RJAV - Biochemistry

• Biochemistry


  Deals with the physical and chemical properties of compounds that make up the smallest unit of life and how these compounds undergo processes and relate it with how it affects the daily function of human beings
• Key molecules


  • Proteins
  • Carbohydrates
  • Lipids
  • Nucleic Acids
  • Water
• Proteins


  Constitute 70% of the organic matter of cell. The simplest unit is amino acid, and proteins are polymers of these repeating units linked together
• Amino acids


  Organic molecules containing both carboxyl and amino functional groups

  
• There are about 300 amino acids occurring in nature, but only about 20 are commonly occurring and are constituents of proteins. Except for proline, an imino acid, all 19 are alpha amino acid
• Amino acids with non-polar R-groups


  • Alanine
  • Valine
  • Leucine
  • Isoleucine
  • Proline
  • Phenylalanine
  • Tryptophan
  • Methionine
• Amino acids with uncharged polar groups


  • Glycine
  • Serine
  • Threonine
  • Tyrosine
  • Asparagine
  • Glutamine
  • Cysteine
• Amino acids with charged polar groups


  • Glutamic Acid
  • Aspartic Acid
  • Lysine
  • Histidine
  • Arginine
• Levels of protein structure


  • Primary
  • Secondary
  • Tertiary
  • Quaternary
• Primary structure


  The simplest level of structural organization composed of the amino acid resides linked through peptide bonds

  
• Primary structure


  • The sequence is written from left to right (N–Terminal to C–Terminal amino acid)
  • In an electric field, positively charged proteins move towards the cathode (-), negatively charged proteins move towards the anode (+), and proteins at the isoelectric pH have no migration since net charge is 0
• Secondary structure


  • α-Helix: A helical configuration of the polypeptide chain formed by the Hydrogen bonding between the peptide groups of every first and fourth AA residues
  • β-Sheets: Pleated sheet structure resembling an accordion, can be in a form of a parallel or an antiparallel chain

  
• Secondary structure examples


  • Keratin
  • Collagen
  • Fibroin
• Creutzfeldt-Jakob Disease


  Caused by the transmission of Prions (a proteinaceous infectious agent that causes neurodegenerative diseases) that results to the misfolding of the normal prion protein found abundantly in the brain, causing replacement of the normal α-helical arrangement with β-pleated sheet, leading to dementia and involuntary jerking movements (startle myoclonus)
• Tertiary structure


  Refers to the spatial arrangement of the polypeptide chain, can either be Fibrous or Globular, stabilized by covalent bonds, polar bonds, and non-polar/van der-Waals interactions
• Chaperones


  Proteins that assist in the folding and unfolding of the polypeptide to correctly form the tertiary structure, example: Heat Shock Proteins
• Quaternary structure


  Spatial arrangement of proteins made up of several polypeptide chains, with each peptide chain having a tertiary structure, referred to as Oligomers
• Denaturation


  Destruction of the higher structural levels of protein without destroying the peptide bonds, caused by agents such as heat and urea
• Renaturation


  Recovery of the protein from its denatured state
• Medically important proteins


  • Hemoglobin
  • Collagen
  • Insulin
• Hemoglobin


  Globular transport protein for oxygen, contains heme which is a complex of porphyrin ring and a ferrous
• Sickle cell anemia


  Caused by a mutation in hemoglobin where the glutamate at position six in the beta–chain is replaced by valine, has higher affinity to CO than CO2
• Collagen


  Found mainly in the bones and cartilage, mainly contains glycine, proline, hydroxyproline. Types include I, II, III, IV, V
• Osteogenesis imperfecta


  A disorder in the synthesis of Type I collagen characterized by a distinctive blue sclera and predisposed multiple childhood fracture
• Ehlers-Danlos syndrome


  A group of connective tissue disorders generally characterized by hyperextensible skin, joint hypermobility, and defects in large blood vessels
• Insulin


  A polypeptide hormone produced by the beta – cells of the pancreas, synthesized from preproinsulin to proinsulin to insulin
• Qualitative tests for proteins and amino acids


  • Biuret test
  • Ninhydrin test
  • Xanthoproteic test
  • Millon's test
  • Hopkin's-Cole test
  • Nitroprusside test
  • Sakaguchi test
• Enzymes


  Biological catalysts of protein nature which catalyze energetically feasible reactions without altering the reaction route, highly specific for their substrates and products, velocity of reaction is directly proportional to temperature but degrade at temperatures higher than 37°C, changes in pH can cause denaturation
• Enzyme nomenclature


  • Oxidoreductases
  • Transferases
  • Hydrolases
  • Lyases
  • Isomerases
  • Ligases
• Enzyme inhibition


  • Competitive
  • Noncompetitive
  • Irreversible
• Isoenzymes


  Enzymes that may differ in amino sequences and physical properties but catalyze the same reaction
• DNA structure


  Contains nucleosides made up of a nitrogenous base, deoxyribose, and phosphate, with purines (adenine, guanine) and pyrimidines (cytosine, thymine)

  
• DNA double helix


  Proposed by Watson and Crick, formed by the pairing of two antiparallel polynucleotide chains with complementary base sequences (adenine-thymine, guanine-cytosine), one full turn contains 10 nucleotides
• DNA conformations


  B form: Right-handed

  Z form: Left-handed

  A form: Dehydrated and compact, right-handed
• Denaturation


  Separation of the DNA strands due to heat or alkali exposure without breaking the phosphodiester bond
• Renaturation


  Upon heating, DNA strands separate but the base pairs reform once the temperature is slowly decreased
• Hybridization


  A single strand of DNA or RNA pairs with a complementary base sequence on another strand of DNA or RNA
• Histones


  Small, basic proteins rich in arginine and lysine that DNA is complexed with in eukaryotic chromatin, not present in prokaryotes
• Differences between RNA and DNA


  • RNA contains ribose instead of deoxyribose, uracil replaces thymine, is single-stranded with extensive base pairing, and can sometimes act as catalysts and enzymes
• Types of RNA


  • Messenger (mRNA)

  Ribosomal (rRNA)

  Transfer (tRNA)