The Design of Metabolism:
                                        key concepts
                                                 How Cells Transform Energy...
                                 or  How Biological Order Comes About,
...  (Gk -metabole - meaning change)
                                  is mostly the catalytic reactions (run by
enzymes) in that occur in cells,
                               & commonly via metabolic pathways [A --> B --> C --> D --> E]

             Two broad descriptions of cellular metabolic reactions
* are  Exergonic/Endergonic
                                 also, metabolic reactions are often described as...
     ANABOLIC...    Biosynthetic reactions:            often visualized in...   photosynthesis*
             - energetically un-favored reactions coupled with favored reactions
             1)   PHOTOSYNTHESIS -
reduction of CO2 to CH2O  &  synthesis of ATP & NADPH
CATABOLIC...  Chemical oxidation
of food stuffs via 
Cell Respiration* 
             1)   DIGERSTION of POLYMERS (carbs
often to glucose) via hydrolysis reactions 

GLYCO-LYSIS   converts glucose ---> pyruvate    [anaerobic splitting of glucose]

  KREBS CYCLE    aerobic oxidation of Acetyl-CoA  --->  CO2 + H2O ---> NADH
  ELECTRON TRANSFER      --->    NADH + O2  ---->  H2O +  H+gradient
ATP SYNTHASE   --->    uses H+
gradient to phosphorylate P + ADP ---> ATP
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ENERGY TRANSFORMATION...   is a key to understanding cellular metabolism. 
             It is the change from one type of energy to another type while making
             something happen, which often also releases useless energy as heat.
   Energy concept:
*    often defined as capacity or ability to do work and
                                  work is a measurement of change in a system over time.
*: POTENTIAL - stored energy; capacity to do work (eventually);
KINETIC       - energy of motion 
CHEMICAL  - electron bond energy
                ELECTROMAGNETIC  - photon light energy from the Sun
HEAT - assoc with movement of molecules in a body of matter;
                             most random form of energy (wasted).
                Examples:         general:  heat,  light,  sound,  mechanical.
                                    biological:  synthetic,  osmotic,  motion.
  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 BOND ENERGY because 
     the energy in cells is stored in the COVALENT BONDS of their molecules.
                    most cellular energy is needed to maintain...  HOMEOSTASIS*
flag19.gif (911 bytes)               a steady state condition that transforms energy
                             and keeps cell's away from equilibrium.








      is study of energy transformations (changes)
in Biological Systems & is based upon...

       EQUILIBRIUM THERMODYNAMICS... is the systematic study of transformations of matter
                          and energy in systems in terms of a concept called thermodynamic equilibrium,
                          where the word equilibrium implies a state of balance
(thermal, mechanical,
                          and chemical equilibrium) that does not change with time and space.

         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 a true hypothesis.

  Calorimetry* of glucose releases heat  =  -686 Kilocalories/mole (180 amu).
                           In cells oxidation of glucose
yields free energy: ΔG°′  =  - 686 Kcal/mol.
                              To capture this free energy in a usable form cells employ a
                           series of metabolic steps coupled to the synthesis of ATP.


         2nd LAW = Energy transformations favor reducing the order of the universe:
          thus entropy = is a measure of disorder in a system -
               Entropy is directional ---> toward equilibrium (toward maximum disorder)
                                  and may define time - a change of one observed status to another status
       The Rules of Universe and equilibrium thermodynamics are simple :
                   the natural tendency is for disorder to increase spontaneously.

                   Cities crumble, stars go Supernova, & we're all equilibrizing (dying...)
Law of
ENTROPY says... Degree of disorder of the Universe
                                       (its randomness - its entropy) CAN ONLY INCREASE.
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Do Cells obey Laws of Chemistry, Physics, & Thermodynamics?       
  CELLS appear not to...
  WOW !   ...they become more highly ORDERED [grow & divide].
Fertilized egg ---> 
dividing cells, wing of bird,  a spider's web,  the human eye,   
        all from a fertilized egg cell... which 
Grows & Differentiates. we get more order:  HOW?


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

                              Cells exchange Materials & Energy with their surroundings...

FOODs (light & covalent bond energy)

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cell reactions give increased order via energy transformations

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but with release of HEAT

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





How do we
measure the energy changes of metabolism and reactions in cells...

   Josiah Gibbs (Yale 1880's) devised applications of thermodynamics to chemical reactions...
ΔG      =     ΔH        -   T ΔS
free energy     enthalpy       entropy

         ΔG is measure of change (Δ) in amount energy in a system that is ABLE TO SOME WORK...
 ΔG is a numerical measure of how far a chemical reaction is from equilibrium...
                        Entropy Increases (Disorder Increases)... when useful energy,
                                that which could be used to do work, is dissipated as heat...
 ΔH - enthalpy is internal heat, often measured as heat released in a reaction.
                  but, cells are ISOTHERMAL(-2o to 80oC many @ 37oC) - thus ΔH above 0
Enthalpy may be thought of as
heat content of a system.
                                   Cells function within a very narrow temp range [23o-37oC],
                                   and thus, biologically
ΔH is negligible in the equation;
ΔG in cells then is  =  T x ΔS  the entropy of the system; its degree of disorder.
ΔG can PREDICT...    the Direction of Cellular Reactions... TOWARD EQUILIBRIUM...     
                            Toward Maximum ENTROPY   &   Toward a Release of Free Energy.
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 in a BIOCHEMICAL REACTON    A <---> B     Which Way is toward more Disorder?

    We need to be able to
measure the change in Entropy [
ΔS] of a reaction...  but how?
A derivation of Gibbs Free Energy [ ΔG = ΔH - T ΔS ] equation can help here:

ΔG  = ΔG0 RT ln  [p]/[r]   

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

ΔG        =    actual free energy at any time during course of a reaction
ΔGo'    =    standard free energy... free energy change under specific conditions]
                                                when 1 mole of substance is formed at
  250C, 1 atm, etc...
                                                a measure of how far a reaction is from equilibrium.

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

at equilibrium by definition   ΔG = 0   & we can call ratio of   [p]/[r]  =  Keq
                                                                                               equilibrium constant
flag24.gif (925 bytes)            thus...









   Let's solve the Free Energy Equation for Standard Free Energy  
ΔG0' ... 

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

       @ equilibrium  [P] / [R]  is referred to as the Keqthe Equilibrium Constant

  &   @ 250C  ... -RT ln Keq        =  - (2.0) (298) (2.303) lg10 Keq  =   -[1372] lg10Keq

                       ... thus     ΔG0'     =  - [1372]  lg10Keq      
R  =  gas constant ( 2 x 10-3 Kc/mol)
                                                                                                                             T  =  absolute temp (273
0K + 0C)
                                                                                                                             ln =  natural log (conversion to log
10 =
2.303)   .
             So now we can measure
ΔS [entropy] by observing the ratio of the
                     CONCENTRATIONS of reactants & products

   by solving the above equation for ΔGo'  we can see the relationship* of Keq to ΔGo'









The difference between   
ΔG  (actual free energy)  and    ΔG0'  (standard free energy)
  ΔG0   is a fixed value under idealized conditions for a given reaction conditions,
[1 mole reactants / 250C / 1 atmosphere] and indicates in which direction
                   that reaction is likely to proceed toward equilibrium. o

                   Cells often employ hydrolytic reactions to add energy to unfavorable reactions.
                           phosphoryl hydrolysis
*     and      table of Phosphoryl hydrolysis*

                   Standard conditions do not exist within a cell, but ΔG0' is useful to
predict the likely direction of a specific reaction (exergonic or endergonic).

ΔG    is determined by the concentrations present at any given time during a reaction
                   and is a measure of how far a reaction is from equilibrium at that time.

Cell metabolism (Life) is essentially a non-equilibrium condition.

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









A <----> B      Which Way & Why?

    EXERGONIC REACTION - is one which releases free energy    [ -
ΔG ]
        Product (B)  <<< energy  REACTANT (A)   [energy stored in covalent bonds is lost]
            ex:    burning wood (cellulose)
                             glucose polymer =  chemical potential energy.
                             breaks bonds, release heat & light ---> CO2 & H2O   
fig 9.4*
                     cell respiration - cellular burning of glucose molecules.
                                                slower,   multi-step process that captures
                                                            & conserves some energy... as ATP

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

       Exergonic vs. Endergonic summary            
---->   LIFE and EQUILIBRIUM*...        
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   CELLULAR METABOLIC REACTIONS are then a mix of...

          Exergonic  &  Endergonic  reactions that occur inside of cells...
                How does Cell Metabolism really work energetically within cells?
                        for RX's which share one or more intermediates (a pathway)...
                                                 [ A --> B --> C --> D  = 
-ΔG ]
                the overall free energy change (ΔG) is the sum of indiv ΔG's

    Glu + Fruc-6P  --->    Sucrose                                    + 5.5 Kc/m   =  not favored
ATP*      --->    ADP + P                                    - 7.3 Kc/m   =  favored

    Glu + UTP        --->    UDP-G + Fruc-6P  -->  Suc-6P + UDP  - 1.8Kc/m  (the reaction
* - often involve... the linking of the hydrolysis of ATP
favored rx)  to a thermodynamically unfavored reaction,
creating biological order (greater molecular structure).


   flag26.gif (901 bytes)          another ex:    synthesis of glutamine*









 Why is ATP the "molecular currency" of cell energy transfers?    

  ... the ENERGY MOLECULE of CELLS is 
          over the period of evolution,  cells
favored enzymes that 
ATP & used its hydrolysis to drive endergonic rxs?
but, couldn't any nucleotide work?
        Was there a 1st ATP?*  

adenosine triphosphate
* -  its structure* is its source of energy...
   1. electrostatic repulsion  2. resonance  3. sphere of hydration... 
     HYDROLYSIS of ATP  ATP       ΔG0' = -7.3 Kc/m     [ exergonic by some -7,300 cal/mol ]


How cellular ATP works  -
*  &    an ATP cycle*

      key Concepts*     
        next Lecture:                        How do cells make ATP* 

      copyright c2024     Last update -  March 2024
        Charles Mallery,    Biology 150, Department of Biology,   U. of Miami,  Coral Gables, FL 33124