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what is the relaxed state of hgb
- "oxyhemoglobin"
- has a higher affinity for oxygen than T form, whether or not oxygen in present
- a dipeptide rotates opening a 15 degree cleft
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what is a tense state
- "dexoxyhemoglobin"
- stabilized by salt bridges between chains. when oxygen binds, Hgb transforms to R-form and salt bridges are disrupted
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describe the process of cooperativity in Hgb
- bound O2 pull iron atom into the plane of the heme
- movement of the iron pulls the proximal his
- movement of his disrupts salt bridges and frees up subunit, transforming into R-state
- binding of O2 to second subunit triggers same sequence, enhancing binding to third subunit
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what effect does proton, CO2, and 2-3 BPG all affect Hb
- incrs affinity for O2 in lung
- decrs affinity for O2 in tissues
- all cause O2 affinity curve to R-shift
- all induce relaxed to tense transition through salt bridge formation
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what is the bohr (proton) effect
- when O2 binds to Hgb it makes Hgb sensitive to physiological pH changes.
- contracting muscle: lactic acid is produced causing [H+] to increase, which promotes O2 dissociation
- H+ antagonizes the binding of O2 to Hgb
- in lungs higher pH increases affinity of Hg for O2
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describe how the Bohr effect is in terms of R and T
- H+ induces R to T conversion
- His becomes protonated giving it a (+) charge.
- induces salt bridge formation with Asp a characteristic of T state
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describe the role of CO2 in hemoglobin
- CO2 is byproduct of metabolism. Accumulation of CO2 is a result of active metabolism and increased O2 requirements by the tissue
- CO2 lowers the affinity of Hb for O2, so that in the tissues O2 is released.
- in the lungs CO2 is kept lower by expiration, increasing affinity of Hgb for O2
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describe carbon dioxide in terms of R and T
CO2 binds to the N terminus of Hgb and forms a salt bridge, stabilizing the T state
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describe the role of 2,3 BPG
- 2,3 BPG is produced in the RBC from the metabolism of glucose
- BPG lowers the affinity of Hgb for O2
- accumulation of BPG is a characteristic of active metabolism and increased O2 requirements by the tissue
- in the lungs, when O2 is bound the caivty where BPG binds becomes small, thus increasing affinity for O2 in lungs
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describe the role of 2,3-BPG in terms of R and T
the neg BPG interacts with + charged residues (Lys, His) crosslinking the B-subunits. This stabilized the T state
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What are the protein subunits of fetal hemoglobin
gamma and alpha
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describe how fetal Hgb has a higher affinity for O2 than adult Hgb
- gamma subunit has more Ser than His, this decreases salt bridge formation
- results to more relaxed state.
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what are isoforms and give and example
- isoforms: distinct forms of a protein that have the same function but are found in different tissues
- fetal Hgb and adult Hgb
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