Oxygen transport Flashcards
The oxygen transporter of muscle
Myoglobin
Myoglobin contains a prosthetic group called a _____
heme molecule
Myoglobin is comprised of _____ aa residues
153
The proximal histidine residue (___) forms a _____
The proximal histidine residue (F8) forms a direct ligand to the iron
The prosthetic group of myoglobin and hemoglobin, heme, is ______
in a deep, non-polar pocket
This sequestering of iron from water (through the hydrophobic pocket ) helps maintain the ______
Fe 2+ state
Carbon monoxide (CO) bound heme is also _____ (color)
bright red
Since histidine is attached to the whole helix, when oxygen binds the iron, the _____
whole helix moves (changes conformation)
Myoglobin can only carry _____ (number) O2
1
Impact of change in structure of myoglobin due change in oxygenation state
None
Oxygenated heme is ____ (color)
bright red
Oxidized heme is ____ (color)
brownish
deoxygenated heme is_____ (color)
more blue
Hemoglobin comprises of _____ _____ subunits and _____ _____ subunits
2 alpha and 2 beta subunits
Hemoglobin (HbA) is a ____ of ab units
dimer
Hb is a ____ oxygen binder than myoglobin
weaker
Hill coefficient tells you _____
The level of cooperatively
n>1 means ______ cooperativity.
positive cooperatively=binding of one ligand promotes binding of another.
n=1 means _____ cooperativity.
no
n<1 means___
negative cooperativity
Hemoglobin exists in __ and __ forms
T and R
Which form (T/R) has no oxygen bound
T
Which form (T/R) has oxygen bound
R
Which form (T/R) is more stable, and why?
T, because it contains more electrostatic and hydrogen bonds or “tense”
Both _____ and _____ reduce the O2 affinity of hemoglobin. These effectors are called____
H+ and CO2. Allosteric effectors
Both H+ and CO2 allow hemoglobin to deliver _______
more oxygen to actively metabolizing tissues
Hb releases O2 in muscles upon binding of
CO2
Hb releases CO2 in lungs upon binding of
O2
_____ lowers the affinity of hemoglobin for oxygen.
Bisphosphoglycerate (BPG)
Normal blood concentration of BPG
5mmol/L
BPG rises under _____, allowing oxygen to be efficiently delivered to tissues
low oxygen conditions
In HbA, BPG binds to ______
a pocket formed by the beta subunits (many positive charges)
Fetal hemoglobin (HbF) is _______. Adult hemoglobin (HbA) is ______.
Fetal hemoglobin (HbF) is alpha2-gamma-2. Adult hemoglobin (HbA) is alpha-2-beta-2.
HbF and HbA are VERY similar in sequence, structure, and function, except in their ability to bind _____
BPG
BPG binds with lesser affinity to HbF, because
HbF has fewer positive charges in its corresponding pocket than the pocket made by the two beta subunits on HbA
Because HbF binds BPG less well, it ______
binds oxygen with higher affinity
2 diseases of hemoglobin
- methemoglobinemia
2. sickle-cell anemia
Nonpathological substitution
Mutations that have no effect on hemoglobin function
Hemoglobin S
disrupt hemoglobin structure or function
Characterized by insoluble Hemoglobin (HbS). Result is clogging of capillaries and
general organ damage causing pain
Sickle Cell anemia. 1 in 13 African Americans affected
The molecular defect in HbS of sickle cell anemia is
A point mutation converting glutamate to valine on the exterior of the beta subunit
Sickle cell mutation can be detected using
electrophoresis
Sickling is made worse by
decreased oxygen
A _____ is formed in both HbA and HbS when in the deoxy form
hydrophobic hole
A _____ is present on the b subunit of HbS in both deoxy and oxy forms
hydrophobic knob
The deoxy form of HbS can form ______
long polymers
Treatment of Sickle Cell Anemia
- Antibiotic therapy (to prevent secondary infections)
- Hydroxyurea (stimulates the production of HbF)
- Bone marrow transplantation (replaces HbS with HbA)
- Gene therapy (Phase I/II)
Methemoglobinemia
Heme groups become +3 ad cannot carry oxygen
2 ways to develop methemoglobinemia
Inherited: Mutations in heme-binding pocket of Hb can promote HbM
Environmental: Ingestion of nitrates and nitrites can promote HbM.
Clinically present with shortness of breath, cyanosis, mental status changes
Methemoglobinemia
Methemoglobinemia is diagnosed by
the absorption spectrum of the blood (peak at 630nm)
Ways to treat the disease:
Reducing agents (such as Vitamin C and methylene blue)
Oxygen binds to
heme
Carbon dioxide binds to
site outside of heme
Carbon monoxide binds to
heme
BFG binds to
a pocket formed by the &beta-subunits
H+ binds to
histidine and the N-terminal α-amino groups (of the α-subunits)
