Molecules of Living Systems                  
 
                         the chemical properties of the living state

The structure of biological molecules and how their shape determines the roles
 they play in the complex chemical processes of life.
          Even the most complicated biological molecules can be divided 
          into smaller and smaller
functional groups.       

  REDUCTIONISM...

    Text description - Molecules of Living Systems*
 
                  Some Web Resources that give 3-D shapes of Biomolecules
                                          a web site for review of the Molecules of Life  mwk
              
                                                         chapter 2 pg 31-54

 

 

 

 

 

 

 

 The chemicals of life... 
 
ELEMENTAL CHEMISTRY
     
-  elements are substances composed of atoms all with identical number of protons
  
   -  can’t be reduced to simpler substances by normal chemical means
      -
 only 30  of  92  elements  COMMONLY  OCCUR  IN  LIVING  SYSTEMS... 
      - 
and 
99% of LIVING MATTER is made of...     C H O P S N  
                         all have
low atomic numbers,
                                 table of valance electrons
                         & are easily reactive &
form covalent bonds*      covalent bond figure 

 Molecular composition of cells...
Water (H2O)        70 %
Inorganic ions (Na, K, Cl, PO4) 1 %
Small molecules (aa’s, sugar, nucleotides)  5 %
Macromolecules (protein, n.a., etc) 24 %
                                            chemical composition of bacteria*        -->  JMM

                                               

                                                           

 

 

 

 

  Biomolecules, Weak Forces, & Design of Metabolism
  

 
The properties of chemcials that are esssential for ALL CELLULAR PROCESSES and
                    may have lead to the EMERGENT PROPERTIES of molecular systems (akin to life)       

   

 
BIOMOLECULES... mostly carbon compounds are found in living systems…
  

    
WHY Carbon
?              (carbon skeletons)*
  

        
- easily forms 4 covalent bonds… thus makes many small biomolecules
           
atom's electronegativity is able to attract electrons from other atoms:
              nonpolar covalent bond:
equal electronegaivity/equal sharing of e-'s  [C-C, C-H]
              polar covalent bond:
unequal electronegativity results in unequal charge distribution
                                    
within an electrically neutral molecule  [water - fig 2.5*].

  

    
    - allows 3-D shapes that may evoke biological activity based upon conformation
 

    
   
- carbon favors great chemical reactivity
  

 
     

 

 

 

 


     
   - Carbon covalents interacts with common chemical functional groups*

                   Functional Groups:
                      
 groups of atoms, acting as a unit, that give organic molecules
                        their
physical properties, chemical reactivity, & solubility in aqueous solutions.

                                 In bio-molecular chemistry, the concept of functional groups is useful, 
                                 as a basis for classification of large numbers of compounds according
                                 to their chemical properties and reactivity. 
 
               most functional groups possess electronegative atoms on C's      [ C O, N, P, S ]
               key bonds are :    esters   C-O-C*     &     amines & amides   -C-N-*
               most are ionizable at physiological   ( pH 6.6 to 7.4)  read pages 47-49* 
                         Topic test - Molecules of Life
                    Consequences of substitution with a functional group*

                                                         
                

 

 

 Let's look at small Biomolecules   made via Chemical Bonds & Functional Groups
               
                                   
  Major groups of small biomolecules...
   the monomers - 
mcb fig 2.13
* - make polymers
                   

      
a.   SUGARS - compounds with repeat formula of...      
[CH 2O] n      
                aldoses vs. ketoses
*rings*,   a 
& ß-links*,  
isomers: glucose vs. galactose*
Text description - the BIOMOLECULES of Living Systems*             glucose + glucose = mono-,   disaccsaccharides*,  tri-,  polysaccharides*
           
& long chain polymers of monosaccharides                                                      


    

    
      b.   FATTY ACIDS - 
saturated FA* 
vs unsaturated*fatty acids*       [Table 2.4*] 
                  
  form  triacylglycerols* = lipid - 3 chain hydrocarbons*   3 lipids  &  animal fats
        
                                                                                                                                                                                               
*                  and phospholipids* of membranes (mcb fig 2.20*)                        
                 
      easily self-assembly into aggregates*:   soap micelles   &   bilayers*  &  fluidity*
                

        
         also  steroid & cholesterols* (4-ring skeleton) are lipids because they're insoluble
 
                       in membranes (mcb fig 1.13)*         mcb5e fig 18.6 derivatives      end 6

 

 

 

 

      

 

  
   
        c.   NUCLEOTIDES           parts*                    &  nomenclature*
                 
nitrogen containing "ring" compounds…   
                       a
nitrogenous-base
(fig 2.17) linked to a 5-carbon sugar (fig 2.16
*) & a PO4
                       pyrimidines = C, T, U  or  purines = A, G      (ribose & deoxyribose)
                       single rings                 double rings  

                                             nucleotides form the energy rich compounds of cells
                                         (as
ATP* & GMP), as well as the
nucleic acids.

                                          
all are acidic for PO4 group releases H+ leaving an anion  
Text description - Amino Acids and Nucleotides*                                                                                                      Tpoic Test - Amino acids and nucleotides
        d.   AMINO ACIDS         Fig 2.21*         (pics)           peptide bond*  
             hundreds known, but only 20 common in proteins of cell.
                    
once established in the "primordial cell", 
                     certain small biomolecules,  as covalent themes, 
                     seem to have been preserved throughout evolution 

                                                   (i.e., they were favored energetically)

      

        
 

                                                                                            

 

 

    

Biological Activity   &  
                                  the Shapes of Biomolecules
 
Structural Chemistry:  orientation of covalent bonds in space.
   molecular configuration
results in specific bond angles and molecular geometry
  
      methane              CH4          109.5o   - a tetrahedron      with free rotation
      formaldehyde    H2C=O       120o      - same plane          with no free rotation

fig 2.3*

   
         one key to shape is the ASSYMETRIC CARBON...
            a carbon atom bound to 4 dissimilar atoms in a nonplanar configuration (tetrathedron)
                    results in 2 different spatial orientations --> producing CHIRAL molecules...
                    ones that are mirror images of each other (i.e., optical or stereoisomers)

 
 

 

 

 

 

 

 
   
ENANTIOMERS*  molecules  that are non-superimposable mirror images of one another
  

       called
Stereoisomers...
    the two molecules are not equivalent or identical, and
                                                 have
2 molecular orientations  or mirror images

               an optically active,
CHIRAL*, is not superimposable on its mirror image
                                                                                                                       
chiral animation

               stereoisomers may have mostly
identical chemical properties
                     but often rotate plane of
polarized light via different angles.
                            
LEVOROTARY
* (L) - rotates light left    (- negative optical rotation)
                         
   DEXTRORTATORY (D) - rotates light
right  (+ positive optical rotation)

                and likely have different BIOLOGICAL ACTIVITY...
                            
             Parkinson's Disease  &  dihydroxyphenylalanine = L-DOPA   figure*
                                                                                                               "awakenings"
    

 

 

 

 
  Biological activity... is catalytic ability of molecules to do work 
       
          There are 2 properties of biomolecules,  which contribute to a molecules 
                                       
unique FITNESS for Biological Activity & the Living State                 Text description - Shape and Form of Biomolecules*

   A.   CONFIGURATION: spatial arrangement of atoms in molecules about bonds...
                                        
     configuration can’t be inter-converted w/o breaking bonds
   

          covalent examples of configurations:

       

                  isomers...
 based upon covalent bond configurations [glu vs. gal]*
                                 
each has different chemcial properties
   

            
                      and those due especially to COVALENT DOUBLE BOND*
   

                
 isomers... built upon double bonds        C=C                  Cis = Trans*
                                  fix atoms above & below plane of molecule &
                                  restricts free rotation, thereby fixing 3D shape
in space.
                                                     maleic (
cis)
      vs.     fumaric (trans
                              11-cis-retinal     vs.     11- trans-retinal 

 

 

 

 

 

 

 
Biological Activity   & the   Shape of Biomolecules   continued...

B. CONFORMATION  [or shape] - surface outline or contour
      3-D orientation of chemical groups that are free 
      to assume different positions in space without breaking any bonds 
      - do primarily to...
      
    FREE ROTATION of atoms about a single chemical bond 
           WEAK NON-COVALENT FORCES hold atoms in spatial arrays
3D-conformation
      - consequences of conformations...
            different isomeric shapes (forms) of molecules can exist,
           
only one of which may be biologically active  (others aren't) 
  
    
        ENZYMES can distinguish between
biologically active forms (isomers) 
                                      based upon the "
SHAPE" of that isomer
                Topic Test - Shape in Biomolecules              

    

  

 

 

 

 

 due to                   Weak Molecular Forces of Life...

IONIC bonds*  attraction between cation (+) & anion (-); no fixed geometry for electrostatic field  
                        is uniform in all directions
; readily soluble with polar water
[Na+,K+,Ca+2,Mg+2,Cl-]*
DIPOLES*        attractions via asymmetrical, internal distribution of charges in a molecule, 
                       
which has no net charge (opposite poles +/- attract)
DISPERSION* (van der Waal’s) Forces- electrostatic interaction between orbitals of 2 atoms that
                        generates transient dipoles that attract/repel; results is cohesion between non-
                        polar molecules that don't form H-bonds  mcb fig 2.10  important in 3-D shapes
HYDROPHOBIC Interactions* - repulsion of electrostatic dipoles of water by non-polars-
                                              "fatty-hydrocarbon" groups self assembly - "
like dissolves like*"
HYDROPHILIC Interactions* - substances that dissolve readily in water (ions & polar molecules) 
                                                water, as a dipole, surrounds & solubilizes a solute molecule
HYDROGEN bonds*  [fig] - electrostatic attraction between H of one atom & pair of non-bonded
         
e-’s on an acceptor group; linear directionality.  
O-H  &  N-H  with   O-  &  N-   see 2.6a
  Non-covalent Electrostatic Interactions*...    (in the 10-150 cal/mol range)

 

 

 

 

 

 
 
Covalent & Weak Molecular Forces of Life
 ...                

TYPE of BOND ENERGY (Kc/mol) TYPE of INTERACTIONS ENERGY (Kc/mol)
SINGLE COVALENT BONDS NON-COVALENT BONDS
O - H 110 IONIC BONDS 1.0 -  5.0 
H - H 104 HYDROGEN BONDS 1.0 -  2.0
C - H 99 VANDER WAALS 0.1 -  1.0
C - O 84 HYDROPHOBIC 0.1 -  1.0
C - C 83
S - H 81
C - N 70
C - S 62
DOUBLE BONDS
C = O 170
C = N 147
C = C 146

                                            fig 2.6 relative bond energies* 

 

 

 

 

 

 

 
 Biological Design or   How Shape & Weak Molecular Forces may build FORM
  

   Tensegrity- (tensional integrity)  where a structure maintains stability under tension;
        it may be
an architectural principle that helps contributes to biological form & shape.
     

      
   a basic question of the living condition has always been (???) 
               
How do individual groups of molecules assemble themselves within living organisms?
         
Is there a fundamental principle that guides biological organization ?
         
             obviously some common-universal rules of molecular assembly may exist…
            
                   one sees recurring patterns of spirals, triangulated forms, & pentagons in
                               
everything from
crystals to proteins, viruses to plankton
, paramecia to protozoa. 
   

 
      ...Is there some PRINCIPLE of SELF-ASSEMBLY...
         molecules join to form larger & more stable structures, often
with new & non-predicted properties
         or
emergent properties…
   macromolecules -> organelles -> cells -> tissues -> organs
                    
     maybe the answer lies in the principles of  TENSEGRITY... 
                     
    the application of general architectural principles
to biomolecules & living systems 

TENSEGRITY defines the mechanical rules of how structures are stabilized
by balancing forces of internal tension and compression [tensional integrity].

    

   
 

 


 

 

 
 TENSEGRITY
may be a fundamental aspect of SELF-ASSEMBLY
               
                       an architectural system, mechanically stable, yet dynamic, 
                                      where the forces of  tension and compression balance. 
          
"tension & compression are eternally complementary elements in any structure

      Geodesic Domes   (Buckminster Fuller
     
        an entire structure distributes its mechanical stresses... 
  
                               on frames of rigid struts connected into 
                                 triangles,
pentagons, or hexagons…
     
                           each of which bears tension or compression.

  
 Prestress Structures
(Ken Snelson  pic) -
      struts that bear tension are distinct from ones bearing compression.
 Compression members can provide rigidity while remaining separate,
 
     not touching one another, held in stasis only by means of tensed wires.
             click on pic*
 

   
                In both of these structures tension is continuously 
                   transmitted across all structural members.    


 
                    some toy models  -   models*   and   picture   and     straw structures  

 

 

 

 


  
Tensegrity
in Biological Systems
 ???         

   Organismal Level   (a crude example...)  
                  
bones are the compression struts and
                  
muscles, tendons, & ligaments are the tension bearing wires

   Cell (1970’s view) membrane bounded viscous gel (molasses filled balloon)
     
              today's...
cytoskeletal*  microtubules awash in a viscous gel,
                                                          tensed by microfilaments, surrounded by membrane

    

                                                
fluorescent picture of cytoskeleton      cytoskeletal elements
   

              cytoskeletal
elements as the microtubules...   may act as compression "girders";
             
and microfilaments exert tension, pulling all a cell's parts toward nucleus

    
  
      ► the Cytoskeleton then may be a hard-wired molecular system that stabilizes
              cell form & shape, according to the architectural principles of tensegrity?

                                              

    

 

 

 

 

 
 
Biological Tensegrity suggests - 
       that the structure of cell's cytoskeleton can be changed by altering 
       the balance of physical forces transmitted across the cell’s surfaces.  
              for examplecultured cells on glass
[flat]  vs.  a flexible surface [round]
                         
Donald Ingber’s Tensegrity Model of a Cell*    &   'Architecture of Life'   by Don Ingber

 Tensegrity further suggests – 
   
 Since many enzymes and other substances that control protein synthesis, energy
     conversion, & growth in the cell are physically
immobilized upon the cytoskeleton,
    
changing the cytoskeletal geometry & mechanics may affect biochemical reactions  
     & even alter the genes, which may be activated & thus proteins may be made.

                                                                                                                    
mcb fig 6.5
   
Binding a signal molecule (or mechanical stress) to a receptor, which traverses a cell
    membrane into a cell, MAY CAUSE conformational changes at the opposite end of
    the receptor, which may then trigger a cascade of molecular restructuring inside
    a cell, including reorientation of the cytoskeleton.
                 cellular mechanotransduction*   

 

 

 


   
SELF-ASSEMBLY
of molecules into organelles and/or cells into tissue 
             is
not much different from self-assembly of atoms into compounds. 
                                The shape a molecules assumes is characteristic of the way 
                                the structure as a whole will behave in 3-D space, and maybe  
                                cells respond in a similar way according to rules of
Tensegrity

  µ Fully triangulated tensegrity structures, once self assembled, 
       may have been
selected for through evolution,
because of their
     
   structural efficiency, their high mechanical strength, & minimal use of materials.

     Tensegrity may be the most economical and efficient way to build cell structure.


     

 

 

 

 

 

 

 
  
SUMMARY:
      
a few fundamental principles of chemistry are essential for understanding
       cellular processes at the molecular level:

  

            
1.  covalent and non-covalent electrostatic forces control MOLECULAR form and shape...
                          forces of configuration & conformation & result in biologically active molecules
                          figure 2.1a
*
            
2. small molecules are the building blocks of larger molecules...
                         
monomers make polymers, make supramolecular complexes, make organelles...
                          fig 2.1b
*
     
 more of the details of 3 and 4 will be covered under metabolism.
            
3. chemical reactions are reversible depending on rate constants & the [P] & [R]
                          fig 2.1c
            
4. the source of cellular chemical energy is the hydrolysis of ATP, as high energy
                          phospho-anhydride bonds are broken by addition of water (hydrolysis).
                          fig 2.1d
 
                                                         © Charles Mallery -CASUM - last update 16 September, 2008    

 

 

 

 

 

 

 

 

3.  The Design of Metabolism... 
 

            6 major categories of bio-chemical reactivity 
              
Chemical reactivity is bond breaking & reforming  
               these are violent events inside cells, carefully controlled by enzymes

1. functional group transfers glu + ATP <--> G6P + ADP
2. redox reaction (oxidation/reduction) PGAld + NAD+ <-> 1,3di-PGA + NADH
3. rearrangement (isomerizations) glucose-6P <--> fructose-6P
4. C-C breaking or re-formation fruc1-6bP <--> DHAP + 3PGAld
5. Condensations Protein(n) + aa1 <--> Protein(n+1) + H2O
6. Hydrolysis glu-glu(n) + H2O <--> glu-glu(n-1)