Chemistry 474/674

Learning Objectives – Chapter 3

• Reading:
o Read all sections in this chapter (except 3.4).
o Pay less attention to the subsection about carbon monoxide in section 3.2.
• What are the structural characteristics of hemoglobin (Hb)?
o What type of secondary structure is prevalent in Hb? How many subunits does it have?
How do the subunits compare with each other?
• What is meant by “cooperativity of binding”?
• What is an “allosteric” protein?
• How is the structure of myoglobin (Mb) different from that of hemoglobin?
• What is the prosthetic group in both myoglobin and hemoglobin? (And what’s a prosthetic
group, anyway?)
o What is the structure of this prosthetic group? (You don’t need to memorize the
structure. I won’t ask you to reproduce it on an exam, but you do need to know the
major component parts of the structure.)
o Where is the prosthetic group located in the protein?
o What are the differences between the iron(III) and iron(II) ions? How do these
differences affect the functions of myoglobin and hemoglobin?
o How does the prosthetic group interact with the myoglobin and hemoglobin proteins?
• What structural changes occur when oxygen binds to the heme group in either myoglobin or
hemoglobin? How do these structural changes result in cooperativity of binding in
hemoglobin?
• What is the superoxide ion? How is it formed in myoglobin and hemoglobin? How is it
stabilized?
• What is an oxygen binding curve? How does the oxygen binding curve of myoglobin differ
from that of hemoglobin?
o What is the shape of the Mb oxygen binding curve?
o What is the shape of the Hb oxygen binding curve? What does the shape of the Hb
oxygen binding curve indicate about the binding of oxygen to Hb?
o How do the shapes of the Mb and Hb oxygen binding curves indicate that Hb is a
more efficient oxygen transport protein than Mb?
o What is a P50 value? What information does it give you?
o Let’s say that you have a graph on which two different oxygen binding curves are
plotted. What can you say about the oxygen affinity of the molecule whose curve is
furthest to the left on the graph? What can you say about the oxygen affinity of the
molecule whose curve is furthest to the right on the graph?
• What are the differences between the T and R states of hemoglobin?
o Which state is predominant in the absence of oxygen?
o Which state is predominant in the presence of oxygen?
o Which state binds oxygen more tightly? Which state binds oxygen more loosely? How
is the length of the Fe-N(porphyrin) bond in the heme prosthetic groups related to
the strength of oxygen binding in Hb?
o Which state is most useful for picking up oxygen in an oxygen-rich atmosphere?
Which state is most useful for releasing oxygen in an oxygen-poor atmosphere?
 o What structural changes occur in the Hb molecule during the T à R transition?
• How are the structural changes that occur on oxygen binding at one heme group
communicated to heme groups on other subunits? (You should know the details of how this
happens. See slide 22.)
o How does the binding of oxygen at one subunit affect the oxygen binding affinity at
other subunits in the same Hb molecule?
• What is an allosteric effector?
o What is the difference between a positive allosteric effector and an allosteric inhibitor?
o What is the difference between a homotropic effector and a heterotropic effector?
o Why are allosteric inhibitors needed to regulate Hb?
o How do the following inhibitors affect Hb’s affinity for oxygen: 2,3-BPG, protons,
carbon dioxide? (You need to know HOW and WHY these allosteric effectors
influence Hb’s affinity for oxygen. For example, it is not acceptable to simply know
that 2,3-BPG lowers Hb’s affinity for oxygen. You should know WHY 2,3-BPG
lowers Hb’s affinity for oxygen.)
§ Where and why are these allosteric effectors (2,3-BPG, protons, and carbon
dioxide) produced? How does their production (and the location of their
production) allow Hb to deliver oxygen where it is most needed? (You should
also consider the answer to this last question in relation to altitude adjustment,
breathing by smokers, and the oxygen needs of a developing fetus.)
• What is the Bohr effect?
• How do the physiological conditions in the tissues and the lungs affect whether Hb loads or
unloads oxygen? (See slide 40.)
• Why/how does sickle-cell anemia result in a deficiency of red blood cells? What structural
changes result in cells containing sickle-cell Hb (HbS) being less functional?
o The only difference between normal adult Hb and sickle-cell Hb is one amino acid
(Glu6 à Val6). This change decreases the solubility of deoxyhemoglobin, but it does
not affect the properties of oxyhemoglobin. Why is this?
o Why do people with sickle-cell trait only experience symptoms under conditions of
severe hypoxia?

Recommended Practice Problems – Chapter 3

• Problems (p. 97-8): 8, 9, 10.