BMSC200 MODULE 1

• Biochemistry


  • The study of life at the molecular level
  • The application of the principles of chemistry to explain biology
  • The common sets of reactions and principles that underlie all living organisms
  • The study of the molecular logic of life
• In spite of considerable differences in their size and complexity, all living organisms are remarkably uniform at the molecular level
• • All organisms use a common repertoire of building blocks to create common categories of biomolecules (nucleic acids, proteins, polysaccharides, and lipids)
  • All organisms use a common core of essential biochemical processes
• Jacques Monod: 'Anything found to be true of E. coli must also be true of elephants'
• The Foundations of Life

  • Chemical
  • Energy
  • Genetic
  • Evolutionary
• Chemical Foundations


  • All living things are made from simple and common ingredients
  • Four elements (carbon, oxygen, hydrogen, and nitrogen) account for 98% of most organisms
  • All known life forms are carbon based
• • Air contains lots of nitrogen but in an inert form (N2)
  • Ultimately, nitrogen within the biosphere comes from plants, which extract it from soil
  • The availability of nitrogen in soil often limits growth of plants, limiting the amount of food we can produce
  • The amount of naturally occurring nitrogen in soil would enable us to grow enough food for about 4 billion people
• • In 1972, the U.S. Bureau of Chemistry and Soils calculated the chemicals within a human body to be worth less than a dollar
  • The tissues, organs, and biomolecules within a human being have an estimated value of $45,000,000
• • Carbon is extremely versatile in terms of the number and variety of chemical bonds that it can form
  • This enables creation of a wide array of complex molecules
• • Silicon is the "next-best" candidate as a chemical foundation for life
  • Carbon-to-carbon bonds are stronger than silicon-to-silicon bonds (more stable biomolecules)
  • More energy released on combustion of carbon-carbon bonds (more energy from carbon-based nutrients)
  • Combustion products of carbon (carbon dioxide) are soluble and remain active in biosphere (recycling)
• Common Functional Groups


  • Hydroxyl
  • Carbonyl
  • Carboxyl
  • Amino
  • Sulfhydryl
  • Phosphate

  
• • For all biomolecules, structure dictates function
  • Molecules do what they do because of their structures
  • Understanding the structure-function relationship of biomolecules allows one to predict molecular function, understand complex biology (and pathobiology), and rationale development of treatments
• Conformation


  Flexible spatial arrangement of atoms within a molecule (can be changed without breaking covalent bonds)
• Configuration


  Fixed spatial arrangement of atoms within a molecule (cannot be changed without breaking covalent bonds)
• Cis


  Groups on the same side of a double bond
• Trans


  Groups on opposite sides of a double bond
• Geometric (cis-trans) isomers can have very different biological properties

  
• Chiral carbon


  A carbon with four different substituents attached, which can be arranged in different ways in space yielding two stereoisomers
• While the chemical properties of stereoisomers tend to be identical, their biological properties are often distinct

  
• • Biomolecules are often constructed exclusively from one stereoisomer. For example, proteins are built entirely from L-Amino acids
  • Interactions between biomolecules, as well as between biomolecules and small molecules, are stereospecific

  
• • Synthesis of chemical compounds (such as drugs) which have an asymmetric carbons result in a mixture of all the chiral forms
  • These forms may have different biological activities
  • For example, thalidomide has two chiral forms, one of which causes birth defects

  
• • Biomolecules often polymers of simple building blocks
  • The structure and function of the resulting biomolecules are more complex than their precursor molecules; the whole is greater than the sum of the parts
  • Advantages of constructing biologicals as polymers: Simplicity, Recycling, Diversity
• Four Major Classes of Biomolecules

  • Proteins
  • Carbohydrates
  • Nucleic Acids
  • Lipids

  
• Proteins


  • Linear polymers of amino acids
  • There are 20 different amino acids
• Polysaccharides


  • Monosaccharides linked together to form linear or branched polymers
  • Serve many important biological roles including structural, energy storage, and cellular recognition

  
• Nucleic Acids


  • Linear polymers of nucleotide building blocks (5 building blocks for DNA and RNA)
  • Involved in all aspects storage and utilization of genetic information
• Lipids


  • Lipids are aggregates (rather than defined polymers) of building blocks
  • Lipids serve in energy storage, formation of membranes, and signalling
• Prokaryotes


  • Small (~ 1µm diameter), simple, single cell organisms (such as bacteria)
  • Rapid growth allow quick adaptation to changing environmental conditions
  • A single compartment, the nucleoid, which contains nucleic acid. Other biomolecules (proteins, metabolites, etc.) in a complex, organized mix
• Eukaryotes


  • Large (~100 µm diameter) complex cells
  • Make up multi-cellular organisms such as yeast, plants, fungi, vertebrates
  • Organelles (nucleus, mitochondria, golgi, endoplasmic reticulum, etc) to support specialized functions
• Nucleotide


  Building blocks of DNA and RNA
• Genetic information


  • Stored in a stable form
  • Expressed accurately in the form of gene products
  • Reproduced with minimal errors
• DNA


  • Provides the instructions for forming all other cellular components
  • Provides a template for production of identical DNA molecules to be distributed to the progeny when a cell divides
• The basic unit of DNA is two complementary strands
• Each DNA strand is a linear polymer of four different types of building blocks
• The linear sequence within the DNA strands encodes information
• The nucleotide sequence of genes


  Dictates the sequence of amino acids incorporated into the corresponding protein
• The amino acid sequence of the protein

  Dictates its structure
• The structure of the protein


  Dictates its biological activity
• Random changes in genotype (genetic information) can result in a change in phenotype (observable characteristics)
• If a change in genotype offers a survival advantage it will be selected for over time, if it disadvantages the organism it will be selected against