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An Example of Macromolecules in Action. Insulin. Diabetes: Deadly disease. Before about 1922, anyone who developed diabetes would die within a year or two. They would literally starve to death, dropping into a coma at the end. Insulin: A New Hope.

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an example of macromolecules in action
An Example of

Macromolecules in Action

Insulin

diabetes deadly disease
Diabetes: Deadly disease
  • Before about 1922, anyone who developed diabetes would die within a year or two.
  • They would literally starve to death, dropping into a coma at the end.
insulin a new hope
Insulin: A New Hope
  • Frederick Banting, Charles Best and J.J.R. Macleod discovered that an extract made from a dog’s pancreas could keep alive dogs that had been made diabetic.
  • Banting and Best injected a 14-year old boy with crude insulin – He lived another 13 years (with daily injections)
  • Insulin therapy was born! And they were given the Nobel Prize for medicine.
discovery of insulin s primary structure
Discovery of Insulin’s Primary Structure
  • Fred Sanger in 1955 determined insulin’s sequence of amino acids
  • He was given the Nobel Prize—it was the first protein ever sequenced
  • But still have a puzzle to solve—2 peptide chains. How does it look in nature?
insulin s primary structure
Insulin’s Primary Structure
  • Two chains tied together by two “disulfide bridges”
discovery of insulin s secondary structure
Discovery of Insulin’s Secondary Structure
  • In 1969 Dorothy Hodgkin used X-ray crystallography to determine the 3-dimensional structure of insulin
  • Was given Nobel Prize earlier for vitamin B12 structure

X-Ray Diffraction pattern of insulin

secondary and tertiary structures of insulin
Secondary and Tertiary Structures of Insulin
  • http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2010/Holzwarth/structure.html
  • Secondary structure (shape of the peptide chain regions):
    • Alpha helix regions
    • Pleated sheets
  • Tertiary structure (shape of whole protein)
    • Disulfide bridges
    • Hydrogen bonds
quaternary structure of active insulin
Quaternary Structure of Active Insulin
  • Insulin is active as a “dimer” (2-units)
  • Held together by hydrogen bonding
  • http://www.3dchem.com/3dmolecule.asp?ID=196
quaternary structures of stored insulin
Quaternary Structures of Stored Insulin
  • Insulin is stored in pancreas cells as “hexamers” (6-units)
  • Stabilized by a Zinc atom at center of the cluster
what d oes insulin do
What Does Insulin Do?
  • High glucose in blood triggers its release from pancreas
  • Insulin is a “Messenger” type protein – it delivers a command to liver and muscle cells to:
    • Take up glucose from the blood and make more in glycogen (a polysaccharide) from these monosaccharides.
    • Take up fatty acids from the blood and make more fats (triglycerides) from them.
genetic engineering human insulin is now made in bacteria and yeast
Genetic Engineering: Human Insulin is now made in bacteria and yeast
  • Gene for human insulin was made and inserted into a microbial cell
  • As the microbes grow, insulin is produced
  • No more allergies to pig or cow insulin