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"Abnormal Hemoglobin Molecules in Relation to Disease"
"Abnormal Hemoglobin Molecules in Relation to Disease" April 21, 1972.
Lecture delivered at Michigan State University.

Ingram's Work on Sickle Cell Hemoglobin. (2:31)

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Linus Pauling: There was a man in England, now at MIT, named Ingram, who determined the detailed nature of the abnormality in the polypeptide chains by a method that he invented: paper, two-dimensional electrophoresis and chromatography of peptides. He attacked the polypeptide chains with trypsin, a proteolytic enzyme which splits each of them into thirteen short pieces of chain, about deca-peptides, perhaps. And a drop of that stuff was put on the paper, and the electric field causes it to move from the right to left and solvent flows and you get a chromatographic separation vertically.

Next slide. There’s only one spot that has shifted when you go from normal hemoglobin to sickle cell hemoglobin. It’s in that vertical line, not quite at the right edge, and has moved over from the line a little to the left in the right-hand picture. That turns out to be the first peptide in the beta chain, and analysis of the peptide shows that - next slide please - this shows what we see here.

The alpha chain starts valine, leucine, serine, and goes on. The beta chain valine, histidine, leucine, threonine, proline, glutamate. And the sickle cell beta is valine, histidine, leucine, threonine, proline, and then valine in the sixth position. The other 140 positions are occupied by the same amino acid. This involves just one nucleotide in the gene replaced in such a way that instead of glutamic acid, valine is introduced. Glutamic acid is really glutamate - the carboxylic group is ionized COO-. Valine has a hydrocarbon side chain, so you’ve lost one negative charge. There are two beta chains in the molecule. That means you’ve lost two negative charges in going to sickle cell hemoglobin.


Creator: Linus Pauling
Associated: Vernon M. Ingram
Clip ID: 1972v.3-ingram

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Creator: Linus Pauling
Associated: Michigan State University

Date: April 21, 1972
Genre: sound
ID: 1972v.3
Copyright: More Information

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