The Design of Metabolism...
         Cellular Energetics & Chemical Equilibrium

Biological Order  and  Cell Energy Transformations
CELLS Do OBEY LAWS of CHEMISTRY & PHYSICS

   
ENERGY TRANSFORMATION within CELLS is ABILITY TO DO WORK...
   

  
2 kinds of traditional energy:
            1.  Potential Energy... stored energy, due to mass in position
       
2.  Kinetic Energy (energy of movement)
          
     ex: heat (thermal) energy which flows from higher heat
                              or greater molecular motion to lower heat content;
                    
radiant energy kinetic energy of photons (light);
                              when molecules absorb light radiant --> thermal
                                      chlorophyll  --
light--> ATP in photosynthesis
                    
mechanical energy - push/pull of cytoskeletal filaments
                    
electrical energy - energy of moving electrons

                                                              pages 54-60

 

 

 

 

 

 

    
    
 

  

ENERGY in cells is housed
               in a molecules CHEMICAL BONDS
                             
covalent bonds

   

   cells possess "Chemical Potential Energy"

   energy also occurs in such cellular forms as:
  

     chemical concentrations gradients
             across membranes
             can diffuse from  [higher]  to  [lower]
     electrical gradients (potential differences)
             across membranes
             a separation of charge
             as much as 200,000 volts per cm

 
  

 

 

 

 

 
 
THERMODYNAMICS: the SCIENCE of ENERGY TRANSFORMATIONS
   1st Law of Thermodynamics... Energy can neither be created nor destroyed,
                   but is convertible.    
nuclear blast - mass of U235 --> heat/light
                                                   photosynthesis --> sunlight into glucose bonds
                                                   muscle --> hydrolysis of ATP in contractions
        all forms of energy are inter-convertible thus all are expressed in same
        units of measure
Joule, but biologists use more common calorie                 [heat é 1gm 1oC]
                                                  1 Kcal = 1,000 cal  =  4.184 Joule                  [1 cal = 4.184 J]

 

 
    2nd Law of Thermodynamics…   ENTROPY
   
                     is commonly referred to as a measure of degree of order of the Universe,
   
                     and thus its randomness (Entropy = disorder) CAN ONLY INCREASE 

                          The Rules of the Universe are simple:
            
                 Cities crumble, Stars go Supernova, and we are all equlibrium...izing (dying)
                                   
 Entropy* is maximum disorder.....  "heat"
                                                 Events in the Universe have a direction
---> MAX ENTROPY
  

 

 

 

 

 

 
  
According to Laws of Thermodynamics, biological systems should proceed
                                                           with a loss of energy toward a greater degree of disorder

       Yet,  WOW! …   
Cells are highly ordered...
                      and life appears to go from more simple to more complex

                                                             wings of a bird, human eye, spider’s web
                                                             and all cells - feed, grow, and differentiate

  

 
  HOW...    in light of the 2nd law of thermodynamics ?                 

    FOOD (light energy & covalent bond energy in total surroundings)

                        
                                                                 HEAT = overall increased entropy

                                Entropy must increase (heat); yet disorder within one part of Universe
                        can decrease at the greater expense of the Total Surroundings. 

 

 

 

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

    What we need to be able to do is
measure Energy in systems, esp. energy able to do work 
         
Willard Gibbs (1839-1903) applied the principles of Thermodynamics to chemical systems
                          to determine the energy content and changes within a chemical reaction
                          and derived the...

    
        FREE ENERGY EQUATIONS        DG      =    DH      -   T DS                  *
        
                                                free energy      enthalpy     entropy
   

            
DG is a numerical measure of how far a reaction is from equilibrium
             DG is measure amount energy in system able to do work (to stay away from equilibrium)...                           Disorder increases (thus entropy increases) when useful energy,
                                   that which could be used to do work,
is dissipated as heat...
              
          biological systems are are ISOTHERMAL, e.g., held at constant temp/pressure
                                                
(4o to
@ 45o )  and   thus in biological systems DH @ 0

  

 

 

 

  

    What Gibbs showed was that  "cell chemical systems change so that Free Energy is minimized"

             thus,  DG can PREDICT..... the Direction of Cellular Reactions......
                                                      TOWARD EQUILIBRIUM  and  to Maximum ENTROPY
 

             Any natural process occurs spontaneously, if and only if,
                                     the associated change in G for the system is negative (ΔG < 0).
             when -
DG is negative a reaction is spontaneous, R --> P, & there is a increase in entropy

             Likewise, a system reaches equilibrium when the associated change in G
                       for the system is zero (ΔG = 0),

             and no spontaneous process can occur, if the change in G is positive (ΔG > 0).
  
  

 

 

 

 
 
CHEMICAL REACTION   
A <---> B     Which Way?
          
                          
DG  = DG0  +  R T ln [ p]/[ r]
  

    change in free energy content of a reaction...depends upon:
        1.  energy is stored in molecule's covalent bonds
        2. remember, temperature is negligible... cells are isothermal, i.e.,                      
                   
D       =    actual free energy
                   
DGo'     =    standard free energy [change under standard conditions: 25oC (298 K),
                                                                              1 atmosphere, reactants @ 1 [M], & pH 7.0
]
                    R          =    gas constant ( 1.987 x 10-3 Kc/mol)
                    T          =    absolute temp (273oK);    thus @ 25oC  =  298oK
                    ln          =    natural log (conversion to log10 = 2.303)

            but, 
at equilibrium   DG = 0     and we'll say the     [p]/[r] = Keq
 
              if we solve above equation for
DGo'  we can see the relationship of Keq to DGo’ 
     

 

 

 

 

 
   
Free Energy Equation...              
                            
ΔG  =   ΔG0   +   RT  ln   [P]    
                                                              [R]

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

       @ equilibrium         [P]    =   Keq
                                  
    [R]

       @ 250C ... -RT ln Keq =  -(2.0) (298) (2.303) lg10 Keq  =   -[1364] lg10 Keq

                                     thus..........   ΔG0   =  - [1364]  lg10 Keq  
   

 

 

 

 

   
  The difference between...
        
   DG     and   DG0 
    
              DG      is determined by the concentrations present at that time,
                             & is a measure of how far a reaction is from equilibrium then.
                             Cell metabolism is essentially a non-equilibrium condition.
  
    
        
DG0  is a fixed value for a given reaction under standard conditions of 250C,
                             1 atm, pH 7.0, and [1M initial reactants & products], & indicates in which
                             direction a reaction will proceed under standard conditions, i.e., is it 
+/-.

                                 
  standard conditions do not exist within a cell, thus
DG must be
                                   used to predict the direction of a cellular reaction at a given time.

  

              
µ   Metabolism works by changing the relative concentrations of reactants
                     and products to favor the progress of unfavored reactions to completion.
 
  

 

 

 

 

  
 Relationship between  Keq  &  DG0         DG0   =  - [1364]  lg10 Keq

products

reactants

Keq

lg10

DG0 cal/mole
 
[ lg10 x -1364 ]

 

 

 

[R] > [P]


1/1000

 
.001

10-3

 
-3

 
+ 4092

1/100


.01

10-2

-2

 
+ 2728


1/10

.1

10-1

 
-1


+ 1364

 

 
1/1

1.0

0

0

0


[R] = [P]

 

10/1

10

10+1

+1

- 1364

 

[P] > [R]

100/1

100

10+2

+2

- 2728

1000/1

1000

10+3

+3

- 4092

  

 

 

 

 

 

 

 

                          rx #5 pg 482

      Which way this reaction goes is dependent upon existing concentrations?
              DG0’     @ cell [equilibrium]       the    Keq  of   DHAP/G3P =  22.4
        
DG0’     =    - [1364]  lg10 22.4   =   - [1364]  (1.35)   =  - 1,842 cal/mole
   
   D =  DG0’   +   RT  ln   [P] / [R]            but, when DHAP = 0.001M    &   G3P = 0.1M
  

        
=  -1842 c/m   +  (-1364) (lg10 0.01)    =  (-1842) + (-1364)(-2) =  + 886 cal/mole

         Thus under standard condition the reaction is favored from G3P toward DHAP (-DG),
         but under a specific cellular condition, where the ratio of reactant & products is changed,
         the reaction may not be favored, and will go in other direction from DHAP to G3P..
   

         This is what happens in glycolysis* , but the pathway shifts ratios and pulls it to G3P.
  

 
 
 
 
 
 
 
 
  CHEMICAL REACTIONS    A <----> B    Which way depends on the free energy...
  

    EXERGONIC REACTION - is one which releases free energy
        Product  [B  <<< energy     REACTANT   [A]    [stored in covalent bonds]
            ex:    burning wood (cellulose)
                               glucose monomers  =  potential energy
                               breaks bonds, release heat & light ---> CO2 & H2O
                     cell respiration -  (heterotrophy) -  cellular burning of glucose
                               slower,   multi-step process to capture & release
                                            energy.... as ATP
                                                                                                                fig 2.29
*
    ENDERGONIC REACTION -   requires input of energy for   A --> B
        PRODUCT   [B]   >>>energy     Reactant   [A]
            ex:    photosynthesis -  (autotrophy)
                               glucose made from CO2 + H2O  --light--->   C6H12O6
                                                energy poor       vs.              energy rich


  
 

 

 

 

 Many biological systems lead to an increase in order (decrease in entropy ( DS < 0)?
            How does Metabolism create more order in chemical reactions?

  COUPLED REACTIONS - involves say... the linking of the hydrolysis of ATP
                      (a favored reaction)  to a thermodynamically unfavored reaction,
                       thereby creating some biological order (greater molecular structure).
    

               if
DG for the reaction  B + C  -->  D  is +,
                         but if it is less than the
DG of ATP hydrolysis,
                         then the reaction may be driven to completion by coupling.
                                                                                 synthesis of glutamine*
  

                most cells use ATP hydrolysis energy and couple it to processes as:
                        conformational changes in enzyme, as kinases, which phosphorylate
                        proteins converting then from inactive to active (& vice versa);
      

                        energy gained in the stressed conformation is released,
                        when the protein relaxes.

  

 

 

 

 

 

 

         
 Design of Metabolism:
    metabolism is run via  enzyme catalyzed metabolic pathways*
 
                                          which can get very complex...    ecb fig 3.2 & Kegg fig*   
   
   
    2 Categories of metabolic reactions:

         
Anabolic  -   biosynthesis in autotrophs
  
                          coupling of reactions that are energetically unfavorable
                               with reactions that are energetically
favored 
                   
           done by linking ATP hydrolysis* (favored) to reactions 

   

         Catabolic
  -  cell respiration in heterotrophs                                        
     
                                oxidation (removal) of e-’s from foodstuffs  
                              
3 steps:            1.  Digestion of polymers (foods) into monomers
                                           
          2.  GLYCO-LYSIS ---> AcoA      splits sugar monomers
                                
                      3.  Oxidation of AcoA ---> CO 2 + NADH ---> H 2
                                                                           ADP + P ---> ATP

  

            µ    linking pathways together (not favored), creates new biological order  [ecb 3.3]  
 
 
    
     


 

        
   

 

 

  

 
Design of Metabolism...
   or how biological order comes about...
                        
via a balance of Endergonic & Exergonic reactions.
   

   

Autotrophs  endergonic
      light energy...   is converted into covalent chemical bond energy
                 e-

 

  CO2 oxidized form
           
 
H2O        ATP + NADPH

        more energetically stable
   

                  CH2O          less energetically stable
                 H+   reduced form
 
Heterotrophs:   exergonic
      food stuffs      [CH2O]n       CO2 + H2O + ATP
                                            NAD       NADH 
  
                    Balance between photosynthesis & respiration --> ecb 3.10

                 Key Cell energy intermediates- NADH & NADPH, FAD, & ATP

   

 

 

 

 

 
 
 Design of metabolism... 
 

      
OXIDATION / REDUCTION - Redox Reactions are a major energy capture mechanism  
             
e-  &/or  H+   transferred between oxidized & reduced forms of e- carrier coenzymes

AH         A   +   e-  +     H+

           oxidation    -   removal of e-  from substrate             oxidation states
reduction   -   gaining of  e-  (& often a proton, H+)

     NAD +     respiration     NADH
  6O2    +    C6H12O6                6CO2    +    6H2O  
                              NADP+   photosynthesis  NADPH

 

 

 
 

 KEY  METABOLIC  REACTIONS:    6 major categories of bio-chemical reactivity
                    
Bio-chemical reactivity is bond breaking & reforming
                     these are violent events inside cells, carefully controlled by
ENZYMES
          1. functional group transfers          glu + ATP  <-->  G6P  +  ADP
                                 transferases
          2. redox reaction (oxidation/reduction)   PGAld + NAD+  <-->  1,3di-PGA  +  NADH
                                 oxidoreductases (dehydrogenases)
          3. rearrangement (isomerizations)   glucose-6P  <-->  fructose-6P
                                 isomerases
          4. C-C breaking or re-formation     fruc1-6bP   <-->   DHAP  +  3PGAld
                                 lyases
          5. Condensations         protein(n)  +   aa 1   <-->   protein(n+1)  +  H 2O
                                 transferase
          6. Hydrolysis             glu-glu(n)   +   H 2<-->   glu-glu(n-1)
                                 hydroylases
              the work horses of metabolism (life) are the enzymes...