Core Concepts

Nucleotides are the building blocks of DNA and RNA and contain of three parts: phosphate, sugar, and a nitrogenous base. These three simple parts give rise to many emergent properties that allow for life. The structure and properties of nucleotides, and the similarity and difference between nucleotides will be discussed.

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Overall Structure of Nucleotides

Nucleotides are the building blocks of DNA and RNA, which are the molecules of heredity. These highly optimized building blocks are responsible for the structure and reactions of DNA and RNA which are necessary for life. Each nucleotide consists of a sugar with a phosphate on one side and a variable group on another. These phosphate groups connect to the next sugar to form the backbone of DNA and RNA

Nucleic Acid Backbone as a polymer of nucleotides
Backbone structure of a Nucleic Acid: Note the alternating sugar and phosphate.

The variable groups, called nitrogenous bases (or bases of short), encode the information in the genome. But not only do these bases encode our genome, they also interact with other bases in a predictable way so that DNA has its predictable double helix shape and RNA can fold into useful and dynamic shapes. Shapes are very important in biochemistry, and if these shapes were not as they are, life would not be possible.

Pentose Sugar

A pentose sugar is at the core of each nucleotide. These sugars each have 5 atoms that make a closed loop (hence the prefix pent-) with one oxygen atom. DNA and RNA (deoxyribonucleic acid and ribonucleic acid respectively) differ mainly by the sugar used in the backbone. RNA uses ribose (left) and DNA uses deoxyribose (deoxy meaning without oxygen). The picture below shows this fundamental difference between the two sugars:

Ribose and Deoxyribose
Ribose (Right) and Deoxyribose (Left) Differ by only one alcohol group (highlighted in red)

DNA does not use this oxygen atom because it would clash with the backbone, making the critical double helix structure not possible. RNA uses this oxygen atom because it is actually energetically cheaper to keep this oxygen on, and RNA is all about being cheap because it is a temporary molecule. Additionally, these sugar molecules connect to the phosphates in between them at the breaks in the molecules shown above, which are both the same for ribose and deoxyribose. The bottom left corner of the ribose molecule is the 3′ (three prime) carbon and the carbon that juts off from the top left corner is the 5′ carbon. Biochemists use this to describe which direction DNA and RNA are facing.


Phosphate (PO4) is what links the nucleotides together because it has many desirable chemical and physical properties. It is a ubiquitous group in biological molecules, and comes pre-packed. Because of this, it is very easy to reuse phosphate groups making DNA and RNA molecules cheaper. Additionally, Phosphate has alcohol groups, which can react with the 3′ carbon of another sugar in a condensation reaction to link nucleotides together and produce a water molecule.

Condensation between nucleotides
Nucleotide Condensation: Two deoxynucleotides condense to form a dinucleotide and water.

Speaking of water, phosphate, when in the form of DNA, has a negative charge, which attracts the positive hydrogens of water molecules. Water stabilizes the DNA and RNA molecules, and makes sure they don’t tangle or twist.

DNA double helix stabilized by water
Water Molecules Associate with the Phosphate Backbone to Stabilize It (PDB: 5DNB)

Nitrogenous Bases

The third part of each nucleotide is a nitrogenous base. These molecules are full of nitrogen, and have slight Lewis basicity from the many nitrogen lone pairs. Nitrogenous bases are cyclic and connect to the pentose sugar (at carbon one) at a tertiary nitrogen atom. There are 5 primary nitrogenous bases: guanine, adenine, cytoside, thymine and uracil:

Nitrogenous bases structure
Nitrogenous Bases

Notice anything about the shapes? Guanine and adenine are the purine bases, and contain a bicyclic core. All of the others contain one cycle and are the pyrimidine bases. All of the bases in each family are very similar, which means that the cells can use much of the same machinery to build each of these nucleotides. Building nucleotides needs to be an efficient process because the human body has about  1.2 \cdot 10^{23} nucleotides at any given point in time. On the topic of efficiency, uracil has one less methyl group than thymine because uracil is used instead of thymine in the energetically cheap RNA.

Notice how there are a lot of N-H groups and carbonyl groups pointing away from where the sugar connects. This is because these outward facing sides of the nucleotides hydrogen bond with each other, giving DNA and RNA their characteristic structures.

Hydrogen Bonding Between Nucleotides

Different nitrogenous bases hydrogen bond with each other to create the characteristic shapes we associate with DNA. Below, the hydrogen bonding between guanine and cytosine, adenine and thymine, and adenine and uracil is shown:

Base Pairing Combinations Between Nucleotides
Guanine and Cytosine (Top Left), Adenine and Thymine (Top Right), Adenine and Uracil (Bottom)

These bases only pair in the figure shown because pairing two purines together would cause an unstable bulge in the DNA and pairing two pyrimidines would cause an unstable narrow section in the DNA. Furthermore, Guanine only pairs with cytosine because that complex makes three hydrogen bonds rather the two that adenine can make. To add even more redundancy the non-middle hydrogen bonds must be between a carbonyl and an amine. Any other combinations would violate this rule.

Differences in DNA and RNA Nucleotides

DNA forms a very regular double helical structure. Because DNA has two strands, the helix is the most stable, but this gentle twisting means that deoxyribose is much preferred over ribose. Additionally, DNA safe from degradation with the phosphate groups on the outside and the reactive nitrogenous bases on the inside. Because it offers better protection, the helical shape is preferred. Any damages to the DNA molecules could have disastrous consequences like cell death or even cancer.

RNA, on the other hand is a very temporary molecule, and has only a single strand. RNA folds like a protein, so that some bases may pair with others, but many are largely exposed. These folded RNA preform dynamic functions like shuttling amino acids into the ribosomes, assembling proteins in the ribosomes, and regulating gene expression. Because shape determines function, RNA backbones are much more flexible to achieve these conformation, and the cheaper uracil base is used in place of thymine.

It is quite amazing that simple molecules of only three predictable parts are able to carry the information necessary for cells to live, but also functions as primitive cellular machinery.