Like the proteins, the nucleic acids are biopolymers with mononucleotide as their repeating units, just as amino acids are the repeating units of proteins. Nucleic acids consist of a nitrogenous base, a sugar and a phosphate residue. We will now discuss the component of nucleotide sequentially for better concepts and understanding.
Table of Contents
- A 5-carbon keto sugar pentose sugar which is ribose is one of the important component of the nucleotide.
- Although, there are other pentoses but ribose is selected in nucleic acid, because it gets best fitted and prevents any kind of stearic clash or interference with the bulky base.
- Sugars in both DNA and RNA are present in the furanose form and are of β configuration.
- Interestingly, the two types of nucleic acids (DNA and RNA) are mainly distinguished on the basis of pentose which they possess. DNA possesses β D-2-deoxyribose (OH group on C-2’ has been replaced by an H atom), hence the name deoxyribose nucleic acid or deoxyribonucleic acid, while the RNA contains D-ribose (OH group on C-2’ present), hence the name ribose nucleic acid or ribonucleic acid.
- An important property of the pentoses is their capacity to form esters with phosphoric acid. In the reaction given below the OH groups of the pentose, especially those at C3 and C5, are involved forming a 3′, 5′- phosphodiester bond between adjacent pentose residues.
Why DNA is primarily selected as a genetic material over RNA?
Well known fact is that for the genetic material the DNA is selected over RNA. This is so because of:-
- The presence of 2’-OH group in ribose of RNA, is positioned such that it can easily cleave the RNA backbone by intramolecular attack on the phosphate of the phosphodiester bond (figure below). The products formed after these cleavage reactions are a free 5’-OH and a 2, 3-cyclic phosphodiester, which is subsequently hydrolyzed to either the 2- or 3-monophosphate.
- Even at neutral pH, RNA is much more susceptible to hydrolysis.
- Thus, RNA is a short term molecule needed for carrying information and OH group in 2’ of RNA makes this more reactive towards molecular signals and thus can readily regulated by post transcriptionally.
On the other hand the DNA lacks the 2’-OH group in ribose that makes DNA extremely highly stable.
- The base is linked to the pentose sugar by the carbon-1 (C1).
- Four nitrogenous bases present in DNA are adenine, guanine, cytosine and thymine,and are grouped into two categories; purine and pyrimidine.
- Two purine bases i.e. adenine and guanine have a double ring structure and the pyrimidine bases i.e. cytosine and thymine have a single ring structure.
- Owing to their π electron clouds, both the pyrimidine and purine bases are planar molecules.
- These are derived from their parent heterocyclic compound pyrimidine.
- Pyrimidine contains a six membered ring with two-nitrogen atoms and three double bonds.
- Common pyrimidines are uracil, thymine and cytosine.
- Purine derivatives are derived from their parent compound purine, which contains a six-membered pyrimidine ring fused to the five-membered imidazole ring.
- Common purines are adenine and guanine.
Modified Nitrogenous Bases
There are some modified nitrogenous bases that occur in polynucleotide structures and represented in figure below.
Tautomerism in Nitrogenous Bases
- The four bases in the DNA can spontaneously undergo transient rearrangement of bonding that is termed as tautomeric shift, forming a structural isomer.
- This change results in the alteration of base pairing properties of the base. The base can change from their normal amino (NH2) form to imino (NH) form or from usual keto (C=O) to enol (C-OH) form.
- Also, the tautomer containing the carbonyl group (= CO) is designated as the keto or lactam form and the other one having a hydroxy group (—OH) attached to a doubly-bonded carbon is referred to as the enol or lactim form.
This kind of tautomerism is called keto-enol or more appropriately lactam-lactim tautomerism.
However, it is the keto (= lactam) form which predominates at neutral and acid pH values which are of physiological importance; the enol (= lactim) form becomes more prominent as pH decreases (i.e., at acidic values).
The molecular formula of phosphoric acid is H3PO4. It contains 3 monovalent hydroxyl groups and a divalent oxygen atom, all linked to the pentavalent phosphorus atom.
When a base is joined to sugar by a β-glycosidic linkage, the molecule is called a nucleoside. Formation of the the β-glycosidic linkage involves the reaction between the C-1′ of sugar and the hydrogen atom of N-9 (if purines) or N-1 (if pyrimidines), thus removing a molecule of water.
Therefore, the purine nucleosides are N-9 glycosides and the pyrimidine nucleosides are N-1 glycosides.
- Nucleotides are the phosphoric acid esters of nucleosides.
- Thus, in a nucleotide the base (purine or pyrimidine) is joined to 1’ carbon of pentose by an N-β- glycosyl bond and a phosphate is esterified to 5’ carbon.
- Phosphate of 5’ carbon reacts with –OH group which is attached to 3’ ribose sugar carbon and this fifth carbon atom is always outside the ring. During this bond formation a water molecule is removed.
- It is the phosphate group that connects two sugar molecules together. For this reason, the linkage in DNA strands is referred to as phosphodiester linkage.
- In fact, the backbone of a DNA strand is formed by sugar and phosphate group. There are two ester (C-O-P) bonds in each linkage. Precisely it is referred to as 3′-5′ phosphodiester bond. But single nucleotide has no phosphodiester linkage.
Upto three individual phosphate groups can be attached in series giving a nucleoside monophosphate (NMP), nucleoside diphosphate (NDP) and nucleoside triphosphate (NTP). These individual phosphate groups are designated as α, β, and γ. The α-phosphate group is the one directly attached to the sugar. Deoxyadenosine monophosphate (dAMP), deoxythymidine monophosphate (dTMP), deoxycytidine monophosphate (dCMP) and deoxyguanosine monophosphate (dGMP).
- The hydrolysis of ATP and other nucleoside triphosphates is an exergonic reaction.
- The bond between the ribose and the α-phosphate is an ester linkage.
- The α-β and β-γ linkages are phosphoric acid anhydrides.
- Hydrolysis of the ester linkage yields about 14 kJ/mol, whereas hydrolysis of each of the anhydride bond yields about 30 kJ/ mol.
- In biosynthesis, ATP hydrolysis often drives less favourable metabolic reactions (i.e., those with ΔG°′ > 0).
- When coupled to a reaction with a positive free-energy change, ATP hydrolysis shifts the equilibrium of the overall process to favour product formation.
- The individual nucleotides are joined together to form a polymer, called polynucleotide.
- For polynucleotide formation the nucleotides are bonded together by joining the α-phosphate group, attached to 5′-carbon of one nucleotide, to the 3′- carbon of the next nucleotide in the chain.
- Normally a polynucleotide is build up from nucleoside triphosphate subunits, so during polymerization the β- and γ-phosphate are removed. The hydroxyl group attached to 3′-carbon of the second nucleotide is also lost.
- There are two ends of the polynucleotide. 5′-carbons is at one end and not participate in a phosphodiester bond and β- and γ- phosphates are also attached. This end is called 5′ or 5′-P terminus.
- The other end is 3′-hydroxyl which has unreacted hydroxyl group. This end is called the 3′ or 3-OH terminus. Due to this, the polynucleotides have a direction which can be 5′-3′ (down) or 3′-5′ (up).