Flashcards in Lecture 8-Seidler: Hemoglobin Deck (40)
Structure of hemoglobin
-Porphyrin ring and Fe+2
hemoglobin vs myoglobin graph
Myo-hyperbolic and; hemo=sigmoidal
One cell proliferates to 2,000 cells; 120 lifespan, brutal life d/t squeezing through capillary beds-often call cell remnants. Monitoring RBC structure is a good indication of health.
How much heme in hemoglobin?
37% heme in hemoglobin
Tetramer- 4 Globin chains...8 total Alpha helices (A-H) alpha 1 and 2 and B 1 and 2 make up the 4 Globin chains,
Sickle cell anemia
Substitution from glutamic acid to valine on the 6 helix. This is a nonconservative substitution.
Why can't Hemoglobin be B sheets?
B sheets are sticky and we want to decrease the affinity of the transport molecule to offload O2 into the tissue....not to keep the O2 on the transporter.
Embryonic Hemoglobin types:
Zeta and epsilon
Fetal hemoglobin types:
alpha like chains
Alpha and zeta
Beta like chains:
Epsilon, gamma, delta, and Beta
Most common adult hemoglobin:
96%: Alpha2Beta2. (Hb A)
4%: alpha2Delta2. (Hb A2)
Common fetal hemoglobin type:
Alpha 2 GAMMA2...should not see after 2 weeks life
SHows cooperativity in hemoglobin
Switch and lock: when one binding site removes O2 the rest of the sites will have decreased affinity to remove the O2....same is true for taking up O2....thus, cooperatively, the hemoglobin functions (similar to all or none-protein folding)
Ppressure and O2 taken up
W/ inspiration, the Ppressure difference down the gradient pushes the O2 to the hemoglobin(lower pressure)
Switch and lock
This is when the helix has conformational change d/t binding or unbinding of O2-15 degree turn.
-Heterocyclic tetrapyrrole; planar and hydrophobic; bound to Globin chain.
-One Fe+2/chain; 4 tetramers civil molecule---O2 binding
WHat state is Fe in on Porphyrin ring?
+2....+3 would be a dysfunctional protein...
What other molecule can bind to Fe in hemoglobin?
CO and O2 compete for the binding space
F8- this is the 5th coordination site. This is where the Fe+2 ion binds.
E7: This is the 6th coordination site: this HIS is where O2 will H bond w/ the distal histidine. ALSO FUNCTIONS AS REGULATOR TO KEEP FE+2 TO BECOME FE+3...CONTROLS THE INTRINSIC REACTIVITY OF HEME
Transport Oxygen and CO2 in and out of the body
MEchanism of O2 binding:
Fe+2 :O2 binding site, cooperativity, reversible binding, allosteric control
Sigmoidal mechanism of O2 dissociation indicates:
During exercise the offloading effects of Hemoglobin can drop by:
Cooperativity in Hb
Conformational change in one subunit induces a conformational change in another--inter subunit interactions
Structure of myoglobin:
-Myoglobin is a monomer
-one Globin chain-different gene
Myoglobin has higher affinity b/c:
You want higher O2 affinity in muscle for for mitochondria...final O2 sink...