Hemoglobin Flashcards
Oxygen solubitility in H2O
Low
2 mechs for supplying oxygen to where it is needed
Circulatory system and system of oxygen transport and storage
Mb
Container
Resident in msucles
Stores til needed
Not allosteric
Hb
Carrier
Found in RBCs…transports O2, H+, and CO2
Allosteric
Hands O2 off to myoglobin
Myoglobin structure
Mostly alpha helical with a heme…binds 1 oxygen
Hemoglobin basic structure
2 alpha and 2 beta chains
A2B2 heterotetramer
Each chain binds a heme and is similar to myoglobin
Oxygen binding ability due to
Cofactor (prosthetic group) known as a heme
Heme location
Sandwiched in a cleft with a histidine on each side
Oxygen binding to heme
Iron coordinated by proximal histidine (F8)
Oxygen binding site between iron and distal histidine (E7)
Iron is out of heme plane towards proximal when not bound and move in plane towards distal when oxygen bound
Isolated heme binding and what happens in H2O
Isolated heme binds weakly
O2 oxidizes Fe(2) into Fe(3)
Oxidized heme
Cannot bind oxygen
Heme bound by myoglobin and hemoglobin
Cannot associate with other heme groups
Protein increases heme affinity for O2 and prevents heme from being oxidized
Hb binding
Cooperatively (allosteric)
Effector or modulator
Allosteric ligand
Allostery normally results from
INteractions between subunits in oligomeric proteins
Homo vs. heterotropic interactions
Ligands are identical/differ
Oxygen type of ligan
Positive homotropic allosteric effector
IN metabolically active muscle
Higher Co2 and H+ lead to release of O2
CO2, H+, and BPG Act as negative heterotropic allosteric effectors…BPG also high
In alveolar capillaries
Higher pH (low H+) and higher O2 concentration promotes unloading of Co2 and H+ and binding of O2...BPG also low O2 is positive, homotropic allosteric effector
BPG
Only binds deoxygenated Hb
Needed in order for Hb to release O2
Negative heterotropic allosteric effector
Isolated alpha and beta chains
A - like myoglobin…high O2 affinity and not allosteric
B - forms B4 tetramer that is like MB…higher O2 affinity and not allosteric
Allosteric properties of Hb from
Interactions between subunits of A2B2 tetramer
Quaternary changes upon O2 bidning
alpha(1) and B(2) interface changes as well as vce verse
A(1)B(1) moves about 15 degrees
Oxygenated in relaxed while deoxygenated tense
Oxygen binding effect on heme
Pulls on proximal histidine that is part of an alpha helix…causes change to the R state
Stabilizes R state relative to T state
Mech of negative allosteric effectors
Stabilize the T state
BPG binds in central cavity between the four subunits
Fetal hemoglobin
Higher affinity for oxygen because BPG binds less strongly
Isoform (Hb F vs. Hb A)
Deoxy Hb F can take O2 from Oxy Hb A
