1. In every red blood
cell there are 280 million molecules of hemoglobin, a critical
protein. Read a few pages introducing hemoglobin.
http://www.concord.org/~barbara/homs_workbench/blood2.html
2.
Hemoglobin protein is a long twisted strand of amino acids, altogether
carefully cradling a heme, a disk whose iron in the center attracts,
carries and releases oxygen.
Image: Dickerson p. 16
3.One
hemoglobin is made of 4 protein protein chains, or globins, Two
strands are "alpha" chains, and two are "beta"
strands. The 4 strands assemble together so that, like a ball
glove, it can carry oxygen. When assembled, a normal hemoglobin
has indentations in the strands. It is completely surrounded
by water molecules.
Image: Dickerson p.17
4.
In sickle cell valine is substituted for glutamic acid in both
beta chains. This changes the shape of the protein: a small protrusion
(or dent?) appears on the surface of the proteins.
Image: http://rad.usuhs.mil/sickle/index.
5.
This bump fits exactly into the existing "pocket" on
the surface of the next protein. The two proteins "clump"
together, then the third clumps...This creates a kind of domino
effect, leading to the formation of long fibers made of many
millions of damaged hemoglobin molecules. (polymerization) This
seems to happen when the hemoglobin does not have its oxygen.
The hemoglobin loses its solubility and clumps into bundles.
(Scientists are working on making the hemoglobin of Sickle Cell
patients more soluble.
Image: http://rad.usuhs.mil/sickle/index.
6. The long bundled
hemoglobins twist in a regular fashion.
7. These bundles self associate into even larger structures that
stretch and distort the cell into a sickle shape.
8.
The long fibers distend the cell.
9.
The sickled cells clog the capillaries, thereby delivering less
oxygen and causing pain.