BCHM 310 Lecture 24: BCHEM 315 9:1
22 Dec 2018
School
Department
Course
Professor
BCHEM 315 9/1
Hb
- Located in RBC
- 1/3 of mass of RBC corresponds to Hb
- O2 transport + CO2 transport
- 4 structure: Hb has but Mb does not
o 2 a globins and 2 B globins
o More complex O2 binding mechanism req for proper physio function- needs 4
subunits to come together
- Arterial blood is 96% saturated w O2
- Venous blood is 64% sat w O2
- Hb loses approx. 1/3 of its O2 cargo under normal conditions
O2 binding
Hb curve is sigmoidal- suggests cooperative binding mechanism so
need more than 1 binding site
- Allows for sensitivity for small changes in pO2
o High pO2 in lung
o Low pO2 in tissue
Hb tetramer
- 2 a and 2 B subunits linked via non-covalent interactions
- 1 a and 1 B form a rigid aB heterodimer
o 2 heterodimers form a tetramer
o The interface b/n two heterodimers is some what flexible or dynamic
Conformational state of Hb
1. Tense (T) state: no O2 present, numerous electrostatic interactions b/n 2 B subunits
2. Relaxed (R) state: O2 present, all sites were completely sat, fewer interactions at the B-B
interface (less electrostatics)
a. O2 binding induces conform change in Hb (change in affinity for O2)
b. O2 can bind to both T and R states BUT the R-state has a higher affinity for O2
c. Even when fully sat DN mean there is irrev binding, there is just enough O2 for
there to always be 4 O2 on Hb
Mechanism
1. Start at T state- some O2 binding and releasing
a. As pO2 incr the fractional saturation at each site incr
Document Summary
1/3 of mass of rbc corresponds to hb. 4 structure: hb has but mb does not: 2 a globins and 2 b globins, more complex o2 binding mechanism req for proper physio function- needs 4 subunits to come together. Arterial blood is 96% saturated w o2. Venous blood is 64% sat w o2. 1/3 of its o2 cargo under normal conditions. Hb curve is sigmoidal- suggests cooperative binding mechanism so need more than 1 binding site. Allows for sensitivity for small changes in po2: high po2 in lung, low po2 in tissue. 2 a and 2 b subunits linked via non-covalent interactions. 1 a and 1 b form a rigid ab heterodimer: 2 heterodimers form a tetramer, the interface b/n two heterodimers is some what flexible or dynamic. Allostery: binding of ligand to one site affects binding properties of other sites on the same molecule: hb: positive cooperativity/allostery, binding of one ligand enhances binding of subsequent ligands.
