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26 Cards in this Set
- Front
- Back
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Ligand
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Anything that binds specifically with a protein. Can be macromolecules (other proteins), smaller molecules (normal substrates for enzymes), cofactors, electrons.
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Cofactor
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Non-protein molecule that binds to enzyme and participates in the chemical reaction. Influences the rate.
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Globin cofactor examples
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Globins bind heme which use heme cofactors to bind iron, which in turn coordinates an oxygen molecule.
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Hemoglobin structure
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Usually a hetero-tetramer. Its two alpha (a)subunits first bind to beta subunits (B). Each aB dimer then associate to form stable and functional a2B2.
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Heme
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Porphyrin ring. Organic molecule binds metals, usually Fe++ at the center.
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Effector (activator)
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BPG weakens affinity for O2 and allows more O2 to be released into the tissues.
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pO2
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Partial pressure of O2 in atmosphere. Concentration. Units in Torr = mmHg
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p50
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Concentration of O2 at which 50% of globins (Gb) in some mixture are bound with O2.
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Hemoglobin Conformations
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T = conformation that binds O2 weakly. Good for releasing O2.
R = Conformation that binds O2 strongly. Good for loading O2. |
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Types of Hb
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Found in plasma (blood)
HbA: erythrocytes (soon after birth) HbF: fetal erythrocytes |
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Non-Hb Globins
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Mg = myoglobin, found in muscle
Nb = neuroglobin, found in brain and peripheral tissues Cb = cytoglobin, found in brain and peripheral tissues |
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Why do we require globins?
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The O2 has a low solubility in water. Atmosphere is 20% O2 and at that conc., only about 2ml O2/100ml atmo. This is not enough for resting mammal.
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How much Hb and therefore O2 is in blood?
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15g Hb/100ml blood = ~20ml O2/100ml blood. Ten fold increase from atmospheric O2 conc. alone.
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O2 requirement for humans
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260ml/min in resting adult, up to 4300ml/min in athlete.
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Structural differences between Hb and other globins
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All are folded proteins made of only alpha helices. Difference is that Mb, Nb, and Cb are monomers, while Hb is a tetramer. The subunits of the tetramer interact to stabilize different conformations. This difference alters and creates different binding affinities for O2.
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Functional differences of Hb and Mb
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The affinities for O2 of Hb and Mb differ greatly. Hb has a lesser affinity and therefore has an easier time releasing and delivering O2. Mb does deliver O2 within cells, but at a lesser rate. It is also used for storage of O2. Not much is known about Nb and Cb, but their function is thought to be more like Mb.
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2-log Rule
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If you are at the pK, it takes a one log increase in H+ to nearly fully fill the binding sites and one log decrease to comepletely unload. This applies to ALL ligand binding.
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Problem of 2-log rule for Hb
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pO2 is <130 torr in the alveoli of the lungs and needs to be 30-40 torr in the tissues. This is a 3-4 fold difference. Not 2.
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Solution to problem of 2-log rule for Hb
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Hb is allosteric and is not limited to the 2-log rule. Its p50 = 10torr while that of Mb is 0.9torr.
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Mb affinity for O2
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Mb has a constant affinity for O2 with a p50 of 0.9 torr. Its hyperbolic curve is classic for ligand binding.
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Hb affinity for O2
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The binding curve for Hb is sigmoidal and is a good example of changing affinity for O2 (poor and good). The change in affinity allows Hb to load 100% in the lungs and then unload 2 of four O2 (~60%) in the tissues. Cofactors in the blood allow this. Hypothetical models (lab) allow only 30% unbinding.
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Allosteric Effects and Hb
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Allosteric means to change shape or conformation. Effectors bind to Hb and change its conformation and therefore, affinity for O2. These compounds include, CO2, 2,3-bisphosphoglycerate (BPG), and H+.
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BPG
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2,3-bisphosphoglycerate. Binds only to beta chains but effects O2 affinity for all four subunits by increasing p50 (lowering affinity for O2).
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Temperature's effect on Hb
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Higher temps (fevers = >37 degrees C) need more O2 so affinity weakens so that more O2 can be delivered to cells. In turn, lower temps cause greater affinity for O2.
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HbF
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Fetal Hb must bind O2 with a greater affinity because it has to pull O2 from maternal Hb across the maternal/fetal barrier. Has two alpha subunits and two gamma subunits (unlike beta subunits on HbA (adult/maternal Hb). Because HbF lacks beta subunits, it does not bind BPG. BPG decreases the affinity for O2. Because HbF has no BPG, it has a greater affinity for O2.
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Bohr Effect
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Bohr effect acts to enhance unloading of O2 (decrease affinity). When O2 conc is insufficient, cells start anaerobic glycolysis and create lactic acid and therefore locally increase proton conc.
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