6) Nucleic Acids

• All cells contain 2 types of nucleic acids:

  • Deoxyribonucleic acids (DNA): genetic material of the cell
  • Ribonucleic acids (RNA): contributes to protein synthesis
  • Both are macromolecules, polymers of nucleotide monomers
• Nucleotides consist of:

  • Pentose sugar (5 carbon sugar)
  • Phosphate group (-ve charged, attached to carbon 5' of the sugar)
  • Nitrogenous base (attached to carbon 1' of the sugar)
  • Purines (Adenine & Guanine with 2 rings)
  • Pyrimidines (Cytosine, Thymine - in DNA, Uracil - in RNA)
• Thymine is found only in DNA, while uracil is found only in RNA
• Nucleotides polymerize by forming phosphodiester bonds between carbon 3' of the sugar and an oxygen atom of the phosphate group in a condensation reaction
• DNA:

  • Contains deoxyribose sugar and bases (A, G, C, T)
  • Double-stranded structure made of 2 polynucleotide chains running in opposite directions (Antiparallel)
  • Strands joined by hydrogen bonds between nitrogenous bases forming base pairs according to complementary base pairing rule
• DNA replication occurs in the S phase of interphase to ensure daughter cells receive a copy of the parent cell's DNA
• DNA replication process:

  1. Free nucleotides in nucleoplasm are activated by attaching 2 phosphate groups

  2. DNA unwinds & unzips with helicase breaking hydrogen bonds between bases

  3. DNA polymerase synthesizes a new strand following the complementary base pairing rule

  4. Leading strand replicated continuously, lagging strand in segments joined by DNA Ligase forming Okazaki fragments

  5. Replication is semiconservative, with each new DNA molecule having one old strand conserved from the parent cell
• Proof of Semiconservative Replication:

  • E.coli bacteria grown in N15 then transferred to N14 to track DNA replication
• DNA vs. RNA:

  • DNA: double-stranded, thymine base, deoxyribose sugar, larger molecule, very stable
  • RNA: single-stranded, uracil base, ribose sugar, smaller molecule, less stable
• Types of RNA:

  1. Messenger RNA: carries message from DNA to ribosomes for protein synthesis

  2. Ribosomal RNA: combines with proteins to form ribosomes

  3. Transfer RNA: transfers amino acids to ribosomes for protein synthesis
• DNA controls protein structure by determining the sequence of amino acids, acting as a code for proteins and controlling the cell's activities
• Transcription process:

  1. DNA unwinds & unzips, RNA Polymerase binds to template strand

  2. RNA Polymerase pairs free activated RNA nucleotides with exposed bases on the sense strand

  3. RNA polymerase joins nucleotides by phosphodiester bonds

  4. Process continues until a stop triplet is reached, mRNA undergoes post-transcriptional modification to form mature mRNA
• In eukaryotes, mRNA is modified before leaving the nucleus. The original molecule is called the primary transcript. The process of modification is RNA processing, which includes RNA splicing.

  • RNA splicing is the removal of sections of the primary transcript by spliceosomes (RNA + Proteins).
  • Splicing cuts the RNA, removing non-coding sections called introns.
  • It leaves the coding sections of RNA, called exons, which are joined together after introns are removed.
• Debate surrounds the functions of introns. They can help regulate gene activity and allow for alternative splicing, where a primary transcript can be spliced in different ways. This results in different mRNAs and ultimately different proteins being produced.
• Translation is the process where mRNA codons are translated into a sequence of amino acids in a polypeptide chain.

  • In the cytoplasm, free tRNA molecules with anticodons bind to specific amino acids.
  • mRNA binds to the ribosome, exposing codons to tRNA molecules.
  • Peptide bonds form between amino acids, catalyzed by peptidyl transferase enzyme.
  • The ribosome moves along the mRNA, translating codons until a stop codon is reached, terminating translation.
• A mutation is a change in the DNA nucleotide sequence that alters the codon sequence in mRNA during transcription. This leads to different tRNA binding during translation, changing the primary structure of the resulting protein.
• Sickle Cell Anemia is an inherited disease resulting from a mutation in the gene coding for the 𝛽 chain of hemoglobin.

  • The mutation changes the base triplet from CTT (glutamate) to CAT (valine), causing the distorted tertiary structure of hemoglobin.
  • The hydrophobic valine makes hemoglobin water-insoluble, leading to the sickle shape of red blood cells and impaired oxygen transport.
• Nucleic acids play crucial roles in storing and retrieving genetic information and synthesizing polypeptides. DNA is the hereditary molecule, replicated accurately in cells. The genetic code determines the amino acid sequence in polypeptides based on DNA and mRNA nucleotide sequences.
• Protein synthesis involves transcription and translation processes to construct polypeptides.

  • Transcription uses RNA polymerase to transcribe DNA into mRNA.
  • mRNA carries codons that correspond to specific amino acids.
  • Translation involves ribosomes, tRNA with anticodons, and amino acids binding to form polypeptides.
• Gene mutations are changes in DNA base pairs that can alter polypeptides.

  • Mutations can be substitutions, deletions, or insertions of nucleotides, affecting the resulting polypeptide structure.