Nucleic acid

• Nucleic acids


  Found in the nucleus of cells, concerned with the storage and transfer of genetic information
• Types of nucleic acids

  • Deoxyribonucleic acid (DNA)
  • Ribonucleic acid (RNA)

  
• Nucleotides


  Precursors (building blocks) of nucleic acids, also components of coenzymes and metabolic regulators
• Components of nucleotides


  • Nitrogenous base (Purine or Pyrimidine)
  • Pentose sugar (ribose or deoxyribose)
  • Phosphate groups
• Nucleoside


  Base + sugar
• Nucleotide


  Nucleoside + phosphate group
• Purine bases


  • Adenine
  • Guanine

  
• Pyrimidine bases


  • Cytosine
  • Thymine
  • Uracil

  
• Pentose sugar in nucleic acids

  1. ribose in RNA, 2-deoxy-D-ribose in DNA

  
• Formation of nucleotides


  1. Base + sugar = nucleoside

  2. Nucleoside + phosphate group = nucleotide
• DNA and RNA are polymers of nucleoside monophosphates

  
• Nucleoside di and triphosphates have high energy bonds, e.g. ATP is the universal energy currency of the cell
• Phosphodiester bond/linkage


  Formed between 3' and 5' of ribose group, forming cyclic nucleotides like cAMP and cGMP which function as metabolic regulators and second messengers
• Deoxyribonucleotides polymerise to form DNA, ribonucleotides form RNA

  
• Some bases and nucleotides are used as anti-cancer and anti-viral drugs
• Deoxyribonucleotides in DNA


  • Deoxyadenylate (A)
  • Deoxyguanylate (G)
  • Deoxycytidylate (C)
  • Deoxythymidylate (T)

  
• Phosphodiester bond in DNA

  The 5' OH group on one sugar is combined with 3' OH group of another sugar through a phosphate group
• The base sequence in DNA is very important as it codes the genetic information

  
• The sequence of DNA is written from 5' to 3' end, this is called the polarity of DNA chain/strand

  
• Watson-Crick model of DNA structure

  • Right-handed double helix
  • Base pairing rule (A-T, G-C)
  • Hydrogen bonding between bases
  • Antiparallel strands
  • Conservative replication

  
• Denaturation of DNA


  The double stranded DNA molecule may be separated by heat, this is called melting of DNA
• There are three structural forms of DNA: A-form, B-form, Z-form
• Functions of DNA


  • Replication in dividing cells
  • Carrying information for protein synthesis
• Higher organisation of DNA

  • Wound over histones to form nucleosomes, which are condensed into chromatin
  • Chromatin further condensed and folded to form chromosomes
  • Transcriptionally active regions are euchromatin, inactive regions are heterochromatin

  
• All human cells contain the same genetic information as they are derived from the zygote
• Only about 10% of human DNA contain genes, the rest is permanently inactive
• Cistron


  The unit of genetic expression, the biochemical counterpart of a gene

  
• Differences between RNA and DNA

  • Mainly in cytoplasm vs mostly in nucleus
  • Generally single stranded vs double stranded
  • Sugar is ribose vs deoxyribose
  • Purines are A, G vs A, G
  • Pyrimidines are C, U vs C, T
  • G-C, A-T bonds vs G=C, A=T
  • Easily destroyed by alkali vs alkali resistant

  
• Types of cellular RNA

  • Messenger RNA (mRNA)
  • Heterogenous Nuclear RNA (hnRNA)
  • Transfer RNA (tRNA)
  • Ribosomal RNA (rRNA)
  • Small Nuclear RNA (snRNA)
• The main function of RNA is to make proteins after taking instructions from the DNA
• Ribosomes


  Large complexes of proteins and ribosomal RNA, where protein synthesis takes place
• Ribosome subunits


  • Prokaryote: 50S + 30S = 70S
  • Eukaryote: 60S + 40S = 80S
• Ribosome structure and function

  • Ribosomal proteins play roles in structure and function
  • Has 3 binding sites for tRNA (A, P, E sites)
  • Free in cytosol or associated with ER (rough ER)
• Haemoglobin


  Found exclusively in RBCs, may function to transport oxygen (O2) from the lungs to the capillaries of tissues

  
• Haemoglobin A (major haemoglobin in adults)

  • Has 4 peptide chains; 2α and 2β chains held together by noncovalent interactions
  • Each subunit has stretches of α-helical structure and a heme-binding pocket

  
• Quarternary structure of haemoglobin

  Haemoglobin tetramer is made up of 2 identical dimers (αβ)1 and (αβ)2

  
• Structure of haemoglobin dimers

  • The 2 peptide chains within each dimer are held tightly together primarily by hydrophobic interactions, ionic and H-bonds also occur (between α and β chains)
  • The 2 dimers held together by polar bonds are able to move w. r. t. each other, these weaker interactions result in the 2 dimers occupying different relative positions in deoxyhaemoglobin as of oxyhaemoglobin
• Deoxy form of haemoglobin (T-form)

  The low oxygen-affinity form, where the αβ dimers interact through a network of ionic bonds and H-bonds that constrain the movement of the peptide chains

  
• Oxy form of haemoglobin (R-form)


  The high oxygen-affinity form, where the binding of O2 causes the rupture of some ionic and H-bonds between the αβ dimers, leading to a relaxed structure with more freedom of movement

  
• Oxygen binding to haemoglobin

  • Haemoglobin can bind 4 oxygen molecules, one to each of its heme groups
  • The degree of saturation (Y) of the oxygen binding sites can vary between zero and 100%
  • The partial pressure of oxygen needed to achieve half-saturation of the binding sites (P50) is approximately 26mmHg for hemoglobin