Detailed Notes on Nucleic Acid Structure and Composition

Introduction to Nucleic Acids

  • Nucleic acids are defined as large molecules located within the nuclei of cells in the human body.
  • Their primary functions involve:
    • Storing genetic information.
    • Directing cellular activities necessary for growth and reproduction.
  • There are two closely related types of nucleic acids:
    • Deoxyribonucleic acid (DNA).
    • Ribonucleic acid (RNA).
  • Both DNA and RNA are categorized as unbranched polymers composed of repeating monomer units called nucleotides.
  • Scale comparison of nucleic acids:
    • A DNA molecule can contain several million nucleotides.
    • Smaller RNA molecules may contain up to several thousand nucleotides.

Chemical Components of Nucleotides

  • Each individual nucleotide is composed of three distinct components:
    1. A nitrogen-containing base.
    2. A five-carbon (pentose) sugar.
    3. A phosphate group.

Nitrogen-Containing Bases: Purines and Pyrimidines

  • The bases found in nucleic acids are chemical derivatives of either pyrimidine or purine.
  • Purines (Double Rings):
    • Adenine (A)
    • Guanine (G)
    • Both Adenine and Guanine are found in DNA and RNA.
  • Pyrimidines (Single Rings):
    • Cytosine (C): Found in both DNA and RNA.
    • Thymine (T): Found in DNA only. Chemically known as 5-methyluracil5\text{-methyluracil}.
    • Uracil (U): Found in RNA only.
  • In RNA, the base uracil replaces the thymine found in DNA.

Pentose Sugars: Ribose and Deoxyribose

  • Ribose: The five-carbon sugar in RNA, which provides the "R" in the abbreviation RNA.
  • Deoxyribose: The five-carbon sugar in DNA, providing the "D" in the abbreviation DNA.
  • Structural Differences:
    • Deoxyribose is structurally similar to ribose except that there is no hydroxyl group (−OH-OH) on the second carbon (C2′C2').
    • The prefix "deoxy-" literally signifies "without oxygen."
  • Atom Numbering: Atoms in the pentose sugars are numbered with primes (1′1', 2′2', 3′3', 4′4', and 5′5') to distinguish them from the atoms in the nitrogenous bases.

Formation of Nucleosides and Nucleotides

  • Nucleosides:
    • A nucleoside is a combination of a sugar and a base.
    • It is produced when a nitrogen atom in a purine or pyrimidine base forms an N-glycosidic bond to carbon 11 (C1′C1') of a ribose or deoxyribose sugar.
    • Example: Adenine combined with ribose forms the nucleoside adenosine.
  • Nucleotides:
    • Nucleotides are nucleosides in which a phosphate group bonds to the hydroxyl group (−OH-OH) on carbon 55 (C5′C5') of the pentose sugar.
    • This chemical bond results in a phosphate ester.
    • While other hydroxyl groups on the ribose sugar can form phosphate esters, only the 5′-monophosphate5'\text{-monophosphate} nucleotides are found in RNA and DNA.

Naming and Abbreviations of Nucleosides and Nucleotides

  • Naming Suffixes:
    • Nucleosides containing a purine base end in -osine.
    • Nucleosides containing a pyrimidine base end in -idine.
  • DNA Naming: The names of nucleosides in DNA include the prefix "deoxy-".
  • Nucleotide Naming: Corresponding nucleotides are named by adding 5′-monophosphate5'\text{-monophosphate} to the nucleoside name.
  • Abbreviations: While the letters A, G, C, U, and T represent the bases, they are also used as shorthand for the respective nucleosides and nucleotides.
Summary Table for DNA
BaseNucleosideNucleotide
Adenine (A)Deoxyadenosine (A)Deoxyadenosine-5'-monophosphate (dAMP)
Guanine (G)Deoxyguanosine (G)Deoxyguanosine-5'-monophosphate (dGMP)
Cytosine (C)Deoxycytidine (C)Deoxycytidine-5'-monophosphate (dCMP)
Thymine (T)Deoxythymidine (T)Deoxythymidine-5'-monophosphate (dTMP)
Summary Table for RNA
BaseNucleosideNucleotide
Adenine (A)Adenosine (A)Adenosine-5'-monophosphate (AMP)
Guanine (G)Guanosine (G)Guanosine-5'-monophosphate (GMP)
Cytosine (C)Cytidine (C)Cytidine-5'-monophosphate (CMP)
Uracil (U)Uridine (U)Uridine-5'-monophosphate (UMP)

Primary Structure and the Phosphodiester Backbone

  • The Phosphodiester Bond:
    • Nucleic acids are polymers where the 3′-OH3'\text{-OH} group of the sugar in one nucleotide bonds to the phosphate group on the 5′-carbon5'\text{-carbon} atom of the sugar in the subsequent nucleotide.
    • This phosphate linkage between adjacent sugars is called a phosphodiester bond (specifically a 3′−5′3'-5' phosphodiester bond).
  • Primary Structure:
    • Each nucleic acid has a unique sequence of bases, known as its primary structure.
    • The sequence of bases carries genetic information from one cell to the next.
    • The nitrogenous bases extend outward from the sugar-phosphate backbone.
  • Directionality and Reading:
    • One end has an unreacted or free 5′-phosphate5'\text{-phosphate} terminal.
    • The other end has a free 3′-hydroxyl3'\text{-hydroxyl} group.
    • Nucleic acid sequences are always read from the free 5′5' end to the free 3′3' end.
    • Sequences are often written using base abbreviations. For example, an RNA section starting with adenine (at the 5′5' end) followed by cytosine, guanine, and uracil is written as: 5′-A-C-G-U-3’5'\text{-A-C-G-U-3'}.

References

  • 1. Lehinger principles of biochemistry, 5th edition.
  • 2. W.H. Freeman and company harpers illustrated biochemistry, 28th edition.
  • 3. An introduction to general, organic and biological chemistry by Timberlake, 11th edition.