Sickle

A typical electrospray analysis can be completed in 15 min with as little as 1 pmol of protein. An analysis of the cord blood of a baby (Figure 40.6) showed quite clearly that five globins were present, viz., the normal ones (a, (3, Gy, and Ay) and a sickle-cell variant (sickle (3). The last one is easily revealed in the mass spectrum, even at a level of only 4% in the blood analyzed. 

Electrospray mass spectra of globins from the blood of (a) a child diagnosed as having the sickle-cell anemia trait and (b) of its mother. As well as the usual p-globin sickle-cell variant at m/z 15,837.2, a new variant (P-Montreal-Chori) appears at m/z 15,879.3 and is observed in both the child and the mother. 

The plant is harvested by hand sickle and, after defoUation, is stripped and scraped by hand or machine decorticated. Because of the high gum (xylan and araban) content of up to 35%, retting is not possible. The fibers are separated chemically by boiling in an alkaline solution in open vats or under pressure, then washed, bleached with hypochlorite, neutralized, oiled to facUitate spinning, and dried. 

Coconut. In 1988, total coconut production was 36,802,000 t, of which 81% was produced in Asia, mainly in Indonesia and the Philippines (157). The coconut is essentiaUy a crop of the lowland tropics (157). On the average, five nuts are required to produce 1 kg of copra, the dried endosperm of the nut. Copra is further processed to obtain coconut oil and copra meal. To produce coconut milk, which is an emulsion of coconut oil and water, grated fresh coconut meat is mixed with hot water and pressed (157). Either poles having an attached sickle-shaped knife or monkeys (158) may be used for harvesting. 

Sheldon, L., Zelon, H., Sickles, J., Eaton, C., and Hartwell, T. (1988) "Indoor Air Quality in Public Buildings," Vol II. Environmental Monitoring Systems Laboratory, Office of Research and Development, U.5. Environmental Protection Agency. 

Lesk and Chothia did find, however, that there is a striking preferential conservation of the hydrophobic character of the amino acids at the 59 buried positions, but that no such conservation occurs at positions exposed on the surface of the molecule. With a few exceptions on the surface, hydrophobic residues have replaced hydrophilic ones and vice versa. However, the case of sickle-cell hemoglobin, which is described below, shows that a charge balance must be preserved to avoid hydrophobic patches on the surface. In summary, the evolutionary divergence of these nine globins has been constrained primarily by an almost absolute conservation of the hydro-phobicity of the residues buried in the helix-to-helix and helix-to-heme contacts. 

Sickle-cell hemoglobin confers resistance to malaria... 

Sickle-cell anemia is the classic example of an inherited disease that is caused by a change in a protein s amino acid sequence. Linus Pauling proposed in 1949 that it was caused by a defect in the hemoglobin molecule he thus coined the term molecular disease. Seven years later Vernon Ingram showed that the disease was caused by a single mutation, a change in residue 6 of the P chain of hemoglobin from Glu to Val. 

Figure 3.14 Sickle-cell hemoglobin molecules polymerize due to the hydrophobic patch introduced by the mutation Glu 6 to Val in the P chain. The diagram (a) illustrates how this hydrophobic patch (green interacts with a hydrophobic pocket (red) in a second hemoglobin molecule, whose hydrophobic patch interacts with the pocket in a third molecule, and so on. Electron micrographs of sickle-cell hemoglobin fibers are shown in cross-section in (b) and along the fibers in (c). [(b) and (c) from J.T. Finch et al., Proc. Natl. Acad. Set. USA 70 718-722, 1973.)...

Embury, S.H. The clinical pathophysiology of sickle-cell disease. Annu. Rev. Med. 37 361-376, 1986. 

Finch, J.T., et al. Stmcture of sickled erythrocytes and of sickle-cell hemoglobin fibers. Proc. Natl. Acad. Sci. USA 70 718-722, 1973. 

Ingram, V.M. Gene mutation in human haemoglobin the chemical difference between normal and sickle cell haemoglobin. Nature 180 326-328, 1957. 

In certain reglon.s of Africa, tire. sickle-cell trait Is found In 20% of the people. Wiry does snch a deleterious heritable condition persist in dre popnladon For reasons as yet unknown, individnals widr this trait are less sn.scepdble to dre most virnlent form of malaria. The geographic distribn-don of malaria and dre sickle-cell trait are posidvely correlated. 

Slchcl,/. sickle cresceat.. filchelformig, a. crescent-shaped, filcher, a. safe, secure, certain, sure, reliable. — — fitellen, make safe, secure, ensure, guarantee. 

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