Nucleotides: Building Blocks of Nucleic Acids

• Series of these covalent linkages among nucleotide units form the polymer nucleic acids.
• DNA molecules^[2] are composed of two strands of these polymers and are coiled in a so-called “double helix“^[2]. RNA molecules on the other hand are single stranded and just have some regions where the strand twists.
• American biochemist, Phoebus Levene^[3] first coined the term “nucleotide” in the 1900s, long before James Watson and Francis Crick discovered the structure of the DNA.

The structure of the nucleotide^[4] maximizes bonding potential as it allows same building blocks to be connected to one another through the formation of hydrogen bond between each nucleotide’s nitrogenous base.

Such structure is also efficient in allowing the creation of phosphodiester bonds between the pentose sugar of one nucleotide to the phosphate group of another. These connections, therefore, contribute to giving the DNA’s “double-stranded” ladder-like figure.

• While they seem to be almost indistinguishable, nucleotides and nucleosides can be differentiated through their presence of phosphate groups in their structure; Nucleosides can be phosphorylated to produce nucleotides.

A pentose sugar is a five-carbon sugar that serves as the polymer backbone of DNA and RNA. RNA has the ribose sugar while DNA has the deoxyribose. The two differ regarding the functional group attached to the second carbon position. An -OH group can be found in ribose while deoxyribose has hydrogen instead.

• The difference in the number of oxygen atoms^[5] in their structures serves as markers for enzymes to easily distinguish them from each other.
• Also, this functional group difference makes the RNA relatively less stable than DNA. Because of the -OH group, RNA is readily hydrolyzed at basic pH.

Along with the pentose sugar, the phosphate group makes up the polymer backbone of DNA and RNA. The group is attached to the fifth carbon in place of the hydroxyl group.

• The phosphate group^[6] determines the direction of the nucleic acids. The double-stranded nature of the DNA can be attributed to the twisting of the polymer backbone. It is also negatively charged and can easily bond with water molecules.

Through his observations, Phoebus Levene discovered that the genetic material is made up of four smaller sub-units distributed in equal quantities.

• These were later found to be the nitrogenous bases adenine, guanine, cytosine, thymine, and uracil. These five bases are further classified into two groups namely: pyrimidines and purines. Cytosine, thymine, and uracil are the pyrimidines while adenine and guanine are the purines.
• As its name suggest, A nitrogenous base is a molecular structure that contains nitrogen and acts as a base during a reaction.

As alluded to earlier, adenine^[7] belongs to the purines which are composed of a nitrogen group with six members of nitrogen ring attached to a ring with five nitrogen units. In DNA, adenine pairs with thymine whereas in RNA, it pairs with uracil.

Chemical formula for Adenine: C₅H₅N₅.

• When fused with ribose, adenine forms the nucleoside adenosine. On the other hand, when fused with deoxyribose, it forms deoxyadenosine.
• This adenosine is an essential component of adenosine triphosphate (ATP) which is a unit of energy and is utilized during metabolism.

Also a purine molecule, guanine^[8] is composed of a fused system of pyrimidine and imidazole ring with double bond conjugates. This bicyclic molecule is planar due to being unsaturated.

Chemical formula for Guanine: C₅H₅N₅O.

• As a nucleoside, guanine is called as guanosine.
• Guanine pairs with cytosine.

The next base is the cytosine^[9] , a pyrimidine base that pairs with guanine. When combined with ribose, cytosine forms the nucleoside cytidine. This molecule can then be further phosphorylated to form phosphoric groups.

Chemical formula for Cytosine: C₄H₅N₃O.

• Cytosine is very essential in cancer biology since its deamination alone is the main cause in the formation of cancer like leukemia.

Derived from the hydrolysis of deoxyribonucleic acid via catalytic reduction,thymine^[10] is a pyrimidine base that pairs with adenine in DNA. The bond is secured with a hydrogen bond that stabilizes the structure of the nucleic acid.

Chemical formula for Cytosine: C₅H₆N₂O₂.

• In RNA, uracil replaces thymine at carbon five positions.

Uracil^[11] is a pyrimidine that replaces thymine in RNA and therefore is the one that pairs with adenine. Through methylation, uracil can be converted into thymine.

Chemical formula for Cytosine: C₄H₄N₂O₂.

• In the body, uracil is used to synthesize various enzymes which are necessary for the correct functioning of cells.

As building blocks of nucleic acids, nucleotides primarily aid in storing genetic information that will be later the basis for the manifestation of physical traits. Moreover, they also play roles in various biological and physiological processes. As molecules, they help in the transport of ATP and serve as biological catalysts in most reactions involving biomolecules.