Hemoglobin I & II Flashcards
Basic equipment of Hemoglobin’s binding site
beta-2 F8 contains proximal histidine
beta 2-E7 contains distal histidine
alpha1 C chain interfaces “elbow point” on alpha chain, causes conformational alteration in the other subunits to be optimally primed for oxygen uptake
process of oxygen uptake initially occurs in beta2, F helice
heme group containing iron
Bonding patterns in hemoglobin
beta 2 F8’s proximal histidine chelates Fe2+’s 5th coordination site, pulling it .4 angstroms from the plane
oxygen binds to Fe2+’s sixth coordination site
Oxygen forms superoxide stabilized by distil histidine donating a hydrogen bond to prevent free radical
Fe in 3+ state is called methahemoglobin, usless molecule
when when you find heme’s iron group in a +3 valence state, and what do we call this group?
oxidizing agents (toxins )
methemoglobin
Iron in heme and free iron
Iron is stabilized in the 2+ state in heme, and momentarily oxidized to 3+ during the binding of oxygen which pulls it BACK INTO THE PLANE of the porpheryn ring
3 blood plasma proteins, site functions and why
haptoglobin: grabs hemoglobin
hemopexin: grabs free heme in blood
transferin: grabs free iron
iron is toxic, catalytically producing free radicals in the blood.
hemoglobins fetal to adult
fetuses have alpha gamma (ay) hemoglobin subunits
by one year gamma has been “shut down” and betas have been activated.
Typically oxygen binds to ____ first
beta, F8 proximal histidine
Sicle Cell: why
amino acid substitution between a hydrophobic valine (interior) and a hydrophilic amino acid (glutamine)
Sicle cell: where
beta chain
Beta chain diseases are typically
worse than alpha chain diseases
Hb S
sicle cell anemia, Hb A wildtype
How does methemoglobin relinquish its oxygen?
methemoglobin reductase, which is an NADH: it contributes electrons to the iron and reduces it
the distal histidine also assists
Allosteric activity of hemoglobin
conformation change due to stimulation at a site other than oxygen binding site
can inhibit or stimulate oxygen
Hemoglobins conformation states
R state (oxygenated) and T (deoxygenated)
Homologous Proteins to Hemoglobin
myoglobin: takes oxygen FROM rbcs, does not supply them.
has a higher affinity for oxygen than RBCs
Allosterics: H and CO2
protons bind to hemoglobin —> T conformational state (BOHR EFFECT) Low pH
CO2 bind to hemoglobin —> T state
pH of a muscle cell is
between 7.2-7.4, very acidic environment
Haldane Effect
Oxygen drives off the CO2 and H in the lungs
Glycolysis does what
produces H in the cells
2,3-BPG
will be elevated in response to living in a higher altitude
negative allosteric effector: enhances offloading of oxygen
H–Hb–CO2 is the result of the
bohr effect (rightward shift)
result of mass action
more O2 in tissues, more CO2 in RBCs
O2-Hb is the result of the
Haldane effect, O2 diffuses into lungs and replaces CO2 and protons
Evolutionary Time Line of Hemoglobin: from Leg-to Hemo
DIVERGED 800+ million years ago leghemoglobin/myoglobin/hemoglobin alpha/hemoglobin delta
DIVERGED 500+ million years ago
myoglobin, alpha and beta hemoglobins
DIVERGED 350+ million years ago
Hemoglobin alpha from hemoglobin beta
Hemoglobin A has
alpha2beta2 adults
Hemoglobin A2
alpha2delta2 adults, 2%
Hemoglobin F
gamma chains (fetal)
What is the mutation in the hemoglobin F that allows it to have a higher affinity for oxygen than hemoglobin A?
residue that binds 2,3 diphosphglycerate
Heme
heterocyclic tetrapyrole structure (porphyrin ring) with an iron molecule in the middle
planar AND hydrophobic
bound to globin chain
What kind of cooperativity does myoglobin have?
the OPPOSITE of cooperativity: it’s just ONE subunit, a different gene, and holds on to oxygen
What molecules are in the RBC?
1) hemoglobin
2) molecules involved in pyruvate
3) methemoglobin reductase
4) enzyme responsible for converting intermediate in glycolysis from 1,3-DPG to 2,3-DPG
Which way will the oxygen curve shift in the presence of 2,3-DPG
rightward, reduced affinity for oxygen
RBCs need atp? if so, why?
work, keeping out sodium and calcium
