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The Chemistry of Insulin

Frederick Sanger, Nobel Prize 1958

Presented

by Jung Kim
http://en.wikipedia.org/wiki/Image:InsulinMonomer.jpg


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Sanger -

Developed complete amino acidsequence of insulin.

Proved that proteins have specificstructures.

Structure ofInsulin
http://en.wikipedia.org/wiki/Image:InsulinHexamer.jpg


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His Experiment

Degraded insulin into short fragments

Electric CurrentAsolvent

Insulin solutionTrypsin


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Results

Depending on the solubility andcharge, insulin fragments moved todifferent positions on the paper creating a pattern.

Sanger calledthese patternsfingerprints.


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Interpretation

Like human fingerprints, thesefragments were characteristic foreach protein (simple andreproducible).

He was able to name each protein.

He then reassembled the fragments intolonger sequences to name the proteinsequences in insulin. 1st Nobel Prize inChemistry in 1958.


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Amino Acid

Any molecule that contains both amine andcarboxyl functional groups

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

N C C

OH

O

R

HH

H

AmineGroup

CarboxylGroup


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Proteins

Amino acids are the basiccomponents of proteins.

20 standard amino acids inorganisms.

N

N

C

C

C

C

H2O

O

O

OH

OH

H

H

H

HH

HR

R

Peptidebond forms

F o r m s l o n g s e q u e n c e o f a m i n o a c i d s


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Protein Sequence & Shape

Proteins have its own unique sequence =Primary Structure

Like letters of an alphabet amino acids

are combined to form various proteinsequences.

The unique shape in the protein causeseach to be specialized for a function.

Called Secondary and Tertiary Structures.


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Primary Structure

Equivalent to specifying the sequenceof the nucleoptide or peptidesequence.

Unbranched polymers

Specified by the sequence of amino acids
http://en.wikipedia.org/wiki/Image:Protein-primary-structure.png


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Secondary Structure

Loops andgrooves withinthe shape ofprotein.

Most common:

Alpha helices

Beta sheets
http://en.wikipedia.org/wiki/Image:Beta-parallel.pnghttp://en.wikipedia.org/wiki/Image:Myoglobin.pnghttp://en.wikipedia.org/wiki/Image:BetaPleatedSheetProtein.pnghttp://en.wikipedia.org/wiki/Image:AlphaHelixProtein.jpg


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Tertiary Structure

3-D folding of protein

sequences.

The overall shape,

also called fold. Determinants of protein structure.

Globular proteins: Hydrophobic amino acids inprotein core where H2O has been excluded &

charged, hydrophilic residues on proteins water-exposed surface.

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

One

Kind
http://en.wikipedia.org/wiki/Image:InsulinMonomer.jpg


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Experimental Determination

X-ray Crystallography

(most common)

Data on high resolution,

no time dependent info

on proteins flexibility.

Protein NMR(Nuclear Magnetic Resonancespectroscopy)

Lower resolution data, limited to small proteins,time dependent info about motion of protein insolution.
http://en.wikipedia.org/wiki/Image:Insulincrystals.jpg


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Insulin

Latin: insulaisland. Produced in theIslets 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 regulatesymptoms of disease.


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Effects of Diabetes

Diabetes is the 6th most commoncause of death in the U.S.

The risk of death is twice as high for

people with diabetes than peoplewithout diabetes.

Health concerns: Heart disease,

stroke, high blood pressure,blindness, kidney disease, nervoussystem disease, amputations, etc.


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From the National DiabetesInformation Clearinghouse (NDIC)

Treating Diabetes

To survive, people with type 1 diabetes must have insulin delivered byinjections or a pump.

Many people with type 2 diabetes can control their blood glucose by following ahealthy meal plan and exercise program, losing excess weight, and takingoral medication.

Many people with diabetes also need to take medications to control theircholesterol and blood pressure.

Diabetes self-management education (DMSE) is an integral component ofmedical care.

Among adults with diagnosed diabetes, 16 percent take insulin only, 12percent take both insulin and oral medication, 57 percent take oralmedication only, and 15 percent do not take either insulin or oralmedications.


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