells,  etc...
                                 from fertilized egg cell... which  Feeds, Grows & Differentiates  =  HOW?

               for part of a system to become more ordered - lose entropy - (such as a cell),
                                             its surroundings must become more disordered - gain entropy -

FOODs (light & covalent bond energy)

Next.gif (275 bytes)

cell reactions give increased order within cell

Bkarrow.gif (279 bytes)

with release of HEAT

flag22.gif (924 bytes)                  HEAT (most disordered form of energy) = max entropy



 

 

 




 
 ENERGY IN ----> CELL STRUCTURE ----> ENERGY OUT

                How do we measure energy changes in cells...

        Josiah Gibbs (1880's) FREE ENERGY Equation      DG      =     DH        -   T DS
                                                                           free energy     enthalpy         entropy

         DG is measure of amount energy change (D) in a system that is able to do Work...
         DG is a numerical measure of how far a chemical reaction is from equilibrium...
                     µ   Disorder Increases (Entropy Increases)... when useful energy,
                                          that which could be used to do work, is dissipated as heat...
   
                 cells are ISOTHERMAL  -  (-2o to 37o)  - thus DH = 0 above
                                   Enthalpy may be thought of as
heat content of a system
                                   cells function within a very narrow temp range [23o-37oC],
                                   and thus
DH is negligible in the equation.
   
                thus
DG can PREDICT...    the Direction of Cellular Reactions...
                                  TOWARD EQUILIBRIUM...     toward Maximum ENTROPY
flag23.gif (924 bytes)                                                                             toward a release of free energy
 
 
 
 
 
 
       


 
 CHEMICAL REACTON    A <---> B     Which Way is toward more Disorder?
     

               
   DG  = DG0 RT ln  [p]/[r]               a derivation of Gibbs Free Energy equation
  

      change in free energy content of a reaction...depends upon:
            1.  energy is stored in molecule's covalent bonds
            2. temperature is negligible... i.e., cells are isothermal, thus...
                     

                   
DG       =    actual free energy at any time in a reaction
                   
DGo'    =    standard free energy   [free energy change under standard conditions]
                    R          =    gas constant ( 2 x 10-3 Kc/mol)
                    T          =    absolute temp (273
0K  + 0C)
                    ln          =    natural log (conversion to log10 = 2.303)
           

            3. 
at equilibrium by definition    DG = 0   and  we call   [p]/[r]  =  Keq
    
flag24.gif (925 bytes)                                                                                                                                                                equilibrium constant
    

         

 

 

 

 

  
  
Free Energy Equation... 

    ΔG  =   ΔG0'   +   RT  ln [P]/[R]
     
       @ equilibrium  ΔG  =  0                     0  =   ΔG0'   +   RT  ln [P]/[R]
                       .... thus  rearranging     
ΔG0'  =  -RT ln [P]/[R]                 

       @ equilibrium         [P] / [R]   =   Keq

  &  @ 250C ... -RT ln Keq =  -(2.0) (298) (2.303) lg10 Keq  =   -[1372] lg10 Keq

                                  thus..........   ΔG0'  =  - [1372]   lg10 Keq  

                                                                                                   R  =  gas constant ( 2 x 10-3 Kc/mol)
                                                                                                   T  =  absolute temp (273
0K + 0C)
                                                                                            ln =  natural log (conversion to log
10 = 2.303)

 

 

 

 

  
 
  when we solved above equation for DGo'  we could see relationship* of Keq to DGo’ 
  

  The difference between
   
ΔG   and    ΔG0'
   
    ΔG0' is a fixed value under idealized conditions for a given reaction &  indicates
                     in which direction that reaction will proceed at standard conditions. table

                            standard conditions do not exist within a cell, but ΔG0' may be
                            useful to predict the direction of a reaction at a specific given time.

        
ΔG   is determined by the concentrations present at a given time and
                  is a measure of how far a reaction is from equilibrium at that time.
  
                            Cell metabolism is essentially a non-equilibrium condition.

         Metabolism works by changing the relative concentrations of reactants
                       and products to favor the progress of non-favored catalytic reactions.  
     

 

 

 

 

 

 

 

 

 
    CHEMICAL REACTIONS 
 
A <----> B      Which Way & Why?

    EXERGONIC REACTION - is one which releases free energy    [ -
DG ]
        Product (B)  <<< energy  REACTANT  (A)    [energy stored in covalent bonds]
            ex:    burning wood (cellulose)
                             glucose polymer...  potential energy.
                             breaks bonds, release heat & light ---> CO2 & H2O    fig 9.5*
                     cell respiration - cellular burning of glucose molecules.
                             slower,   multi-step process that captures & releases
                                          some energy... as ATP

    ENDERGONIC REACTION - requires input of energy for  A --> B
        Product (B) >>>  energy than   REACTANT (A)                 [  +
DG  ]
            ex:      photosynthesis (autotrophy)
                      glucose is made from  CO2
 +  H2O --light-->  C6H12O6
                                                      energy poor      vs.       energy rich
   flag25.gif (889 bytes) 

 

 

 

 

 

 
 CELL METABOLISM is then a mix of...

           Exergonic  &  Endergonic  reactions that occur inside of cells...
                                                                                                     Concept Activities - chapter 8.3 - Chemical Reactions & ATP.

   How does Cell Metabolism really work energetically?
              for RX's which share one or more intermediates (a pathway)...   [ A-->B-->C-->D ]
              the overall free energy change (
DG) is the sum of indiv DG's
                                                        DGo'
            Glu + Fruc     --->    Sucrose                                 + 5.5 Kc/m
                     ATP*     --->    ADP + P                                 - 7.3 Kc/m
  
            Glu + ATP     --->     G-1-P + Fruc ----> Suc + P      - 1.8Kc/m

                     COUPLED REACTIONS - involves say... the linking of the hydrolysis of ATP
                                  (a favored rx)  to a thermodynamically unfavored reaction,
                                   thereby creating biological order (greater molecular structure).
                     
   flag26.gif (901 bytes)                                    another ex:    synthesis of glutamine*

 

 

 

 
WHY ATP ? ? ?   shouldn't any nucleotide work?
    ... the ENERGY MOLECULE of CELLS is  ATP
             over the period of evolution,  cells favored enzymes that
             bound ATP & used its hydrolysis to drive endergonic reactions.
ATP

   adenosine triphosphate figure 6.8  * its structure is its source of energy
   1. electrostatic repulsion  2. resonance  3. sphere of hydration   Concept Activities - chapter 8.3 - The Structure of ATP*
   HYDROLYSIS of ATP  ATP    DG0'     =      -7.3 Kc/m     [ exergonic by some -7,300 cal/mol ]

         How ATP works -    phosphorylation*   &    metabolic ATP coupling*
                                                               
Concept Activities - chapter 8.3 - Chemical Reactions & ATP.

    flag25.gif (889 bytes)      next Lecture:    How cells make ATP*                                 a paradigmkey concepts*

    copyright c2010     Last update - Friday, March 05, 2010
        Charles Mallery,    Biology 150, Department of Biology,   University of Miami,  Coral Gables, FL 33124
                        
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