Small Biomolecules - Amino Acids and Nucleotides - Structural Dimorphism and Reactivity

Key Points

    1.  Can a molecule be both positively charged and negatively charged at the same time?
2.  What are the characteristics of an informational molecule?

            We will look at the amino acids to build upon this idea of chemical dimorphism providing molecules with multiple reactivity, thus allowing them to create a greater complexity of form and function with other cellular molecules. Amino acids are molecules consisting of a basic amino group (-NH 2), an acidic (carboxyl) group (-COOH), and a variable organic R group (or side chain) that is unique to each amino acid. Two amino acids, proline and hydroxyproline, have a secondary amino in their R group that is present in a cyclic structure. More than 150 amino acids occur naturally, but only 20 are commonly used by cells in protein synthesis.  These 20 amino acids are the same in all living organisms, from protozoa to plants and animals. The universality of these biomolecules suggests that once such a molecule was established in a primordial cell it was favored energetically and preserved throughout evolution (more evidence in support of a single progenitor cell establishing living systems).  Humans can not synthesize approximately 10 of the (essential) amino acids, which makes them a dietary necessity. The remaining amino acids (nonessential) are synthesized by cells in an oxidation-reduction reaction called transamination, where an amino group is added to a carbon skeleton, itself a by product of cell metabolism.  Amino acids can be linked together through a covalent bond (peptide bond) between the amino group of one amino acid and the carboxyl of another, in a condensation reaction, which eliminates water. The proteins that result are a linear sequences of amino acids in a specific sequential  order. Many common proteins contain around 100 amino acids. A protein of 100 amino acids made from 20 different types of amino acids can have 20 10 different linear arrangements.  This enormous diversity of possible protein structure is another chemical property, which has made the biomolecules, such as the amino acids, highly preferential in living systems. The chemical property common to all amino acids , that has made these biomolecules highly preferred in living systems, is the special dimorphic arrangement of their carboxyl and amino groups. 

        The structural and chemical properties of the amino acid R groups results in the amino acids being grouped according to the polarity (their tendency to interact with water at a neutral pH) and the charge of the R group.  In a cytosolic solution amino acids can act as both weak acids and weak bases.  Depending upon pH the carboxyl group may lose a hydrogen ion and become negatively charged, and the amino group can pick up a hydrogen ion and becomes positively charged. The individual carboxyl and amino groups of amino acids, when linked through peptide bonds into proteins, no longer are able to act as acids or bases. Proteins still contain acid-base properties, but it is dependent upon the ionization properties of the R groups of the individual amino acids. 

            The last of the small biomolecules are the nucleotides.  A nucleotide is composed of three parts: a) a phosphate, b) a pentose sugar (ribose or deoxyribose) and one of two types of nitrogenous bases (purine or pyrimidine). The five common nucleotides are symbolized by the letters A (adenine), U (uridine), C (cytosine) , G (guanosine), and T (thymidine), which represents the nitrogenous bases found in their respective nucleotides. Nucleotides form the energy rich compounds of cells (ATP and GTP).  They also can be linked into polymeric (polynucleotide) chains by forming a covalent ester-type (phosphodiester) bond between the phosphate of one nucleotide and the sugar of another nucleotide. Thus nucleotides are the precursors of the nucleic acids (DNA and RNA). This unique ability of nucleotides to polymerize into linear informational chains producing a self-replicating, mutable molecular system of polynucleotides, capable of interacting with the environment, may be all that would have been necessary for the origin of life. 

            DNA is the repository of hereditary (evolutionary and developmental) information and is thus called an informational biomolecule. Proteins are so closely related to the information contained in the DNA that they also are often referred to as informational macromolecules. The nucleic acids and proteins are linear polymeric molecules made up of sequences of individual units, nucleotides in the case of nucleic acids, and amino acids in the case of proteins.

            What makes polymeric proteins and nucleic acids informational, while polymers as amylose and cellulose do not seem to contain information. Polysaccharides often contain only one specific type of monomer building block, and fats, while they can be are made of different fatty acids, are not repeat polymers. Nucleic acids contain five different unitary building blocks and proteins are made up of 20 different amino acids. Particular sequence of three nucleotides in DNA act as a pattern, or a code, for the production of precisely the same amino acid in all organisms. This is similar to a language using a particular combination of letters to represent a word and its meaning. 

        Nucleic acid and protein polymers can string together patterns of monomers into "words" or unique sequences that specify another molecule and therefore are informational.  Three nucleotides make a codon, which specifies an amino acid, and amino acids in unique sequences can create local regions of chemical reactivity within a protein, say an active site with the affinity for a hydrophobic substrate. Since they are repeats of only the same monomer, polysaccharides lack the ability to string together sequences of monomers with informational content.  

        Sequencing of these informational words in the nucleic acids can be used to compare organisms phylogenetically. Comparing the amino-acid sequence of human and rhesus monkey cytochrome-C, a protein involved in cell respiration, reveals differences at position 66 (isoleucine in humans, threonine in rhesus monkeys), but identical amino acids at all the other 103 positions. When horses are compared with rhesus monkeys there are only 11 amino-acid differences. When humans are compared with horses, 12 amino-acid differences are found. The degree of sequence similarity suggests a recency of common ancestry. Thus, without knowing much about the evolutionary history of mammals, one could still conclude that the lineage's of humans and rhesus monkeys diverged from each other much more recently than they diverged from the horse lineage. Moreover, it might be concluded that the amino-acid difference between humans and rhesus monkeys must have occurred in the human lineage after its separation from the rhesus monkey lineage. Comparing the fats and polysaccharides of humans, horses, and rhesus monkeys shows no structural differences in these molecules.