Lecture 15 - Myoglobin and Hemoglobin

Question 1

Myoglobin

Answer 1

• Stores oxygen
• rich in helices
• affinity of myoglobin for O2 is such that O2 is readily released in oxygen-deprived muscle tissue when pO2 is 5-10 mm Hg

Question 2

Hemoglobin

Answer 2

• transports O2, CO2, and protons
• deoxyhemoglobin is termed the T (tense or taut) form and oxyhemoglobin the R (relaxed) form
• In the T state, non-covalent forces between the heterodimers are stronger
• Deoxyhemoglobin (T form) is constrained by salt links between different chains
• O2 binding at one subunit allows additional O2 molecules to bind with less steric hindrance - O2 binds to the empty hemes with greater affinity

Question 3

Myoglobin v. Hemoglobin

Answer 3

• myoglobin and B subunits of hemoglobin have nearly identical secondary and tertiary structures
• Major difference between the two is that myoglobin is monomeric and many of the surface proteins interact with water and are polar, whereas hemoglobin subunits have many surface residues that interact with other subunits via hydrophobic bonds and H bonds
• Proximal and distal histidines and amino acids in heme pocket are preserved

Question 4

2,3 bisphoshoglycerate (BPG)

Answer 4

• lowers the O2 affinity of hemoglobin
• Binding of BPG to Hb stabilizes the T conformation and increases its concentration relative to the R form
• BPG dissociates as deoxy-Hb binds oxygen
• Conditions that cause hypoxia (deficiency of oxygen) such as anemia, smoking and high-altitude, increase BPG levels in the red blood cells
• Fetal hemoglobin has lower affinity for 2,3 bisphosphoglycerate which gives it the higher O2 affinity
• Reduced affinity of HbF for BPG is due to change in sequence (His143 in HbA is Ser 143 in HbF)

Question 5

Carbon Monoxide Poisoning

Answer 5

• Loss of one half of one’s hemoglobin to CO-Hb can be fatal
• This is because as CO binds to one or two subunits, the affinity for O2 in the remaining subunits increases dramatically
• Thus a Hb tetramer with two bound CO molecules can efficiently bind O2 in the lungs but releases very little in the tissues
• Symptoms range from headache at 0.0035% to death at 1.3%
• Affects mainly hemoglobin, myoglobin, and cytochrome oxidase
• Treatment involves removal from source, administration of 100% oxygen through a non rebreather mask (to prevent inhalation of exhaled gas), and if needed hyperbaric oxygen therapy, where 100% oxygen is provided at 2-3 times normal pressure