Nucleotides: Meaning and Functions

In this article we will discuss about the meaning and functions of Nucleotides.

Meaning of Nucleotides:

Nucleotides are basic units of nucleic acids. They also form energy carriers. Certain nucleotides act as coenzymes. Some nucleotides function as chemical messengers. A nucleotide is a condensation product of three chemicals— a pentose sugar, phosphoric acid and a nitrogen base.

Two types of pentose sugars occur in nucleotides— ribose (C₅H₁₀O₅) and deoxyribose (C₅H₁₀O₄). Both of them occur in furanose state or pentagon ring with one oxygen and four carbon atoms. The fifth carbon having —CH₂OH complement lies outside the ring. Carbon atom 2 contains two hydrogen atoms in deoxyribose.

It is hence called 2′ deoxyribose. Ribose differs from deoxyribose in having a hydroxyl (—OH) group instead of a second hydrogen at carbon 5. Deoxyribose occurs only in those nucleotides which make up the hereditary material DNA. Ribose is found in nucleotides forming RNA and a number of other compounds like AMP, ATP, NAD, NADP, FAD, CoA, etc.

Nitrogen bases are heterocyclic compounds. They are of two types, substituted, purines and substituted pyrimidine’s. Pyrimidine’s are 6-membered rings while purines are 9- membered double rings.

A pyrimidine ring has nitrogen at 1 and 3 positions, A purine has imidazole ring joined to pyrimidine ring at 4 and 5 positions. It has nitrogen’s at 1, 3, 7 and 9 positions. There are two types of purines— adenine (A) and guanine (G). Pyrimidine bases are of three types— cytosine (C), thymine (T) and uracil (U).

A combination of a nitrogen base with a pentose sugar is known as nucleoside. The nitrogen base combines with the sugar molecule at its carbon atom 1 in a glycosidic bond (C-N-C) by one of its nitrogen atoms (usually 1 in pyrimidine’s and 9 in purines). Depending upon the type of pentose sugar, nucleosides are differentiated into ribonucleosides and deoxyribonucleosides.

Uracil produces nucleoside with only ribose sugars. Thymine simi­larly forms nucleoside with only deoxyribose sugar. Other nitrogen bases produce nucleo­sides with both ribose and deoxyribose sugars.

The different nucleosides are adenosine (adenine +ribose), deoxyadenosine (adenine + deoxyribose), guanosine (guanine + ribose), deoxyguanosine (guanine + deoxyribose), uridine (uracil + ribose), deoxythymidine (thymine + deoxyribose), cytidine (cytosine + ribose), deoxycytidine (cytosine + deoxyribose).

Nucleotides are phosphoric acid esters of nucleosides. Phosphate combines with sugar molecule at its 5′ carbon atom. However, phosphate linked to У carbon atom and rarely 2 carbon atom is also known.

The number of phosphoric or phosphate residues may be up to three in free occurring nucleotides. On the basis of pentose sugar present, nucleotides are distinguished into ribonucleotides (= ribotides) and deoxyribonucleotides (= deoxyribotides). Being phosphorylated form of nucleosides, they are also called nucleoside phosphates.

The various nucleotides are adenylic acid (adenosine monophosphate or AMP), deoxyadenylic acid (dAMP), guanylic acid (guanosine monophosphate or GMP), deoxyguanylic acid (dGMP), uridylic acid (uridine monophosphate or UMP), deoxythymidylic acid (deoxythymidine mono­phosphate or dTMP), cytidylic acid (cytidine monophosphate or CMP) and deoxycytidylic acid (dCMP).

Higher Nucleotides:

Nucleotides having more than one phosphate group are called higher nucleotides. Higher nucleotides occur in the Free State. The second and third phosphates of higher nucleotides are attached against forces of repulsion be­tween similarly charged phosphate radicals. Hence, the bonds attaching second and third phosphates are high energy bonds, much higher than com­mon covalent bonds.

A number of higher nucleotides are known— GDP, GTP (guanosine triphosphate), CDP, CTP (cytidine triphosphate), UDP, UTP (uridine triphosphate), ADP (adenosine diphosphate) and ATP (adenosine triphosphate). Out of these ADP and ATP are well known. Due to the presence of high energy bonds, higher nucleotides function as energy carriers.

ATP:

It is adenosine triphosphate. Adenosine triphosphate is formed of an adenine (a purine), a ribose (pentose sugar) and a row of three phosphate radicals attached to ribose. The complex formed by adenine and ribose is called adenosine. ATP or adenosine triphos­phate (Fig. 9.19). was discovered by Karl Lohmann in 1929 from muscles.

Its functioning was found out by Fritz Lipmann (1941). Lipmann is also called father of ATP cycle. The second and third phosphates of ATP are attached by high energy bonds. The bonds have high transfer potential because they are held against great elec­trostatic repulsion.

ADP + Pi + Energy ↔ATP reaction can occur in a cyclic manner of build up and break­down reactions. It is an instant store house as well as source of energy. ATP is found in all living cells. It is also mobile within the cell.

Therefore, ATP can pick up energy where it is being liberated and supply the same where it being consumed. ATP is called universal energy carrier as well as energy currency of the cell. ATP usually obtains energy during respiration.

It provides energy to cellular constitu­ents for overcoming entropy and carrying out various activities like membrane transport, nerve conduction, muscle contraction, biosynthesis, microtubule synthesis, cytoplasmic streaming, cell movement, cell division, osmosis, heat, etc.

The last phosphate bond is easily built up and broken for this purpose (Fig. 9.20). The enzyme is ATP-ase. Breakage of this bond releases 8.9 Kcal (8900 calories) per mole (older estimate 7.3 kcal/mole). Similar amount of energy is required for its building. The second energy rich bond has an energy equivalent of 6.5 Kcal per mole.

Nucleotides of Vitamins (Coenzymes):

Nicotinamide and flavin parts of riboflavin, two В-complex vitamins, function as nitro­gen bases. Singly or in combination with other nucleotides, they produce important coen­zymes (Table 9.3) which take part in oxidation-reduction reactions.

These coenzymes are NAD⁺ (Nicotinamide adenine dinucleotide), NADP+ (Nicotinamide adenine dinucleotide phos­phate), FMN (Flavin mononucleotide) and FAD (Flavin adenine dinucleotide). Another nucle­otide of vitamin is coenzyme A. It consists of adenine, ribose, 3 phosphates, pantothenic acid and mercaptoethylamine. CoA functions as acyl group carrier, e.g., Acetyl CoA.

They may occur in the Free State but are biologically active in contact with specific Apo enzymes. The enzymes formed from them are dehydrogenases. The coenzymes oxidize different chemicals by removing hydrogen from them. The reduced coenzymes hand over their hydrogen to other chemicals.

NAD⁺/NADP⁺ + 2H ↔ NADH/NADPH + H⁺

FMN/FAD +2H ↔ FMNH₂/FADH₂

Functions of Nucleotides:

1. They are building blocks of nucleic acids, ribonucleotides for RNAs while deoxyribonucleotides produce DNA.

2. Cyclic AMP (cAMP) functions as second chemical messenger in many hormone controlled chemical reactions.

3. Cyclic GMP (cGMP) is functional in Ca²⁺ or calmodulin mediated chemical reaction.

4. Higher nucleotides behave as energy carriers. ATP is known as energy currency of the cell since it contains high energy phosphate bonds which are built up when energy is available and broken down when energy is to be utilized.

5. Nucleotides produced by nicotinamide and riboflavin function as coeyzymes (NAD⁺, NADP⁺, FMN and FAD) of deydrogenases or oxidases.

6. CoA is produced by reaction between nucleotide and pantothenic acid.

7. UDP and ADP are involved in synthesis of polysaccharides while CDP and CTP are required in phospholipid synthesis.