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 • 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 • 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 • Two chains tied together by two “disulfide bridges”
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 • 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 • 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 • Insulin is stored in pancreas cells as “hexamers” (6-units) • Stabilized by a Zinc atom at center of the cluster
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.
Monosaccharides (glucose) added to the polysaccharide with some branching
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