Figure 14-3 KINETICS OF HEMOGLOBIN S POLYMERIZATION, STUDIED BY NEAR-INSTANTANEOUS AND COMPLETE DEOXYGENATION.

A, Extreme dependence of delay time on hemoglobin concentration. B to D, Kinetic progress curves for polymer formation show that long delay times are highly variable (B), but very short delay times are highly reproducible (D). To the right is a representation of domains and corresponding red blood cell morphology postulated to result from these different scales of polymerization rate (see Fig. 14-1, B to E). E, Delay times for individual red blood cells are influenced by substituent hemoglobins. F, A double nucleation process is hypothesized to underlie polymer formation. G, Physiologically, the finite rate of deoxygenation effectively caps the polymerization rate and eliminates the relevance of delay times that are short relative to deoxygenation rate (<1 sec).

(A to E, Data from Eaton WA, Hofrichter J: Hemoglobin S gelation and sickle cell disease. Blood 70:1245, 1987; F adapted from Ferrone FA, Hofrichter J, Eaton WA: Kinetics of sickle hemoglobin polymerization II. A double nucleation mechanism. J Mol Biol 183:611, 1985; G, Data from Ferrone FA: Oxygen transits and transports. In Embury S, Hebbel RP, Mohandas N, Steinberg MH, eds: Sickle cell disease: basic principles and clinical practice, New York, 1994, Raven Press.)