Myoglobin and Hemoglobin Flashcards
How long will you see embryonic Hb present?
~ 1 week post-conception until birth
CO + heme in Hb (HbCO)=
Carboxyhemoglobin –>forms more readily than oxyhemoglobin (HbO2)
What is the most common Hb variant associated with pathology in the US? What disease does it cause?
Bs mutation; sickle cell anemia
Methemoglobinemia is characterized by
Chocolate blood and cyanosis
What are 4 substances that competitively bind to the Fe-binding site in heme and which one binds up to 300x stronger than O2?
- Cyanide (CN-)
- Carbon monoxide (CO)
- Nitrogen dioxide (NO2)
- Hydrogen sulfide (H2S)
CO binds very strongly to Hb
Mutations in cytochrome b5 reductase cause hereditary ________. What is the purpose of this enzyme?
This enzyme uses NADH generated through glyceraldehyde phosphate dehydrogenase (glycolysis) to reduce Fe3+ in methemoglobin to Fe2+ thereby reversing formation of Fe3+.
alpha2 delta2
HbA2
2,3-DPG (same as 1,3-BPG) is present in all RBCs in adults and is produced in RBCs when _____ is abundant and stabilizes the __ state
glucose; T
Most CO2 enters RBCs and 15 % of the time forms _____ _____with Hb or is converted to H2CO2 (85% of the time) by _____ ______ then dissociates to HCO3- and H+.
carbamate adducts; carbonic anhydrase
alpha2 gamma2
HbF
p50 of Hb
26 torr
At position 6 of the B-globin gene, the amino acid change from ___ to Val6 confers sickle cell anemia
Glu6
Sigmoidal binding curve = what type of cooperativity?
Positive; in Hb
Alveolar partial pressure of O2 is ___ while the alveolar partial pressure of CO2 is ___
100 mmHg; 40 mmHg
In the lungs, high pO2 drives binding of O2 to Hb, release of H+, and formation of H2CO3 (carbonic acid). Carbonic acid equilibrium favors synthesis of CO2 and H2O. What is the name of this effect?
Haldane Effect
p50 of Mb
2.8 torr
Fe-protoporphyrin IX =
Heme
Weak ____ interactions are between the a1B1 and a2B2 heterodimers in Hb
Polar
Myoglobin is made up of primarily what conformation of protein?
Alpha helices - 80%
Hb Bart’s disease or hydrops fetalis is formed by how many alpha globin deletions?
4
O2 binds to Hb _____
Cooperatively
What are some causes of hereditary methemoglobinemia?
- Mutations in the Pentose Phosphate Pathway, especially G-6-phosphate dehydrogenase deficiency
- Glutathione- normally reduces reactive oxygen species
- Mutations in cytochrome b5 reductase (NADH-dependent methemoglobin reductase)
Shifting O2 binding curve to the right means there is a higher/ lower affinity for O2
Lower
In RBCs, protons released by the dissociation of H2CO3 bind to Hb and favor the T state, favoring O2 release. What is this effect?
Bohr effect
Carbamate adducts stabilize the __ conformation of Hb in the tissues and when reaches the lungs the high PO2 and low PCO2 causes a reversal of this reaction leading to expiration of CO2
T
Type of Hb that makes up 97- 98.5% of total Hb in adult
HbA; a2B2
HbF has a higher/lower affinity for oxygen than HbA. Why?
Higher; Binds 2,3-DPG poorly (gamma chains do not bind as well as beta chains in HbA) which shifts the curve to the left –> the O2 that is released from the mother’s HbA is bound to HbF and transferred to fetal tissue
a-like globin genes are found on chromosome __
16
R (relaxed) form of Hb is the _____ form
Oxy form (O2 binding)
Low pH favors O2 ____ to Hb and shifts the curve to the ____
Binding; right
Movements of the proximal and distal _____ cause their attached a-helices to move that causes a conformational change at the interface of each aB dimer in the Hb molecule
histidines
Which subunits bind together with strong hydrophobic interactions in Hb?
a1+B1 a2+B2
Disease characterized by 3a globin gene deletions that forms a B4 tetramer
HbH disease
O2 is a ____ allosteric regulator of Hb O2 binding
Positive
Type of Hb that is found in patients with homozygous sickle cell anemia that is also found in neonates
HbF
T (taut) form of Hb is the _____ form
Deoxy (O2 release)
Heme, chrolorphyll, Vit. B12 are all _____
Porphyrins
In order for O2 to still bind Hb when 2,3-DPG is present, what is required?
Higher pO2
B-like globin genes are found on chromosome __
11
Type of Hb that makes up 1.5 - 3% of total Hb in adult
HbA2
Addition of 2,3-DPG would cause the O2 binding curve of Hb to shift to the ____
Right; allowing for more O2 to dissociate from Hb to supply O2 to the tissues operating at high metabolic rate
How many O2 molecules does myoglobin bind?
1 O2
Hb binds ___ O2
4
______ rings form coordinate covalent bonds to Fe2+ in heme
Pyrrole
z2e2 or a2e2 or z2g2
HbE (embryonic)
Hemoglobin is made up of 2 __ chains and 2__ chains
2 alpha 2 beta
The binding curve of Mb is ____ while the binding curve for Hb is ____
Hyperbolic; sigmoidal
COPD, high altitudes, chronic anemia, and pregnancy causes an increase/decrease in 2,3-DPG
Increase
Which form (deoxy or oxy) of HbS forms long polymers within the RBC that causes the sickle shape and short lifespan?
Deoxy
High pH favors O2 ____ to Hb and shifts the curve to the ____
Relase; left
Individuals homozygous for the Bs mutation, or heterozygous for the Bs and a B-thalassemia allele, produce significant amounts of _______ and have sickle cell disease
HbS (a2Bs2)
PCO2, pH of blood and tissues,a and 2,3-DPG act as _____ allosteric regulators
negative; interaction at one site on Hb decreases O2 binding to heme at some distance from binding site of allosteric regulator
Heme belongs to the class of pigments called _______
Porphyrins
Type of Hb that is the major Hb from ~ 1 month gestation until near birth; ~40% at birth
HbF
