Nucleotide

Define Nucleotide: 

Nucleotides are biological compounds made up of nucleoside and phosphate. They act as monomeric units of nucleic acid polymers, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), all of which are important biomolecules of all life forms on Earth. 

Nucleotides are produced in the diet and are also synthesised by the liver from common nutrients. Nucleotides comprises 3 subunit molecules: nucleobase, five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. The four nucleobases in DNA are guanine, adenine, cytosine and thymine; in RNA, uracil is used instead of thymine.

Nucleotide Examples:

• deoxyadenosine triphosphate (dATP)

• deoxyguanosine triphosphate (dGTP)

• deoxycytidine triphosphate (dCTP)

• (deoxy)thymidine triphosphate (dTTP)

• cyclic cytidine monophosphate (cCMP)

• cyclic uridine monophosphate (cUMP)

• deoxyadenosine monophosphate (dAMP)

• deoxy guanosine monophosphate (dGMP)

• deoxycytidine monophosphate (dCMP)

• (deoxy)thymidine monophosphate (dTMP)

• adenosine diphosphate (ADP)

• guanosine diphosphate (GDP)

• cytidine diphosphate (CDP)

• uridine diphosphate (UDP)

Nucleotide Formation

Nucleotides are the nucleoside phosphate esters. Normally, phosphate is mixed with five′ sugar carbon to form nucleotide or nucleoside monophosphate. Nucleotides are adenylate (AMR or adenosine monophosphate), deoxyadenylate (dAMP), cytidylate (CMP of cytidine monophosphate), deoxycytidylate (dCMP),guanylate (GMP or guanosine monophosphate), deoxyguanylate (dGMP), uridylate (UMP or uridine monophosphate) and deoxythymidylate (dTMP). Here, prefixed' is deoxyribose sugar in the nucleotide structure.

In vitro and in vivo, nucleotides could be synthesised in a number of ways.

Protective groups could be used in the laboratory to make nucleotides in vitro. A purified nucleoside is covered to form a phosphoramidite, which could be used to synthesise an oligonucleotide or acquire analogues not present in nature.

In Vivo, Nucleotides can be de novo synthesis or recycled by salvage pathways. The materials used in de novo nucleotide synthesis are derived from biosynthetic precursors of carbohydrate and amino acid metabolism, as well as ammonia and carbon dioxide. The liver is the primary organ in de novo synthesis of all four nucleotides. De novo synthesis of pyrimidines and purines follows two separate pathways. Pyrimidines are first synthesised from aspartate and carbamoyl phosphate in the cytoplasm to the typical precursor ring structure of orotic acid to which the phosphorylated ribosyl unit is covalently bound. Purines, however, are first synthesised from the sugar template on which the ring synthesis is based.

Nucleotide Chemical Structure

A nucleotide is made up of three various chemical subunits, namely a nucleobase (which when paired with one phosphate group is termed as nucleoside), a five-carbon sugar molecule, and single phosphate group. Nucleotides in nucleic acids include either a purine or pyrimidine base—the nucleobase molecule, also termed as a nitrogenous base—and are referred to as ribonucleotides when the sugar is ribose and deoxyribonucleotides when the sugar is deoxyribose.

Individual phosphate molecules link the sugar-ring molecules through two neighbouring nucleotide monomers repeatedly, forming a long chain that connects the nucleotide monomers of such a nucleic acid end-to-end. A single or double helix's 'backbone' strand is made up of chain-joints of sugar and phosphate molecules. 

The chemical alignment (directionality) of chain-joins extends from the 5'-end to the 3'-end (read: 5 prime-end to 3 prime-end) in any given strand, corresponding to the five carbon positions on simple sugars in neighbouring nucleotides.

The two strands of a double helix are aligned in separate directions, allowing base pairing and complementarity amongst base pairs, both of which are required for replicating or transcribing DNA's stored messages/encoded information.

Nucleotide Diagram

Below given picture is the Nucleotide diagram and it represents the nucleotide chemical structure:-

[Image will be uploaded soon]

Types of Nucleotides:

• Adenine Base-The bases have one of two types. Purines consist of a double ring in which the 5-atom ring is attached to the 6-atom ring. Pyrimidines are single rings of 6 atoms.The purines are adenine and guanine. Pyrimidines are cytosine, thyme, and uracil.The molecular formula for adenine is C5H5N5. Adenine (A) is bound to thymine (T) or uracil (U). It is an essential base since it is used not only for DNA and RNA, but also for the energy carrier molecule ATP, the cofactor flavin adenine dinucleotide, and the cofactor nicotinamide adenine dinucleotide (NAD).

• Thymine Base- The chemical equation for pyrimidine thymine is C5H6N2O2. Its sign is T, and it is present in DNA, but not in RNA.

• Guanine Base- The chemical formula for purine guanine is C5H5N5O. Guanine (G) only binds to cytosine (C) in both DNA and RNA.

• Cytosine Base- The chemical formula for pyrimidine cytosine is C4H5N3O. It's a sign of C. The basis is present in both DNA and RNA. Cytidine triphosphate (CTP) is an enzyme cofactor capable of converting ADP to ATP. Cytosine will spontaneously transform into uracil. If the mutation is not reversed, the uracil residue will be left in the DNA.

• Uracil Base- Uracil is a weak acid with the molecular formula C4H4N2O2. Uracil (U) is present in the RNA where it binds to adenine (A). Uracil is the demethylated version of the base of thymine. The molecule is recycled by a series of phosphoribosyltransferase reactions.One curious finding about uracil is that the Cassini mission to Saturn discovered that the moon, Titan, seems to have uracil on its surface.

Nucleotide Function:

• Nucleotides are the base units of nucleic acid (DNA and RNA). While nucleoside monophosphates contained in nucleic acids, nucleoside triphosphates are the raw materials for their synthesis.

• The Cyclic Nucleotides Act as a controlling chemical. Cyclic AMP (cAMP) acts as the second messenger in certain hormone actions, while Cyclic GMP (cGMP) functions in Ca++ or calmodulin mediated reactions.

•  The nucleotides in B-Complex Vitamins function as coenzymes. For eg, NAD+, NADP+, FMN, FAD are useful coenzymes for oxidation-reduction reactions.

• Greater nucleotides are used as energy carriers, e.g. ATP, GTP, UTP and TTP. From these ATPs is the cell's universal energy carrier.

• Higher nucleotides used in polysaccharide synthesis (e.g. UDP-glucose, ADP-glucose) and phospholipids (e.g. CDP and CTP).