Hemoglobin and Myoglobin Flashcards
Myoglobin is a ________ in _______. It stores _________ in _______ and delivers ___ to _______.
Binds ______ at ______ levels.
oxygen carrier in muscle cells
O2 in muscle cells, delivers it to mitochondria
O2 at low levels
Hemoglobin is a _________ in _____. It binds ______ in ________ and release _______ in the _______.
It is sensitive to small changes in ______ allowing for ______. It also carries ________ from the ________ to the ____.
oxygen carrier in blood
O2 in the lungs
O2 to the tissues
Oxygen allowing for maintenance of homeostasis
CO2 from the tissues to the lungs.
RBC’s in lungs have high levels of O2 this favoring binding to _____. Lower _____ in RBC’s in muscles triggers the _________ of _______ from ____. In muscle, ____ will take up _____.
Hb, O2 levels
release of O2 from Hb. Mb, O2
The _____ can oxidize fuel during the ______. They consume ______ and release _______. When CO2 is release into the blood is is transported as ____ or ____.
CO2 is released by the _____.
mitochondria, ETC
O2, CO2
HCO3 or Hb-CO2.
Lungs
Myoglobin has a _____ protein structure while hemoglobin has a _______.
Myoglobin has a___ group while hemoglobin has ______ because it is made up of ______ each with _______..
tertiary, quaternary
1, 4
4 polypeptide chains, 1 heme group
Heme is an ____ of ______ and ___ where _____ binds.
It contains a ___ with a single __ that can form ________.
4 bonds have _________. With the other two having ________ and _______ respectively.
active site, Mb and Hb, O2
porphyrin ring, Fe , 6 coordinate bonds
pyrrole nitrogens in the poryphryin ring plane
imidazole nitrogen from a histidine in polypeptide chain
ligand (O2 or CO2)
Imagine a rectangle representing the porphyrin ring. 4 bonds extends from the Fe towards the “corners” of the rectangle. The imidazole nitrogen with histidine is protruding from the top while the ligand is protruding from the bottom.
O2 binds to _______ in Mb and Hb. Fe__ does NOT bind to ______.
Fe2+ (reduced).
Fe3+ (methemoglobin HbMet)
Mb has a _____ affinity for _____. It will release very little O2 between ____ and ________.
O2, 10 and 100mmHg
Hb has a _____ affinity for ________. It has __________ and a _____ shape on a linear plot.
low, O2
positive cooperativity, sigmoid curve
Features of Positive Cooperativity
- 2 ligand binding site
- 2 receptor conformations with different affinities for ligand
- First ligand bound has lower affinity (larger Kd) than subsequent Ligands.
- The hill slope is more than 1 and less than the number of sites.
- Occupancy is more sensitive to changes in ligand concentration.
There are 2 conformations of Hb. _____ and ___.
Describe them.
T or Taut has low affinity for O2 and is prevalent at low O2 in tissues.
R or Relaxed has a high affinity for o2 and is prevalent at high O2 in lungs.
Hb is made of a/b dimers with dimers being in varying states
When O2 is unavailable, Fe is ______ of ______ and Hb is stabilized in the _______.
When O2 binds, the Fe is ______ into the _______ which stabilizes the ________. This increases _____________.
out , the heme plate, T-conformation
pulled into the heme plate, conformation, affinity for O2 at other sites.
Mb-O2 binding is ______.
Hill Coefficient:
Response in changes to O2:
Hb-O2 binding is ______.
Hill Coefficient:
Changes in response to O2:
non-cooperative
=1
Low response to changes in O2
positive cooperativity
>1
Sigmoid Curve
Very responsive to changes in O2
O2 is an _________ of Hb because it _____________ and increases ___________.
homotropic allosteric modifier
binds to the active site, increases O2 affinity at other active sites
Heterotropic inhibitors _________________ while activators __________.
stabilize the low affinity or T-state
stabilize the high affinity or R-state.
_________,______ and ______ are ________ of O2 binding to Hb because they establish the T-shape.
heterotropic inhibitor
H+, Co2, 2,3BPG
How does an increase in H+ decrease O2 binding to Hb?
When H+ is lowered, the ionic bond is ________ thus making the _____________ more stable.
H+ does not bind to the Fe on heme which is the active site for O2.
It binds to His146 is the beta subunit to stabilize an ionic bond between His146 and Asp94 in the T-state.
lost, R-state
An __________ in H+ can lead to a _______ in O2.
increase, decrease
How does an increase in CO2 decrease O2 binding to Hb?
CO2 forms a covalent bond with the terminal amine group of Hb. This reaction release H+ .Because H+ binds to the His146 in the beta subunit Hb to form an ionic bond with Asp94.
Describe the Bohr Effect
- Metabolizing tissues generate CO2 via the Krebs cycle. RBC’s convert CO2 into H2CO3-. H+ binds to Hb when H2CO3 dissociates into H+ and HCO3-.
H+ binds to Hb and O2 is released for tissues to use. Positive cooperativity allows for R-state to be stabalized.
How does an increase in 2,3 BPG decrease O2 binding to Hb?
BPG is a by product of anaerobic glycolysis and is the RBC’s only support because they contain no organelles.
When BPG is high, it weakens O2 binding to Hb allowing for it to be dispersed to the tissues.
CO or ______ has _____________ and _______ at the Hb active site. It _______ with O2 for the ________.
carbon monoxide,
non-allosteric and allosteric
competes, O2, heme site in Hb
CO or _______ causes _____ of yearly poisoning death. IT is produced from _____ of ______ such as ______.
carbon monoxide, 1/2
incomplete combustion of organic matter, engines, furnace, generator, lawn mower, gas grill, tobacco smoke
Non-allosterically, CO ___________ with _____.
Allosterically, CO _______ increases ______________. This ______.
competes with O2 binding at active site
bound at active site, O2 binding at other active sites. This will stop O2 from releasing when levels get to low.
Hb A
Major Adults Form A2B2
Hb A2
Minor Adult Form A2D2
Hb F
Minor Adult Form A2G2
Major Hb in fetus and newborn. Much higher affinity for O2 than HbA and does not bind well to BPG
Does HbA or HbF have a higher affinity to O2?
HbF
HbS
Sickle Cell resulting from a B6 Glu —> Val changes.
HbM
B58 His —-> Tyr creating Methemoglobin (Fe3+ heme that cannot bind oxygen).
What Hb is prominent until birth. After?
HbF and then HbA later
Sickle Cell Anemia is Hb___
Thalassemias is the __________. While this mutation on _____ can protect from _______, on two alleles it results in ______.
It is the result of a _______ mutation on the ______ where there is a switch from ______ to _____ at the _____ position. Results in ____.
HbS
impaired synthesis of alpha or beta chains
one allele, malaria
two alleles, SS
missense, beta globin, Glu to Val at the 6th position
anemia
Describe how the mutation in Sickle Cell anemia causes the disease.
In T-conformation, Valine on Hb exposes a hydrophobic path. Under anoxic conditions, the polymerization of this varied structure causes the sickle cell.
The sickle shape occludes blood blow and free heme and broken RBC’s lead to inflammation. Can lead to ischemia or necrosis due to lack of blood flow.
If RBC’s aggregate what are some dental issues that could occur?
Vaso-occlusion can cause
Osteomyelitis, Orofacial Pain
Atrophy lingual papillae
Pulpitis/necrosis
Mental nerve neuropathy
Aslpenia-impared immune systems
If hemolysis occurs what are some dental issues that can occur?
Anemia - Mucosal Pallor
Free Heme- Gingival Discoloration
RBC membrane,Free Heme - Inflammation
What is mucosal pallor?
Due to chronic hemolysis, decreased RBCs (anemia)
Mucus membranes are lighter than normal
What is lingual papillae atrophy?
Vaso-occlusion, decreased blood flow
Smooth tongue- bumps on tongue are lost
