Hemoglobin S

In HbS, the nonpolar amino acid valine has replaced the polar surface residue Glu6 of the P subunit, generating a hydrophobic "sticky patch" on the surface of the P subunit of both oxyHbS and deoxyHbS. Both HbA and HbS contain a complementary sticky patch on their surfaces that is exposed only in the deoxy-genated, R state. Thus, at low Po2, deoxyHbS can polymerize to form long, insoluble fibers. Binding of deoxy-HbA terminates fiber polymerization, since HbA lacks the second sticky patch necessary to bind another Hb molecule (Figure 6-11). These twisted helical fibers distort the erythrocyte into a characteristic sickle shape, rendering it vulnerable to lysis in the interstices of the splenic sinusoids. They also cause multiple secondary clinical effects. A low Po2 such as that at high altitudes exacerbates the tendency to polymerize.

Oxy A

Deoxy A

Oxy S

Deoxy S

Oxy A

p

a

a

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Deoxy A Deoxy S

Figure 6-11. Representation of the sticky patch (A) on hemoglobin S and its "receptor" (A) on deoxyhemoglobin A and deoxyhemoglobin S. The complementary surfaces allow deoxyhe-moglobin S to polymerize into a fibrous structure, but the presence of deoxyhemoglobin A will terminate the polymerization by failing to provide sticky patches. (Modified and reproduced, with permission, from Stryer L: Biochemistry, 4th ed. Freeman, 1995.)

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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