Hemoglobin Structure and Function Flashcards
what is the size and shape of red blood cells
-biconcave discs
-7.8 diameter, thick rim is 2.5 microns, thin center is 1 micron; average volume is 90-95
RBC’s cytoskeleton proteins confer large deformation capacity to RBC’s allowing them to…..
squeeze through capillaries
can RBC counts be increased?
yes when stimulated (higher altitudes)
sites of erythropoiesis and production of RBCs by age
-yolk sac: first few weeks of gestation
-Liver (spleen & lymph nodes): mid-trimester
-bone marrow: last month of gestation through adulthood
what is the lineage of red blood cells
proerythroblast
basophil erythroblast
polychromatophil erthroblast
orthochromatic erythroblast
reticulocyte
erythrocyte
usually devoid of nucleus, mitochondria, golgi apparatus, ribosomes, and other organelles
erythrocytes
retain a small amount of ER and mRNA, supporting continued hemoglobin synthesis
reticulocytes
what is the life span of RBCs
120 days
RBCs ATP is generated by ___________
glycolysis
Normal hemoglobin concentration is _______ per 100mL of packed red blood cells
34 g
hematocrit
packed cell volume
what is normal hematocrit
40-45% (slightly lower in women)
normal hemoglobin is _____per mL of blood
14-15 g
O2 carrying capacity is 1.34 mL/g Hgb or _________________/100mL of blood
19-20 mL O2
what are the steps for formation of hemoglobin
1) 2 succinyl-CoA + 2 glycine —> pyrrole
2) 4 pyrrole—> protoporphyrin IX
3) protoporphyrin IX + Fe++ —-> heme
4)heme + polypeptide—> hemoglobin chain (alpha or beta)
5) 2 alpha chains + 2 beta chains—> hemoglobin A
there are several types of globin chains resulting from…..
differential gene expression
what is the predominant form of hemoglobin in adults
hemoglobin A
each globin chain is associated with one heme group containing one atom of ____
iron Fe2+
each of the four iron atoms can bind loosely and reversibly with ____________
one molecule/2 atoms of oxygen
how many oxygen atoms/molecules can each hemoglobin molecules transport
8 atoms/4 molecules
Hemoglobin affinity for O2 changes accordign to the number of ?
heme groups already bound to O2
each O2 molecule that binds to hemoglobin facilitates …..
the binding of the next O2 molecule
tense state (T)
deoxygenated
relaxed state (R)
oxygenated
what are the important factors that contribute to the modulation of hemoglobin affinity for O2 by favoring one state over the other?
carbon dioxide
hydrogen ions
2,3-diphosphoglycerate
the affinity of hemoglobin to bind to O2 is inversely related to both ……
acidity (pH) and concentration of Co2 in the surrounding environment
binding of Hydrogen ions to the polypeptide portions of hemoglobin favors hemoglobin conformation in what state?
tense (T)
what are the basic premises of the Bohr Effect?
when CO and H+ levels increase, hemoglobin is altered in 3 ways:
-hemoglobin binds with CO2 to form carbaminohemoglobin (HbCO2)
-Hb becomes protonated (HHb+)
-Hb’s affinity for oxygen decreases and Hb-O2 dissociation curve shifts to the right
2,3-DPG is formed during the conversion of _________________to __________via an alternative pathway to the main glycolytic pathway by which ATP is generated during glycolysis.
glucose to lactate
What happens when 2,3-DPG binds to the central charged cavity of deoxyhemoglobin?
stabilizing hemoglobin in the T state, this reducing affinity for O2
what happens when there is high O2 in the lungs?
it displaces CO2 and H+ and reduces available binding sites for 2,3-DPG since Hb shifts to relaxed state
what happens when there is high CO2 and H+ in the tissues?
O2 is displaced and it increases available binding sites for 2,3-DPG since Hb shifts to T state
What factors can alter Hb affinity for O2, CO2, and 2,3-DPG and affect Hb main function to transport O2 and assist in acid-base regulation?
-living in high altitudes (increased 2,3-DPG levels)
-heart failure (reduce O2 delivery to tissue & lead to lung congestion
-asthma
-heavy smoking
-genetic variants that alter Hb affinity for O2 or its modulators
what are naturally occurring variants that alter Hb-O2 dissociation curve?
-HbF has low affinity for 2,3-DPG bc they dont have the binding site, thus has a higher affinity for O2/double Bohr affect
-alpha or beta Thalassemias: reduced production of globins due to genetic deletion of the gene alleles that form these globins, with varying degrees of disease severity
-AA substitution in critical portions of Hb
-methemoglobin (MetHb) can be acquired or inherited and results in increase levels of heme with Fe3+ (cant bind O2) instead of the normal Fe2+
-sickle cell anemia
describe the mutation that causes sickle hemoglobin (HbS)
-a single nucleotide substitution (A to T) in the codon for amino acid 6, which converts glutamic acid codon to valine codon
Hemoglobin of homozygous individuals forms elongated crystals when exposed to ___________________; this leads to vascular occlusion and hemolysis
low oxygen
what does the double Bohr effect in fetal hemoglobin allow for?
O2 can pass more easily from maternal HbA to fetus HbF in placenta bc of the higher affinity for O2
what is the root of carbon monoxide poisoning?
carbon monoxide has 250 times higher affinity for the heme group than O2
how does CO shift the Hb-O2 dissociation curve?
shifts the curve down and leftward and reduces the plateau
what is the role of Hb in CO2 transport and acid-base regulation?
the majority of CO2 travels as bicarbonate (HCO3) and H+ which are converted to H2O and CO2 by carbonic anhydrase
describe myoglobin
-has higher affinity for O2 and serves mainly as a reservoir of O2 for exercising muscle
-hyperbolic dissociation curve (releasing O2 when O2 levels are low in tissues)
-helps with intracellular O2 transport (from plasma membrane to mitochondria)
how does the structure of myoglobin differ from that of hemoglobin
myoglobin is only a single subunit protein compared to the 4 subunits in hemoglobin
haldane effect
O2 displaces Co2 from hemoglobin
in the tissues
bohr effect
CO2 and H+ displace O2 from hemoglobin
in the lungs
