Hemoglobin Flashcards
1
Q
describe the 6 coordination bonds that the ferrous ion forms
A
ferrous ion = Fe2+ (ferric = Fe3+)
- 4 bonds form to the N atoms in the porphyrin ring
- 1 bond links to the globin protein
- 1 bond is free to reversibly bind O2
- iron ion is buried deep inside the globin protein
- helps to ensure that oxygen is released as O2
- O2 entrance and exit is in a defined path
2
Q
describe methemoglobin (MetHb)
A
- MetHb contains Fe3+ in the porphyrin ring
- Fe2+ gets oxidized to Fe3+
- occurs when superoxide is released instead of O2
- Ferric ion does bind to O2 when in heme
- the remaining 3 O2 sites do not release the O2 that is bound
- therefore, MetHb does not function as an O2 carrier
- Fe2+ gets oxidized to Fe3+
3
Q
contrast the O2 dissociation curve between myoglobin and hemoglobin
A
- myoglobin: hyperbolic, has a higher affinity for O2 than Hb
- storage of O2 in muscles for mt
- hemoglobin: sigmoidal, cooperative ligand binding
- transport of O2
4
Q
describe how O2 binding to heme leads to a conformational change in Hb
A
- normally the Fe ion is slightly out of plane of the heme ring
- the Fe atom moves into the plane of the heme when it is oxygenated
- proximal histidine and its associated residues are pulled along with the iron ion (tugging)
- this conformational change is transmitted to the other globin monomers in Hb
- explains cooperative O2 binding
- this conformational change is transmitted to the other globin monomers in Hb
5
Q
describe 2-3 BPG
A
- promotes formation of the taut state; decreases O2 affinity for Hb
- 2,3-BPG is negatively charged
- 2,3-BPG allows the formation of additional salt bridges between the aB/aB dimers
- this creates a driving force for Hb to assume the deoxyHb structure (taut form)
- promotes unloading O2 in the tissues
6
Q
what affect does 2,3-BPG have on Hb?
A
- higher levels of 2,3-BPG promote O2 release to the tissues
- decreases the affinity of Hb for O2
- 2,3-BPG is a negative allosteric effector
7
Q
contrast hexokinase deficiency vs pyruvate kinase deficiency
A
- hexokinase deficiency
- reduced 2,3 BPG levels
- left shift of binding curve
- increased O2 affinity
- pyruvate kinase deficiency
- elevated 2,3-BPG levels
- right shift on binding curve
- decreased O2 affinity
8
Q
describe the Bohr effect
A
- as pH decreases, Hb O2 affinity decreases
- aerobic/active tissues form CO2 –> HCO3-
- CO2 and H+ ions signal need for more O2
- aerobic/active tissues form CO2 –> HCO3-
9
Q
how does reduced pH affect structure of Hb?
A
- reduced pH (more H+ ions) allows formation of more interactions and increased stabilization of the taut state (delivers O2 to tissues)
10
Q
describe the function of carbonic anhydrase
A
- carbonic anhydrase promotes the function of carbonic acid from CO2
- H+ ions protonate Hb; forms positive charges
- Allows formation of additional salt bridges
- stabilizes the taut form of Hb; promotes O2 delivery to tissues
11
Q
describe the carbamamino hemoglobin
A
- CO2 may react with the amino terminus of the alpha-chains to form carbamamino hemoglobin
- allows formation of additional salt bridges and also the release of H+ ions to strengthen the Bohr effect
12
Q
describe fetal hemoglobin
A
- fetal Hb binds to 2,3-BPG less tightly so it has slightly higher O2 affinity
- persistence of fetal Hb
- benign condition
- if able to induce, may be a “cure” for B-thalassemia or for sickle cell
13
Q
describe HbA1C
A
- the N-terminus of the B-globin may be glycated
- glycation is a non-enzymatic spontaneous rxn
- glycosylation is enzymatic and regulated by the body
- can be used to monitor blood glucose levels over the previous 120 days (life span of RBC)
14
Q
contrast the role of Hb in the lungs and tissues
A
- lungs: CO2 and H+ leave Hb, which promote the relase of 2,3-BPG as O2 binds
- r-state favored
- tissues: CO2 and H+ bind, promoting the binding of 2,3-BPG which releases O2
- t-state favored
