Hemoglobin and Myoglobin

Question 1

Myoglobin

Answer 1

Myoglobin is a monomer. It presents a compact, globular structure with 75% alpha-helices (8 alpha-helices, named from A to H).
o The interior contains predominantly nonpolar amino acids, and it is stabilized by hydrophobic interactions.The exterior is composed of charged amino acids which interact with water.
o Myoglobin does not have quaternary structure. The tertiary structure results in the globin fold domain, which creates a crevice between helices E & F for heme binding. Heme lies in this crevice lined with mostly nonpolar amino acids. Mb will bind 1(O2)/molecule.

Question 2

Hemoglobin

Answer 2

Hemoglobin is a tetramer. HbA is composed of two alpha-globin and two beta-globin polypeptide chains. Thus, HbA is a tetramer of two identical alpha/beta dimers. The alpha/beta dimers are stabilized through mainly nonpolar and
some polar interactions between the alpha and beta chains.
o The tetramer is stabilized through ionic bonds and hydrogen bonds between the two alpha/beta dimers. Different forms of Hb vary in globin chains.

Question 3

Fetal Hemoglobin

Answer 3

Fetal hemoglobin (HbF) has a higher affinity
for O2 than adult hemoglobin (HbA), to ensure
that the fetus obtains enough O2 during gestation.

Question 4

methemoglobin

Answer 4

Hb with ferric iron (Fe3+). Not active in binding O2

Question 5

The Hb/Mb Heme

Answer 5

The heme group is the physical location where O2 is bound to Hb and Mb. The heme group is a prosthetic group consisting of a protoporphyrin IX ring with a ferrous iron (Fe2+) in the center with 6 coordination sites: 4 sites are filled by the N of the planar porphyrin ring. In free heme, the other two sites are bound to water.
When the heme group is not free but is part of Hb or Mb: The 5th coordination site on one side of the porphyrin ring binds to the proximal histidine located in one of the a-helix of the protein (F-helix).
o The 6th coordination site on the other side of the porphyrin ring binds to an O2 molecule. The O2 is in turn stabilized by a distal histidine residue within the E-helix of the surrounding protein.

Question 6

prosthetic group

Answer 6

a small molecule tightly attached to a protein and essential for its function (ie heme)

Question 7

Myoglobin’s O2 dissociation curve

Answer 7

Myoglobin’s O2 dissociation curve is hyperbolic. Mb binds O2 tightly, a property that is well suited for storage.
o In the lungs (pO2~110), about 95% of Mb has O2 bound, i.e. 95% of the molecules are saturated.
o In the tissues (pO2~30), about 90% of Mb has O2 bound, i.e., 90% of the molecules saturated.
o Mb only releases significant amounts of O2 when the tissue is under stress conditions (pO2~10), i.e. working or anoxic muscle.

Question 8

Hemoglobin’s O2 dissociation curve

Answer 8

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