Oxygenation of Hemoglobin Is Accompanied by Large Conformational Changes

The binding of the first O2 molecule to deoxyHb shifts the heme iron towards the plane of the heme ring from a position about 0.6 nm beyond it (Figure 6-6). This motion is transmitted to the proximal (F8) histidine and to the residues attached thereto, which in turn causes the rupture of salt bridges between the carboxyl terminal residues of all four subunits. As a consequence, one pair of a/p subunits rotates 15 degrees with respect to the other, compacting the tetramer (Figure 6-7). Profound changes in secondary, tertiary, and quaternary structure accompany the high-affinity O2-induced transition of hemoglobin from the low-affinity T (taut) state to the R (relaxed) state. These changes significantly increase the affinity of the remaining unoxy-genated hemes for O2, as subsequent binding events require the rupture of fewer salt bridges (Figure 6-8). The terms T and R also are used to refer to the low-affinity and high-affinity conformations of allosteric enzymes, respectively.

Histidine F8

Steric T repulsion

. Porphyrin 1 plane

F helix

HC CH N

Figure 6-6. The iron atom moves into the plane of the heme on oxygenation. Histidine F8 and its associated residues are pulled along with the iron atom. (Slightly modified and reproduced, with permission, from Stryer L: Biochemistry, 4th ed. Freeman, 1995.)

/ f y chain l / (fetal) \

\ / \ /

J

\ /p chain (adult) Y

1 c and Z chains \ (embryonic)

A / \ / \ / \ / \

\ /

\

Gestation (months) Age (months)

Gestation (months) Age (months)

Figure 6-5. Developmental pattern of the quaternary structure of fetal and newborn hemoglobins. (Reproduced, with permission, from Ganong WF: Review of Medical Physiology, 20th ed. McGraw-Hill, 2001.)

T form

Figure 6-7. During transition of the T form to the R form of hemoglobin, one pair of subunits (a2/p2) rotates through 15 degrees relative to the other pair (a1/p1). The axis of rotation is eccentric, and the a2/p2 pair also shifts toward the axis somewhat. In the diagram, the unshaded a1/p1 pair is shown fixed while the colored a2/p2 pair both shifts and rotates.

1 /

/axis\

/

/

/

y

ßl

115°

T form

R form

Figure 6-7. During transition of the T form to the R form of hemoglobin, one pair of subunits (a2/p2) rotates through 15 degrees relative to the other pair (a1/p1). The axis of rotation is eccentric, and the a2/p2 pair also shifts toward the axis somewhat. In the diagram, the unshaded a1/p1 pair is shown fixed while the colored a2/p2 pair both shifts and rotates.

T structure

T structure

R structure

Figure 6-8. Transition from the T structure to the R structure. In this model, salt bridges (thin lines) linking the subunits in the T structure break progressively as oxygen is added, and even those salt bridges that have not yet ruptured are progressively weakened (wavy lines). The transition from T to R does not take place after a fixed number of oxygen molecules have been bound but becomes more probable as each successive oxygen binds. The transition between the two structures is influenced by protons, carbon dioxide, chloride, and BPG; the higher their concentration, the more oxygen must be bound to trigger the transition. Fully oxygenated molecules in the T structure and fully deoxygenated molecules in the R structure are not shown because they are unstable. (Modified and redrawn, with permission, from Perutz MF: Hemoglobin structure and respiratory transport. Sci Am [Dec] 1978;239:92.)

R structure

Figure 6-8. Transition from the T structure to the R structure. In this model, salt bridges (thin lines) linking the subunits in the T structure break progressively as oxygen is added, and even those salt bridges that have not yet ruptured are progressively weakened (wavy lines). The transition from T to R does not take place after a fixed number of oxygen molecules have been bound but becomes more probable as each successive oxygen binds. The transition between the two structures is influenced by protons, carbon dioxide, chloride, and BPG; the higher their concentration, the more oxygen must be bound to trigger the transition. Fully oxygenated molecules in the T structure and fully deoxygenated molecules in the R structure are not shown because they are unstable. (Modified and redrawn, with permission, from Perutz MF: Hemoglobin structure and respiratory transport. Sci Am [Dec] 1978;239:92.)

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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