Hemoglobin Flashcards
T/F Oxygen is soluble in water
F, it isn’t that’s why you need hemoglobin
Major form of hemoglobin in adults
Hb A
Hb A composition
4 polypeptide chains (2 alpha and 2 beta held together via non-covalent interactions)
. Each chain has regions of alpha-helical structure and hydrophobic heme binding pocket
Hemoglobin tetramer
Composed of 2 identical dimers, alpha-beta 1 and 2
. Chains in dimer held by hydrophobic interactions
. Dimers held together by polar bonds
Deoxyhemoglobin
. T (taut) structure
. 2 alpha-beta dimers interact via ionic and H bonds that constrain movement of polypeptide chain
. Low oxygen affinity form
Oxyhemoglobin
. R (relaxed) structure
. Binding of O2 to hemoglobin causes rupture of some polar bonds between alpha-beta dimers allowing movement
. High-oxygen-affinity form
T/F there is a small amount of oxygen dissolved in plasma blood
T, but it is physiologically insignificant
How many O2 molecules can Hb bind?
4, one at each heme
Pulse oximetry
Noninvasive, indirect method of measuring O2 saturation of arterial blood based on light absorption difference by R and T Hb
Partial pressure needed to achieve half-saturation of binding sites (P50)
26 mmHg for Hb, 1 mmHg for myoglobin
How many O2 molecules can myoglobin carry?
1
Myoglobin O2-dissociation curve shape and why
Hyperbolic shape reflecting that myoglobin reversible binds a single molecule of O2
What is Mb designed to do?
Bind O2 released by Hb at low pO2 in muscle
. Releases o2 w/in muscle in response for O2 demand
When is oxygen dissociation curve Hb steepest and why?
. At O2 concentrations that occur in tissue
. Permits O2 delivery to respond to small changes in pO2
What shape O2-dissociation curve for Hb?
Sigmoidal, indicating subunit cooperative binding
. Allows unloading at areas of low pO2
Cooperative binding
. Binding of an O2 molecules at 1 heme inc. O2 affinity of remaining heme groups in same tetramer
. Heme-heme interaction
Allosteric effectors
. affects the ability of Hb to reversible bind to O2
. PO2
. PH in environment
. PCO2
. 2,3,-BPG
. Bind to one site on Hb and affect binding of O2 to heme groups at other sites on Hb
T/F Myoglobin is NOT effected by allosteric effects
T
Net effect of structural changes of heme groups
Affinity of Hb for the last O2 bound is 300 times greater than 1st bound O2
Where is O2 loaded and unloaded onto Hb
. Loaded in lungs where [O2] is high and Hb is saturated
. Unloaded in peripheral tissues for oxidative metabolism
Bohr effect
. Release of O2 from Hb enhanced when pH is lowered/when there is increase pCO2
. Dec. pH and inc. pCO2 shift curve right to stabilize T form
. Inc. pH and dec. pCO2 shift the curve to the left and stabilize R
concentration of H and CO2 in capillaries of metabolically active tissues compared with alveolar capillaries of lungs
Concentration is higher in metabolically active tissues than alveolar capillaries where CO2 is released into air
Carbonic anhydrase
Coverts CO2 to carbonic acid
CO2 + H2O -> H2CO3 -> spontaneously lose H to become HCO3 + H
Major blood buffer
Bicarbonate
How does Bohr effect happen?
Ionizable groups (His side chains) that have higher pKa in deoxy Hb than in oxyHb
. Inc. in [protons] and decrease in pH causes ionizable groups to be protonated and able to form ionic bonds or salt bridges
. Stabilize deoxyHb decreasing O2 affinity
When inc. protons and lower pO2 the equilibrium is shifted _____ favoring
Right, deoxyHb
When inc. in pO2 or dec. protons, the equilibrium is shifted ____ favoring ____
Left, oxyHb
2,3-BPG
. Most abundant organic P in RBCs
. Concentration of 2,3-BPG in rbcs is approx. equal to concentration of Hb
. Synthesized from intermediate in glycolysis
How does 2,3 BPG bind and what does binding do?
. Decreases O2 affinity by binding to T Hb but not R Hb
. Stabilizes T confirmation
Where does 2,3-BPG bind?
. Pocket formed by 2 beta-globin chains in center of T form tetramer
. Pocket has many pos. Charged amino acids that form ionic bonds w/ Neg. charged P groups on 2,3-BPG
How is 2,3-BPG expelled from Hb?
Oxygenation
Which does oxygen-dissociation curve move w/ 2,3-BPG
. Presence reduces Hb affinity shifting curve right
. Helps release O2 in tissue partial pressure
When does [BPG] inc?
. In response to chronic hypoxia (COPD or high altitudes)
. Chronic anemia
How long does it take rbcs to restore depleted 2,3-BPG after being transfused from a bank?
6-24 hours
2 ways CO2 is transported as:
. bicarbonate
. Carbamate
How is carbamate carried?
. Bound to N-terminal group of Hb forming carbaminoHb
Hb-NH-COO + H
How does CO2 affect oxygen dissociation curve?
. Stabilizes T form dec. O2 affinity shifting curve right
WHen does CO2 dissociate from Hb?
Released in breath
CO binding to Hb
. High affinity
. Binds to 1+ heme sites shifting Hb to R conformation and remaining sites bind O2 that don’t have CO
. Called carboxyHb
. Shifts curve left and changes from sigmoidal to hyperbola
. Affect Hb unable to release O2 in tissues
How many times greater is CO affinity over O2 affinity?
220 time greater
How does CO toxicity result?
. Combo of tissue hypoxia and direct CO-mediated damage at cellular level
How is CO toxicity treated?
100% O2 at high pressure to dissociate CO from Hb
