Nucleotides

You might have heard of DNA and RNA: these molecules contain genetic information that determine the characteristics of living things (including us humans!). But do you know what DNA and RNA are actually made of?

DNA and RNA are nucleic acids, and nucleic acids are made up of building blocks called nucleotides. Here we will describe what a nucleotide is, elaborate on its components and structure, and discuss how it bonds to form nucleic acids and other biological molecules.

Nucleotide Definition

First, let's look at the definition of a nucleotide.

Nucleotide vs. Nucleic Acid

Before we proceed, let's make things clear: nucleotides are different from nucleic acids. A nucleotide is considered a monomer, while a nucleic acid is a polymer. Monomers are simple molecules that bond with similar molecules to form large molecules called polymers. Nucleotides bond together to form nucleic acids.

Nucleic acids are molecules that contain genetic information and instructions for cellular functions.

There are two main types of nucleic acids: DNA and RNA.

• Deoxyribonucleic acid (DNA): DNA contains genetic information needed for the transmission of heritable traits and instructions for the production of proteins.

• Ribonucleic acid (RNA): RNA plays a vital role in the creation of protein. It also carries genetic information in some viruses.

It is important to distinguish between the two because the components and structure of nucleotides of DNA and RNA are different.

Components and Structure of a Nucleotide

We will first discuss the main components of a nucleotide before elaborating on its structure and how it bonds together to form nucleic acids.

3 parts of a Nucleotide

A nucleotide has three major components: a nitrogenous base, a pentose sugar, and a phosphate group. Let’s look into each of these and see how they interact to form a nucleotide.

Nitrogenous base

Nitrogenous bases are organic molecules containing one or two rings with nitrogen atoms. Nitrogenous bases are basic because they have an amino group that tends to bind extra hydrogen, which leads to a lower hydrogen ion concentration in its surroundings.

Nitrogenous bases are classified either as purines or pyrimidines (Fig. 1):

Figure 1. Adenine (A) and guanine (G) are purines, while thymine (T), uracil (U), and cytosine (C) are pyrimidines.

Purines have a double ring structure wherein a six-membered ring is attached to a five-membered ring. On the other hand, pyrimidines are smaller and have a single six-membered ring structure.

The atoms in nitrogenous bases are numbered 1 through 6 for pyrimidine rings and 1 through 9 for purine rings (Fig. 2). This is done to indicate the position of bonds.

Figure 2. This illustration shows how purine and pyrimidine bases are structured and numbered. Source: StudySmarter Originals.

Both DNA and RNA contain four nucleotides. Adenine, guanine, and cytosine are found in both DNA and RNA. Thymine can be found only in DNA, while uracil can be found only in RNA.

Pentose sugar

A pentose sugar has five carbon atoms, with each carbon numbered 1′ through 5′ (1′ is read as “one prime”).

Two types of pentose are present in nucleotides: ribose and deoxyribose (Fig. 2). In DNA, the pentose sugar is deoxyribose, while in RNA, the pentose sugar is ribose. What distinguishes deoxyribose from ribose is the lack of hydroxyl group (-OH) on its 2’ carbon (which is why it is called “deoxyribose”).

Figure 3. This illustration shows how ribose and deoxyribose are structured and numbered. Source: StudySmarter Originals.

The nitrogenous base of a nucleotide is attached to the 1’ end, while the phosphate is attached to the 5’ end of the pentose sugar.

Phosphate group

The combination of nitrogenous base and pentose sugar (without any phosphate groups) is called a nucleoside. The addition of one to three phosphate groups (PO₄) turns a nucleoside into a nucleotide.

Prior to being integrated as part of nucleic acid, a nucleotide usually exists as a triphosphate (meaning it has three phosphate groups); however, in the process of becoming a nucleic acid, it loses two of the phosphate groups.

The phosphate groups bond to 3’ of ribose rings (in RNA) or 5’ of deoxyribose rings (in DNA).

Nucleoside, nucleotide, and nucleic acid structure

In a polynucleotide, one nucleotide is joined to the adjacent nucleotide by a phosphodiester linkage. Such bonding between the pentose sugar and the phosphate group creates a repetitive, alternating pattern called the sugar-phosphate backbone.

The resulting polynucleotide has two "free ends" that are different from each other:

• The 5’ end has a phosphate group attached.

• The 3’ end has a hydroxyl group attached.

These free ends are used to indicate a directionality across the sugar-phosphate backbone (such direction can be either from 5’ to 3’ or from 3’ to 5’). The nitrogenous bases are attached along the length of the sugar-phosphate backbone.

The sequence of nucleotides along the polynucleotide chain defines the primary structure of both DNA and RNA. The base sequence is unique for each gene, and it contains very specific genetic information. In turn, this sequence specifies the amino acid sequence of a protein during gene expression.

The diagram below sums up the formation of nucleosides, nucleotides, and nucleic acids from the three major components (Fig. 4).

Figure 4. This diagram shows how a pentose sugar, a nitrogenous base, and a phosphate group form nucleosides, nucleotides, and nucleic acids. Source: StudySmarter Originals.

The secondary structure of DNA and RNA differ in several ways:

• DNA consists of two intertwined polynucleotide chains that form a double-helix structure.

  • The two strands form a right-handed helix: when it is viewed along its axis, the helix moves away from the observer in a clockwise screwing motion.

  • The two strands are antiparallel: the two strands are parallel, but they run in opposite directions; specifically, the 5’ end of one strand faces the 3’ end of the other strand.

  • The two strands are complementary: the base sequence of each strand aligns with the bases on the other strand.

• RNA consists of a single polynucleotide chain.

  • When RNA folds, base pairing can take place between complementary regions.

In both DNA and RNA, each nucleotide in the polynucleotide chain pairs with a specific complementary nucleotide via hydrogen bonds. Specifically, a purine base always pairs with a pyrimidine base as follows:

• Guanine (G) pairs with Cytosine (C) via three hydrogen bonds.

• Adenine (A) pairs with Thymine (T) in DNA or Uracil (U) in RNA via two hydrogen bonds.

Nucleoside and nucleotide naming conventions

Nucleosides are named according to the nitrogenous base and pentose sugar attached:

• Nucleosides with purine bases end in -osine.

  • When bonded to ribose: adenosine and guanosine.

  • When bonded to deoxyribose: deoxyadenosine and deoxyguanosine.

• Nucleosides with pyrimidine bases end in -idine.

  • When bonded to ribose: uridine and cytidine.

  • When bonded to deoxyribose: deoxythymidine and deoxycytidine.

Nucleotides are named similarly, but they also indicate if the molecule contains one, two, or three phosphate groups.

Additionally, the name of nucleotides can also indicate the position in the sugar ring where the phosphate is attached.

Nucleotides in other biological molecules

Besides storing genetic information, nucleotides are also involved in other biological processes. For example, adenosine triphosphate (ATP) functions as a molecule that stores and transfers energy. Nucleotides can also function as coenzymes and vitamins. They also play a role in metabolic regulation and cell signaling.