Nucleotides: Formation, Higher Nucleotides and Functions (With Diagram)

Let us make an in-depth study of the formation and functions of nucleotides and also about higher nucleotides.

Nucleotides are the building block (monomer) units of the nucleic acids. They constitute about 2% of the protoplasm. A nucleotide is a condensation product of three chemicals – a pentose sugar, a nitrogenous base and one or more phosphate groups.

(a) Pentose Sugars:

Two types of pentose sugars occur in nucleotides – ribose (C₅H₁₀O₅) and deoxyribose (C₅H₁₀O₄). Both the sugars occur in furanose state with one oxygen and four carbon atoms designated as 1’, 2’, 3’, 4’ and 5′. The ribose differs from deoxyribose in having a -OH group instead of- H at C-2 position. Ribose containing nucleotides are called ribonucleotides or ribotides which found only in RNA, while deoxyribose containing nucleotides are called deoxyribonucleotides or deoxyribotides.

(b) Nitrogenous bases:

These are heterocyclic compounds in which the rings contain both nitrogen and carbon atoms. They are of two types, purines (double rings) and pyrimidine’s (single rings). There are two types of purines: adenine (A) and guanine (G) and three types of pyrimidine’s: thymine (T), cytosine (C) and uracil (U). The DNA contains all of the nitrogenous bases except uracil, and RNA contains all of the nitrogenous bases except thymine.

(c) Phosphoric acid (H₃ PO₄):

The phosphoric acid gives the acid nature to the nucleotides and nucleic acids. In a cell, the phosphoric acid found in the form of phosphate group (PO₄^-3) due to dissociation of three H⁺ ions.

Formation of Nucleosides:

A nucleoside is a combination of pentose sugar with a nitrogenous base by N-glycosidic bond. The C-1 carbon atom of pentose is attached to N-1 of a pyrimidine or N-9 of a purine. A nucleoside with ribose sugar is called ribonucleosides or ribosides and a nucleoside with deoxyribose is called deoxyribonucleosides or deoxyribosides.

The different ribosides are adenosine (adenine + ribose), guanosine (guanine + ribose), uridine (uracil + ribose), cytidine (cytosine + ribose) and thymidine (thymine + ribose). Similarly the corresponding deoxyribosides are – deoxyadenosine, deoxyguanosine, deoxycitidine and deoxythymidine.

Formation of Nucleotides:

Nucleotides are the phosphate esters of nucleosides. Normally a phosphate combines with 5′ carbon of sugar to form a nucleotide or nucleoside monophosphate. The various nucleotides are adenylate (AMP or adenosine monophosphate), deoxyadenylate (dAMP), guanylate (GMP or guanosine monophosphate), deoxyguanylate (dGMP), cytidylate (CMP of cytidine monophosphate), deoxycytidylate (dCMP), uridylate (UMP or uridine monophosphate) and deoxythymidylate (dTMP). Here, prefix ‘d’ represents deoxyribose sugar.

Higher Nucleotides:

Nucleotides having more than one phosphate group are called higher nucleotides, e.g. ATR ADP, GTP, GDP etc. Thus, higher nucleotides are nucleoside diphosphates and nucleoside triphosphates. They occur in the free state. The higher nucleotides carry high energy bonds or phosphoanhydride bonds between phosphates and are usually represented by -P (read squiggle phosphate).

ATP or Adenosine triphosphate is the most common energy currency or energy molecule of the cell Karl Lohmann (1929) first discovered ATP in muscle cells, while its role in metabolism first found out in 1941 by Fritz Lipmann and Herman Kalckar. ATP consists of adenosine linked with three phosphoryl groups (-PO₃^2-) commonly referred as and α, β and y-phosphates.

The hydrolysis of ATP release large amount of free energy that drive cellular chemical reactions. In eukaryotic cells, ATP is synthesized from ADP and Pi by oxidative phosphorylation (in mitochondria) and photophosphorylation (in chloroplast) and substrate level phosphorylation (in intermediate steps of metabolic pathway). As soon as ATP is synthesized, it hydrolyzed to release free energy that drives cellular chemical reactions.

ATP + H₂O → ADP + Pi + Energy (8.9 Kcal)

ADP + H₂O → AMP + PPi + Energy (6.5 Kcal)

The Pi and PPi are called orthophosphate (PO₄^3-) and pyrophosphate (P₂O₇^4-) respectively. The hydrolysis of terminal phosphoanhydride bond release 8.9 Kcal/mole (older estimate 7.3 Kcal/mole) while the second phosphoanhydride bond release 6.5 Kcal/mole (older estimate 7.3 Kcal/mole).

Functioning of Nucleotides:

1. Nucleotides are the basic units of nucleic acids (DNA and RNA). Though, nucleoside monophosphates found in nucleic acids, actually nucleoside triphosphates are the raw materials for their synthesis.

2. Cyclic Nucleotides Act as Regulatory Chemicals. Cyclic AMP (cAMP) functions as second messengers in many hormone actions, while cyclic GMP (cGMP) functions in Ca⁺⁺ or calmodulin mediated responses.

3. Nucleotides of B-Complex Vitamins Function as Coenzymes. For example, NAD⁺, NADP⁺, FMN, FAD are coenzymes useful in oxidation-reduction reactions.

4. Higher nucleotides function as energy carriers, e.g. ATP GTR UTP and TTP Out of these ATP is the universal energy carrier of the cell.

5. Higher nucleotides involved in the synthesis of polysaccharides (e.g. UDP-glucose, ADP-glucose) and phospholipids (e.g. CDP and CTP).

Formation of Polynucleotide:

The nucleotides undergo the process of polymerization to form a long chain of polynucleotide. A phosphodiester bond joins pentose sugar with phosphoric acid. The nucleotides are designated by prefixing ‘poly’ to each repeating unit such as poly A (polyadenylic acid), Poly T (polythymidilic acid), poly G (polyguanidylic acid), poly C (polycytidilic acid) and poly U (polyuridylic acid). The polynucleotides that consist of the same repeating units are called homopolynucleotides such as poly A, poly T, poly G, poly C and poly U.