The Chemistry of Insulin

Frederick Sanger, Nobel Prize 1958

Presented by Jung Kim

Sanger Developed complete amino acid sequence of insulin.

Proved that proteins have specific structures.

Structure of Insulin

His Experiment
Degraded insulin into short fragments

A solvent

Electric Current

Trypsin

Insulin solution

Results
Depending on the solubility and charge, insulin fragments moved to different positions on the paper creating a pattern.

Sanger called these patterns fingerprints.

Interpretation
Like human fingerprints, these fragments were characteristic for each protein (simple and reproducible).
He was able to name each protein. He then reassembled the fragments into longer sequences to name the protein 1st Nobel Prize in sequences in insulin.
Chemistry in 1958.

Amino Acid
Any molecule that contains both amine and carboxyl functional groups
H Amine Group N H C R C OH O Carboxyl Group

Also called alpha amino acids b/c both are attached to the same carbon, the -carbon. (Amino acid = shorthand).

Proteins
Amino acids are the basic components of proteins. 20 standard amino acids in organisms.
H N H H C R Peptide bond forms Forms long

H2O

C OH H

H O

N
H of

C
R

C
OH amino acids

sequence

Protein Sequence & Shape

Proteins have its own unique sequence = Primary Structure Like letters of an alphabet amino acids are combined to form various protein sequences. The unique shape in the protein causes each to be specialized for a function.
Called Secondary and Tertiary Structures.

Primary Structure
Equivalent to specifying the sequence of the nucleoptide or peptide sequence.
Unbranched polymers Specified by the sequence of amino acids

Secondary Structure
Loops and grooves within the shape of protein.
Most common:
Alpha helices Beta sheets

Tertiary Structure
3-D folding of protein sequences. The overall shape, also called fold. Determinants of protein structure.
One Kind

Globular proteins: Hydrophobic amino acids in protein core where H2O has been excluded & charged, hydrophilic residues on proteins waterexposed surface.

More is known about globular proteins than others because it is the easiest to study.

Experimental Determination
X-ray Crystallography (most common)
Data on high resolution, no time dependent info on proteins flexibility.

Protein NMR (Nuclear Magnetic Resonance spectroscopy)

Lower resolution data, limited to small proteins, time dependent info about motion of protein in solution.

Insulin
Latin: insula island. Produced in the Islets of Langerhands in the pancreas. Regulates carbohydrate metabolism in the body. 7% of the population has diabetes, due to defects in insulin production. Diabetes leads to premature death and extensive number of complications. However control of insulin helps regulate symptoms of disease.

Effects of Diabetes
Diabetes is the 6th most common cause of death in the U.S. The risk of death is twice as high for people with diabetes than people without diabetes. Health concerns: Heart disease, stroke, high blood pressure, blindness, kidney disease, nervous system disease, amputations, etc.

From the National Diabetes Information Clearinghouse (NDIC)

Treating Diabetes
To survive, people with type 1 diabetes must have insulin delivered by injections or a pump. Many people with type 2 diabetes can control their blood glucose by following a healthy meal plan and exercise program, losing excess weight, and taking oral medication. Many people with diabetes also need to take medications to control their cholesterol and blood pressure. Diabetes self-management education (DMSE) is an integral component of medical care. Among adults with diagnosed diabetes, 16 percent take insulin only, 12 percent take both insulin and oral medication, 57 percent take oral medication only, and 15 percent do not take either insulin or oral medications.