Biochemistry Objectives 2
1.
Oxygen effect of iron position in hemoglobin: oxygen binding pulls iron into
the plane of the heme
2.
Cooperative binding of oxygen improving oxygen transport: when oxygen
binds one hemoglobin subunit, it pulls the proximal histidine closer to the heme
and breaks salt bridges. These salt bridges then allow other subunits to bind
oxygen more effectively, thus making hemoglobin a cooperative molecule.
3.
Bohr effect and Hb structure: low pH causes His 146 to bind H+, attracting
Asp 94 and ultimately making a His 146-Asp 94 salt bridge. This salt bridge
changes R state hemoglobin to T state hemoglobin, and reduces Hb oxygen
binding affinity.
4.
CO2 effect and Hb structure: CO2 binds to the N-terminus of a subunit, and
forms a salt bridge between the newly formed carbamino group and an α-helix
changing R state hemoglobin to T state hemoglobin and reducing Hb oxygen
binding affinity.
5.
BPG and Hb structure: BPG is negatively charged and inserts itself into the
inner, positively charged cleft of T state hemoglobin. Thus, the T state is
stabilized, and HB oxygen binding affinity is reduced.
6.
CO and Hb structure: CO binds to reduced, ferrous iron irreversibly, and thus,
renders hemoglobin unable to bind oxygen
7.
Thalassemia: absence or reduced synthesis of one (or more) of the globin chains
Aberrant hemoglobins in thalassemias:
a.
α-thalassemias: mostly deletions (only one type of adult α hemoglobin);
one or two heterozygous deletions cause α-thalassemia minor, one
homozygous deletion causes α-thalassemia major (HbH), and both
homozygous deletions causes hydrops fetalis
 Note: HbH is β4 hemoglobin, and Hb Bart’s is γ4 hemoglobin
b.
8.
β-thalassemias: β chain can have deletion, intermediate function, or full
function, and can also be replaced by either γ or δ chains. One
heterozygous deletion or intermediate functioning β chain causes βthalassemia minor, two intermediate functioning to one intermediate and
one deletion causes β-thalassemia intermedia, and one intermediate and
one deletion to two deletions causes β-thalassemia major
Embryonic forms of hemoglobin:
a.
Hb Gower 1: ξ2ε2
b.
Hb Gower 2: α2ε2
c.
Hb Portland: ξ2γ2