Shape and Form in Molecules, Biological Activity and the Chemical Reactions Characteristic of Cells.  

Key Points
    1.   
How does a molecule's spatial pattern influence its reactivity.
   
2.   Can a change in the contour of a molecule alter its ability to function properly
   
3.   Are all cellular reactions alike?

            Small biomolecules make big molecules, macromolecules.  Macromolecules have molecular weights between 10,000 and several million Daltons.  These immense organic molecules make up the structure and function of life.  What keeps a molecule, such as the multi-subunit enzyme pyruvate dehydrogenase, which is made 24 individual proteins and 5 different organic coenzymes, in its proper 3-D shape to perform its chemical reactivity. The ribosome, which is the cell organelle universally responsible for protein synthesis, is made of a complex of 30 to 40 proteins and 4 to 5 different RNA molecules.  What holds all these molecules in the proper contour and allows them to perform biological work?

            Let's look at two unique properties about biomolecules, which gives them their unique fitness for the living condition. Configuration is the spatial arrangement of atoms in a molecule that comes about due to chemical bonds. A molecule's configuration can not be interconverted without breaking chemical bonds.  Configuration provides a molecules specific orientation in space and the isomers of the hexose sugars noted above are good examples.

Carbon=carbon double bonds, when formed, prohibit the previously free rotation of atoms attached to the C-C (single) bonds. A double bond fixes the atoms either above or below the plane of the double bond and thus results in a specific configuration, which can be recognized by other molecules, such as enzymes, and used to do biological work.  11-cis-retinal is the molecular configuration of the visual chromophore of the human eye pigment, rhodopsin. The cis-isomer has atoms on the same side of a C=C.  Absorption of light changes the 11-cis-retinal to 11-trans-retinal, a straighter shaped molecule with its atoms on the different sides of the C=C.   This part of the human visual cycle, called photo-isomerization, results in the absorption of light energy causing the molecule to twist into a new shape.  This change in shape causes the visual pigment rhodopsin to also change its shape. These changes in shape induce further alterations in the light-absorbing character of the pigment. Eventually an actual shift of the retinal part of the pigment molecule from a lipid linkage to a protein linkage occurs.  It may be that this particular shift is sufficient to lead ultimately to electrical discharges in the optic nerve, which is then perceived as vision.

            The second property is one of conformation, the 3-D shape of a thing.  Conformation is the 3-dimensional outline, contour, or surface structure of a molecule as determined by the arrangement of its interacting parts.  Conformation refers to the spatial orientation of atoms and functional groups, which are free to assume different positions in space without breaking any chemical bonds.  Macromolecules can assume many different conformational shapes via the interaction of their atoms or functional groups with the local environment.  Changes in temperature, pH, ionic strength, etc, all permit the alternating of a molecules conformation between a variety molecular shapes.  Generally, only one specific shape or form of a molecule is the one that is most biologically active.  Enzymes, because of their own variety of conformational shapes, can easily distinguish between the biologically active forms of other molecules.

            A biomolecule, which has chemical reactivity within a living cellular systems, is said to be biologically active. Chemical reactivity in cells is best defined as bond breaking and reforming. These are often violent events inside of cells and are therefore carefully controlled by enzymes. It is this chemical reactivity of the biomolecules, found in all cells, that imparts the properties of life to the cells.

        Millions of combination of atoms form molecules which are chemically reactive, yet as we have seen chemical reactivity in biomolecules may be governed by the concept of functional groups, which exhibit only few reaction types. Of the thousands of theoretically possible chemical reactions that could occur in living systems, very few actually do.  Table 1 presents some of the more important types of chemical reactions, which do occur in cells and therefore help define biological activity and life.




 Table 1. Some Important Chemical reactions of Cells

1. functional
    group transfers

relocation of a functional group from one molecule to another;
           example:
transfers a PO4from ATP to glucose
         
          glucose + ATP  <-->  glucose-6-phosphate +  ADP

2.   redox reactions            (oxidation/reduction)

Oxidation is the removal of an electron from a donor (more electropositive molecule), while reduction is the gaining of an electron by an acceptor (more electronegative) molecule; 
            example: a hydride ion from the aldehyde is donated to the oxidized
                         form of the coenzyme NAD+ reducing it to NADH
        Phosphoglyceraldehyde + NAD + <--> 1,3di-phosphoglycerate + NADH

3.     rearrangement
        reactions

   (isomerizations)

a compound is transformed into any of its isomeric forms, generally with different physical and chemical properties;
         example glucose-phosphate is converted to fructose phosphate

                glucose-6-phosphate  <-->  fructose-6-phosphate

4.  C-C breaking or
       re-formation

The breaking of a carbon-carbon single bond with it reformation;
example: fructose-1-6-biphosphate is split forming dihydroxy-acetone
                  phosphate and 3 phosphoglyceraldehyde
fructose-1-6biphosphate  <-->  DHAP  + 3-phospho-glyceraldehyde

5.   Condensation
      reactions

the class of biosynthetic cellular reaction where two molecules combine with elimination of water or some other simple molecule; the cellular macromolecules, polysaccharides, proteins, lipids, and nucleic acids are made by condensation reactions; example protein biosynthesis
       protein(n units) + aa1  <--->  protein(n+1 units) + H2O

6.  Hydrolysis reactions

cleavage of a molecule, often a polymer, by reaction with water, with insertion of the elements of water ( H and OH) into the final products
         example: hydrolysis of polysaccharide glycogen
           glucose-glucose(n units) + H2O  <-->   glucose-glucose(n-1 units)

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