Hemoglobin A (HbA), the major hemoglobin in adults, is composed of four polypeptide chains (two α chains and two β chains, α2β2) held together by noncovalent interactions (Fig. 3.25). The subunits occupy different relative positions in deoxyhemoglobin compared with oxyhemoglobin. The deoxy form of Hb is called the “T,” or taut (tense), conformation. It has a constrained structure that limits the movement of the polypeptide chains. The T form is the low-oxygen-affinity form of Hb. The binding of oxygen (O2) to the heme iron causes rupture of some of the ionic and hydrogen bonds and movement of the dimers. This leads to a structure called the “R,” or relaxed, conformation. The R form is the high-oxygen-affinity form of Hb. The oxygen-dissociation curve for Hb is sigmoidal in shape (in contrast to that of myoglobin, which is hyperbolic), indicating that the subunits cooperate in binding O2. The binding of an oxygen molecule at one heme group increases the oxygen affinity of the remaining heme groups in the same Hb molecule (cooperativity). Hb’s ability to bind O2 reversibly is affected by the partial pressure of oxygen (pO2), the pH of the environment, the partial pressure of carbon dioxide (pCO2), and the availability of 2,3-bisphosphoglycerate (2,3-BPG). For example, the release of O2 from Hb is enhanced when the pH is lowered or the pCO2 is increased (the Bohr effect), such as in exercising muscle, and the oxygen-dissociation curve of Hb is shifted to the right. To cope long-term with the effects of chronic hypoxia or anemia, the concentration of 2,3-BPG in red blood cells increases. 2,3-BPG binds to the Hb and decreases its oxygen affinity. It therefore also shifts the oxygen-dissociation curve to the right. Fetal hemoglobin (HbF) binds 2,3-BPG less tightly than does HbA and has a higher oxygen affinity. Carbon monoxide (CO) binds tightly (but reversibly) to the Hb iron, forming carboxyhemoglobin. Hemoglobinopathies are disorders primarily caused either by production of a structurally abnormal Hb molecule as in sickle cell anemia or synthesis of insufficient quantities of normal Hb subunits as in the thalassemias (Fig. 3.26).
Choose the ONE best answer.
.1. Which one of the following statements concerning the hemoglobins is correct?
A. HbA is the most abundant hemoglobin in normal adults.
B. Fetal blood has a lower affinity for oxygen than does adult blood because HbF has an increased affinity for 2,3-bisphosphoglycerate.
C. The globin chain composition of HbF is α2δ2.
D. HbA1c differs from HbA by a single, genetically determined amino acid substitution.
E. HbA2 appears early in fetal life.
Correct answer = A. HbA accounts for over 90% of the hemoglobin in a normal adult. If HbA1c is included, the percentage rises to ~97%. Because 2,3bisphosphoglycerate (2,3-BPG) reduces the affinity of hemoglobin for oxygen, the weaker interaction between 2,3-BPG and HbF results in a higher oxygen affinity for HbF relative to HbA. HbF consists of α2γ2. HbA1c is a glycated form of HbA, formed nonenzymically in red blood cells. HbA2 is a minor component of normal adult hemoglobin, first appearing shortly before birth and rising to adult levels (~2% of the total hemoglobin) by age 6 months.