Nucleotide Structure | A detailed insight and its significance

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Nucleotide Structure | A detailed insight and its significance

Contents

Except in some viruses, DNA is ubiquitously found in the living forms (except RNA viruses) and acts as genetic material in almost every living form. The nucleotide is considered as building blocks for synthesizing nucleic acids (RNA and DNA). Apart from taking part in the synthesis of nucleic acids, nucleotides are also involved in various other cellular functions depending upon their chemical and structural properties.

Key concept and terms

RNA (Ribonucleic acid): it is present in all the cells exhibiting metabolic activities. It is produced from the DNA and gets involved in the protein synthesis upon the directions given by DNA. RNA acts as a mediator between genetic information and its expression. As the order of expression of the genetic information is from DNA –> RNA –> Proteins.

DNA (Deoxyribonucleic acid): the DNA is ubiquitously found in almost all living organisms. The DNA can self-replicate and synthesize its copies. However, this replication process is initiated and completed by a DNA polymerase enzyme. DNA carries genetic information, and it is found in almost every cell of our body (Absent in RBCs). The DNA has a structure like a double helix.

Monomer: A monomer is a unit (monomer; “mono” means one) that bonds to the other similar units to produce a bigger unit (polymer).

Polymer: A polymer is a bigger unit (polymer; “poly” means many) or unit formed as a result of the association of smaller units (monomers).

Purines: A double-ringed nitrogenous base structure is known as purine (Guanine and Adenine)

Pyrimidine: A single ringed nitrogenous base structure is known as pyrimidine (Uracil, Thymine and Cytosine)

The pyrimidines and purines are the constituent nitrogenous bases found in DNA and RNA.

What is a Nucleotide? | What are nucleotides made of?

The nucleotides are the monomeric units that combine to form bigger molecules (polymers) like RNA and DNA. Nucleotides serve as the basic structural and fundamental unit of a polynucleotide strand. The nucleotides are responsible for the synthesis of the genetic material in all life forms on this planet.

Irrespective of the organism and site of occurrence, nucleotide contains three basic chemical components, which are as follows:

  • Phosphate group (at least one)
  • Pentose sugar (five-carbon sugar which may be ribose or deoxyribose)
  • Nitrogenous base (pyrimidine of purine)
nucleotide structure
Figure: Nucleotide structure and basic difference between nucleotide mono, di and triphosphates https://commons.wikimedia.org/wiki/File:Nucleotide_nucleoside_general_vi.svg

The nucleotides bond together to produce nucleic acid or polynucleotide strands, often regarded as the string of DNA.

Nucleotides sometimes act independently (gene expression) or get involved in the other cellular processes (catalysis and signalling).

Nucleotide structure | Nucleotide monomer

To understand the diverse functioning of the nucleotide, we need to focus on the way they are build and how they combine to become nucleic acid. 

Nucleotide bases (nitrogenous bases)

The nucleotides are differentiated and classified based on the presence of different nitrogenous bases. There are generally five types of nitrogenous bases found in the genome of every organism.

  • Uracil
  • Thymine
  • Guanine
  • Cytosine
  • Adenine

The naming of a nucleotide is determined by the nitrogenous base and the number of phosphate groups present in it. Say, for example, if a nucleotide contains Guanine and one phosphate group, then the nucleotide will be named Guanosine monophosphate (GMP). Here, guanosine refers to Guanine, and monophosphate refers to the single phosphate present in the GMP. 

The nitrogenous bases are broadly classified on the basis of number of rings present into two types, namely, Purines and Pyrimidines. Purines include Adenine and Guanine (They are called Adenosine and Guanosine respectively when present in DNA or RNA. Their name generally end with the suffix ”sine”). In contrast, pyrimidines include Thymine, Cytosine and Uracil (They are called Thymidine, Cytidine and Uridine respectively, when present in DNA or RNA. Their name generally ends with the suffix “dine”).

Adenine (A): Adenine is a purine nitrogenous base with a chemical formula C5H5N5. The nucleotide containing Adenine is known as adenosine. The Adenine binds with thymine with the help of two hydrogen bonds. These interactions help in stabilizing the structure of DNA or RNA. Adenine is also present in ATP (Adenosine triphosphate), which is involved in various cellular processes and energy-driven reactions.

Figure: Structure of Adenine, a purine nitrogenous base
https://commons.wikimedia.org/wiki/File:Adenine.svg

Cytosine (C): it is a pyrimidine nitrogenous base with a chemical formula C4H5N3O. The nucleotide containing cytosine base is known as Cytidine. It has an aromatic heterocyclic six-membered ring. The cytosine pairs with Guanine with the help of three hydrogen bonds. These interactions help in stabilizing the structure of DNA or RNA. The free nucleotide form of cytosine is often involved in the catalysis of reactions like the conversion of ADP to ATP.

Figure: Structure of Cytosine, a pyrimidine nitrogenous base
https://commons.wikimedia.org/wiki/File:Cytosine_chemical_structure.svg

Guanine (G): Guanine is a purine nitrogenous base having a chemical formula C5H5N5O. The nucleotide containing Guanine is known as guanosine. Guanine is a double-ringed structure with conjugated single, double bonds, and it forms three hydrogen bonds with cytosine and stabilizes the DNA structure.

Figure: Structure of Guanine, a purine nitrogenous base
https://commons.wikimedia.org/wiki/File:Guanine.svg

Thymine (T): It is a pyrimidine nitrogenous base with a chemical formula C5H6N2O2. The nucleotide containing a thymine base is known as thymidine. It looks like a fused ring and forms two hydrogen bonds with Adenine, which helps stabilize DNA structure. 

Figure: Structure of thymine, a pyrimidine nitrogenous base
https://commons.wikimedia.org/wiki/File:Thymine_(structural_formula).png#/media/File:Thymine_(structural_formula).png

Uracil (U): it is a pyrimidine nitrogenous base exclusively found in DNA. It acts as a weak acid and has a chemical formula C4H4N2O2. The nucleotide containing Uracil is known as Uridine. The Uracil differs from thymine just by the absence of a methyl group; hence, its structure is similar to that of thymine.

Figure: Structure of Uracil, a pyrimidine nitrogenous base exclusively found in RNA
https://www.flickr.com/photos/71728339@N03/6480986657

Pentose sugar (monosaccharides)

Pentose sugar is an essential element in forming a nucleotide, while it also provides a backbone for the structure of nucleic acids. The pentose sugar contains five carbon atoms. Nucleotides have two types of pentose sugars:

  • Deoxyribose (found in DNA)
  • Ribose (found in RNA)
Figure: Structure of Ribose (left) and deoxyribose (right). In the structure of deoxyribose, one oxygen atom is missing https://commons.wikimedia.org/wiki/File:The_difference_between_ribose_and_deoxyribose.png

Phosphate group 

The phosphate groups present in the nucleotides are derived from phosphoric acid. It has a general formula of (PO4)3- and it is found in the nucleotides as mono, di or tri-phosphates. The nucleotide containing one, two, and three phosphates is monophosphate, diphosphate, and triphosphate.

The exact naming of nucleotides is done by considering the sugar, nitrogenous base and number of phosphate groups present. For example, ATP is Adenosine triphosphate while dGDP is deoxyguanosine diphosphate. The letter “d” in the nucleotide name indicates the presence of deoxyribose sugar in the nucleotide.

Figure: Structure of phosphate group. The presence of phosphate group is the criteria for differentiating between nucleoside and a nucleotide https://commons.wikimedia.org/wiki/File:Phosphat-Ion.svg

What nucleotides do?

The DNA and RNA of an individual are generally made up of strings of nucleic acids (polynucleotides). The gene expression inside cells of organisms are constantly changing every time, and the cells of the organism are simultaneously growing and dying.

Nucleotides play a key role during this entire process.

  • The nucleotides regulate the process in combinations like in nucleic acids
  • The nucleotides also regulates the metabolic process while present in the free form (not associated with the nucleic acid)

When nucleotides form DNA double-helical structure, they form complementary base pairing among the nucleotides present on opposite polynucleotide strands. 

The thumb rule of complementarity is that the purine present on one strand base pairs with the complementary pyrimidine present on the other strand (Guanine pairs with Cytosine and Adenine pairs with Thymine). 

  • Purines include Guanine and Adenine
  • Pyrimidines include Uracil, Thymine and Cytosine

DNA nucleotides

Following are the nucleotides that make DNA:

Deoxyguanosine triphosphate (dGTP): It’s a purine nucleotide made up of three phosphate groups, deoxyribose sugar and a guanine base.

Deoxythymidine triphosphate (dTTP): It’s a pyrimidine nucleotide made up of three phosphate groups, deoxyribose sugar and a thymine base.

Deoxycytidine triphosphate (dCTP): It’s a pyrimidine nucleotide made up of three phosphate groups, deoxyribose sugar and a cytosine base.

Deoxyadenosine triphosphate (dATP): It’s a purine nucleotide made up of three phosphate groups, deoxyribose sugar and an adenine base.

RNA nucleotides

Following are the nucleotides that make RNA:

Guanosine triphosphate (GTP): It’s a purine nucleotide made up of three phosphate groups, a ribose sugar and a guanine base.

Uridine triphosphate (UTP): It’s a pyrimidine nucleotide made up of three phosphate groups, a ribose sugar and a uracil base.

Cytidine triphosphate (CTP): It’s a pyrimidine nucleotide made up of three phosphate groups, a ribose sugar and a cytosine base.

Adenosine triphosphate (ATP): It’s a purine nucleotide made up of three phosphate groups, a ribose sugar and an adenine base.

Free Nucleotides

Only nucleotide triphosphates interlink to form nucleic acids, nucleotide monophosphates and nucleotide diphosphates do not incorporates into polynucleotide strands and are present in the cell as free nucleotides. However, mono and diphosphate nucleotides are involved in other essential cellular processes and metabolism. The free nucleotides also act as co-enzymes for various enzymes for the catalysis of biochemical reactions. 

Say, for example, ATP acts as an energy-rich molecule and co-enzyme for many biochemical reactions. ATP is often needed to initiate a variety of biochemical reactions inside our body. 

Free nucleotides also have a role in cellular apoptosis. Changes in the nucleotides activate the proteasomal machinery of the cell, which leads the cell towards programmed cell death, also known as apoptosis. Apoptosis is an important phenomenon taking place inside our body. It provides our body with a proper shape as well as prevents our body from various genetic diseases.

Conclusion

In this article we have discussed about the structure of nucleotides in detail. They have a crucial role in forming the genetic material (DNA and RNA). However they also play roles in the breakdown and degradation of damaged cellular components which will be discussed in our upcoming posts. 

Interview Q & A related to this topic

Q1 Name the four types of nucleotides?

Answer: There are five types of nucleotides collectively present in the DNA and RNA. Namely: Adenine, Guanine, Thymine, Cytosine and Uracil. Out of which Adenine, Guanine and Cytosine are common among DNA and RNA. While the DNA contains thymine, and RNA contains Uracil in place of thymine.

Q2 Name the three components of a nucleotide?

Answer: A nucleotide contains three structural components (building blocks), which are as follows:

  • a nitrogenous base [Purine (Adenine and Guanine) or Pyrimidine (Thymine and Cytosine)], 
  • a five-carbon sugar (Ribose sugar in case of RNA and Deoxyribose sugar in case of DNA) 
  • and a phosphate group.

Q3 What is the function of nucleotides?

Answer: The primary function of a nucleotide is to build DNA and RNA, which stores the genetic information of an organism. Nucleotides are also involved in cellular signalling pathways (cAMP acts as a secondary messenger). Nucleotides such as ATP and GTP are often engaged in the energy-driven mechanisms of the body. Some of the nucleotides like NAD, NADH, NADP, NADPH etc., often acts as cofactor for the enzymes carrying out various metabolic processes.

Q4 Where are nucleotides found?

Answer: The nucleotides are abundantly present in the cell’s nucleus as they are the building blocks of DNA or RNA. Some nucleotides are present in the cytoplasm as they are also involved in the biochemical pathways. Lastly, nucleotides involved in the cell signalling pathways are also present in extracellular environments.

Q5 Is DNA a nucleotide?

Answer: DNA comprises a large number of nucleotides. Thus, it is known as a polynucleotide. 

Q6 What is a nucleotide diagram?

Answer: For details about nucleotide structure Click here

Q7 How nucleotide is formed?

Answer: Nucleoside formation is the primary step in the formation of nucleotide. A nucleoside is synthesized after a pentose sugar links with a nitrogenous base through N-glycosidic bond. The formed nucleoside reacts with a phosphate group and undergoes an esterification reaction to produce nucleotide. Chemically, a nucleotide is a phosphate ester of the nucleoside.

Q8 Nucleotide vs nucleoside

Answer: The basic difference between a nucleotide and a nucleoside is the presence of phosphate group. The nucleoside contain nitrogenous base and a ribose sugar while nitrogenous base contains nitrogenous base, ribose sugar and a phosphate group.

Q9 What nucleotide pairs with cytosine?

Answer: Guanine forms complementary base pair with cytosine. Guanine forms three hydrogen bonds with cytosine. This guanine and cytosine base pairing is a major stabilizing force in the DNA.

Q10 Name the nucleotide is not found in RNA?

Answer: Thymine is not found in the RNA. Uracil is only found in RNA as a replacement for thymine. Thymine is involved in the repair mechanisms, but no such repair mechanism is required in the RNA. Hence RNA contains Uracil in place of thymine.

Q11 what nucleotide is always paired with thymine?

Answer: Adenine always pairs with thymine. The complementary base pair for thymine is adenine in the biological system. Adenine of one DNA strand forms two hydrogen bonds with thymine of other DNA strand which contributes towards stabilizing the DNA.

Q12 Where is the nucleotide located in the cell?

Answer: nucleotides are located in the entire protoplasm of the cell. But abundantly found in the nucleus. Nucleotides are also found in the cytoplasm and extracellular environments.

Q13 where is the nucleotide on a DNA strand?

Answer: The DNA strand is known as the polynucleotide strand; hence it is made up of multiple units of Nucleotides. Nucleotides are found in the entire length of DNA.

Q14 What nucleotide will pair up with Guanine?

Answer: Cytosine present on the other DNA strand forms complementary base pair with Guanine. Three hydrogen bonds are formed between cytosine of one DNA strand and Guanine of other DNA strand.

Q16. Name the three components of a single nucleotide?

Answer: The three basic components of a single nucleotide includes: a nitrogenous base (purine or pyrimidine), a ribose sugar (ribose or deoxyribose) and a phosphate group.

Q18. How can you compare and contrast nucleotide and nitrogenous bases?

Answer: Nucleotide is the fundamental unit of the nucleic acids (DNA/RNA) which includes nitrogenous base, ribose sugar and phosphate group. Whereas nitrogenous itself is one of the components of nucleotide.

Q19. What does nucleotide analogue mean?

Answer: Nucleotide analogue is the derivatives of standard nucleotides or structurally similar molecules that look like nucleotides, but they do not perform the function usually carried out by nucleotides.

Q20. What parts of DNA nucleotide are most important?

Answer: Nucleotides are characterized based on the presence of a type of nitrogenous base. Hence, the nitrogenous base is the most important part of a nucleotide. DNA stores genetic information in the form of nucleotide sequence. The presence of different nitrogenous base is responsible for making combinations and sequences in the DNA.

About Dr. Abdullah Arsalan

I am Abdullah Arsalan , Completed my PhD in Biotechnology. I have 7 years of research experience. I have published 6 papers so far in the journals of international repute with an average impact factor of 4.5 and few more are in consideration. I have presented research papers in various national and international conferences. My subject area of interest is biotechnology and biochemistry with special emphasis on Protein chemistry, enzymology, immunology, biophysical techniques and molecular biology.

Let's connect through LinkedIn(https://www.linkedin.com/in/abdullah-arsalan-a97a0a88/) or Google scholar(https://scholar.google.co.in/citations?user=AeZVWO4AAAAJ&hl=en).

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