Hemoglobin Chapter 3 part 2 Flashcards
1
Q
2
Define methemoglobinemias ?
A
oxidation of the heme iron in hemoglobin from Fe2+
* cannot bind to O2
2
Q
Fetal Hemoglobin
* fetal hemoglobin is AKA as ? * HbF isonly synthesized during when? * how can you describe the the tetramer (chain composition)of HbF ? * fraction of total hemoglobin ? * Y chains are members of which type of gene family
A
- HbF
- fetal development
- two alpha chains and two Y chains
< 2% - B-globin gene family
3
Q
2
- Carbon monoxide
- binds tightly but reversibly to IRON (Fe2+)
- carboxyhemoglobin
- forms the R form
- relaxed form (oxygenated) high affinity for O2
- shifts to the left
- oxygen to the tissues
A
CO Binding
Hemoglobin is more attracted to \_\_\_\_\_\_\_\_ over O2 * what part of the hemoglobin does CO bind tightly ? * when CO is binded to the iron of Hb what is it called? * When CO binds to one of thefour heme sites what shape or conformation (T/ R) will it form ? * remind me what the R form is about again? * The oxygen-dissociation curve shifts (right/left) ? * in this case ( the affected Hemoglobin) is unable to unload what ?
4
Q
2
- HbF
- fetal development
- two alpha chains and two Y chains
< 2% - B-globin gene family
A
Fetal Hemoglobin
* fetal hemoglobin is AKA as ? * HbF isonly synthesized during when? * how can you describe the the tetramer (chain composition)of HbF ? * fraction of total hemoglobin ? * Y chains are members of which type of gene family
5
Q
2
- the alpha chains
- two alpha globin chains and 2 MUTANT B-globin chains
(BS) - glutamate was repaced by VALINE
- two alpha globin chains and 2 MUTANT B-globin chains
A
Amino Acid Substitution in HbS B-chains
* which gene familyappears normal in HbS ? the Alpha or the Beta globinchains ? * what chain composition is contained in HbS ? * how would you write 2 mutant B-globin chains on paper? * what has been replaced in position six
6
Q
page 32
CO2 Binding
most of the CO2 produced in metabolism is hydrated andtransported as ? some of the CO2 however are carried as ? CO2's that are carried as carbamate are bound to where ? Binding of CO2stabilizeswhich form ? what direction in the oxygen dissociation curve describes the binding of CO2as in (stabilizing T form) ?
A
- bicarbonate
- carbamate
- terminal amino groups of hemoglobin
- T form
- Right shift
7
Q
Thalassemias
* cause of thalasemia ? * thalasemmia is an imbalance in which chains ? * what type of disorder is Thalassemia ? * normal HbA have Alpha2 and Beta2 paired-describe the defect in globin chains in Thalassemia ? * the concentration of what is reduced ? * Thalassemia is caused by deletions or substitutions in one or MANY what ?
A
- hereditary* imbalance in alpha or beta globin chains* most common single gene-disorder in humansnormal HbA have Alpha2 and Beta2 and are paired partners ( in Thalasemias- either the Alpha or Beta is defective)* Hb concentration in Thal is reduced* can be caused by entire gene deletions or substitutionsof one of MANY nucleotides in a DNA
8
Q
What happens when there isexcess of Alpha-globins?
A
- cannot form stable tetramers
- unstable subunits precipitate
- causes premature cell death
Increase in
HbA2and HbF occurs
9
Q
0
- tissue hypoxia and CO-mediated damage in the cellular level
100% O2at high pressure (hyperbaric oxygen therapy)- hyperbaric oxygen therapy
- NO (Nitric Oxide)
- dilate (potent vasodilator)
- influences the diameter of blood vessels
A
- the combination of CO toxicity result from ?
- what kind of treatment can help CO poisoning?
- what type of therapy facilitates the dissociation of CO latched onto the hemoglobin ?
- In addition to O2 and CO2 and CO? what else can be caried by hemoglobin ?
- what does Nitric Oxide do to blood vessels ?
- when NO is released by RBCs what potentially happens ?
10
Q
Amino Acid Substitution in HbS B-chains
* which gene familyappears normal in HbS ? the Alpha or the Beta globinchains ? * what chain composition is contained in HbS ? * how would you write 2 mutant B-globin chains on paper? * what has been replaced in position six
A
- the alpha chains
- two alpha globin chains and 2 MUTANT B-globin chains
(BS) - glutamate was repaced by VALINE
- two alpha globin chains and 2 MUTANT B-globin chains
11
Q
2
- cannot form stable tetramers
- unstable subunits precipitate
- causes premature cell death
Increase in HbA2and HbF occurs
A
What happens when there isexcess of Alpha-globins?
12
Q
2
- HbF
- HbF
- oxygen
- lower affinity to oxygen
- positvely charged amino acids
A
2,3 BPG Binding to HbF
* under physiologic conditions which one has a higheroxygen affinity ? HbA or HbF ? * which one has a weaker binding capacity to 2,3 BPG --HbF or HbA ? * weak binding on 2,3 BPG results in higher affinity to ? * stronger binding capacity to 2,3- BPG results in ? * Y- globin chains of HbF lack what kind of amino acids that is responsible for binding 2,3-BPG in the beta globin chains.
13
Q
Define methemoglobinemias ?
A
oxidation of the heme iron in hemoglobin from Fe2+
* cannot bind to O2
14
Q
page 33
Minor hemoglobins
* what is the most abundant hemoglobin in adults? * define what a tetramer is ? * hemoglobin tetramers are composed of ? * what type of Hbis onlyformed during fetal development * what other type of hemoglobin is found in adults but in lower concetrations thanHbA?
A
- HbA
- Four subunits or monomers
two alpha-globin AND two beta-globin = 4 monomers - HbF
HbA2
- Four subunits or monomers
15
Q
2,3 BPG Binding to HbF
* under physiologic conditions which one has a higheroxygen affinity ? HbA or HbF ? * which one has a weaker binding capacity to 2,3 BPG --HbF or HbA ? * weak binding on 2,3 BPG results in higher affinity to ? * stronger binding capacity to 2,3- BPG results in ? * Y- globin chains of HbF lack what kind of amino acids that is responsible for binding 2,3-BPG in the beta globin chains.
A
- HbF
- HbF
- oxygen
- lower affinity to oxygen
- positvely charged amino acids
16
Q
2
- HbA
- Four subunits or monomers
two alpha-globin AND two beta-globin = 4 monomers - HbF
HbA2
- Four subunits or monomers
A
page 33
Minor hemoglobins
* what is the most abundant hemoglobin in adults? * define what a tetramer is ? * hemoglobin tetramers are composed of ? * what type of Hbis onlyformed during fetal development * what other type of hemoglobin is found in adults but in lower concetrations thanHbA?
17
Q
2
- Sickle Cell anemia
single nucleotide substitution- recessive
- two MUTANT genes (one form each parent)
BS
Alpha2 BS2
HbS (so sickling can occur)
A
Sickle Cell Anemia HbS
* Hemoglobin S disease is called ? * HbS is caused by how many nucleotide substitutions ? * Sickle cell Anemia is an Autosomal \_\_\_\_\_\_\_\_\_\_disorder what kind of genes are inherited in HbS? The mutant B-globin chain is designated as what ? * the resulting hemoglobin chain composition HbS? * Signs doesnt appear until sufficientHbF isreplaced by
18
Q
Hemoglobin C Disease
like HbS, HbC isa variant that has a single amino acid substitution in which position ? single amino acid substitution happens at the sixth position of which chain ? Alpha or Beta ? * The differnece in single substitution of HbC and HbS * Severity of anemias * HbC and therapy ? what did the book say ?
A
- sixth position
- Beta-globin chain
HbC= Lysine -Glutamate and HbS= Valine - Glutamate - mild chronichemolytic anemia
- doesnt need specific therapies
- Beta-globin chain
19
Q
2
- allosteric inhibition
- hemoglobin will dump off oxygen to that area
- oxygen comes off the hemoglobin
A
- unloading oxygen depends on
- the more H+ there is …., the more what happens
- the more acidic the environment … the more
20
Q
2
Alpha0 or Beta0
Alpha + - or Beta + -
A
Thalassemia
Chain Compositions
in normal HbA alpha and beta chains are produced correctly and are partnered or paired. In Thalassemia its either :
* No Globin chain poduced
or 2. one in which some chains are made BUT at a reduced level
21
Q
- the combination of CO toxicity result from ?
- what kind of treatment can help CO poisoning?
- what type of therapy facilitates the dissociation of CO latched onto the hemoglobin ?
- In addition to O2 and CO2 and CO? what else can be caried by hemoglobin ?
- what does Nitric Oxide do to blood vessels ?
- when NO is released by RBCs what potentially happens ?
A
- tissue hypoxia and CO-mediated damage in the cellular level
100% O2at high pressure (hyperbaric oxygen therapy)- hyperbaric oxygen therapy
- NO (Nitric Oxide)
- dilate (potent vasodilator)
- influences the diameter of blood vessels
22
Q
The effect of cooperativity
“Cooperative Binding”
A
- first subunit binding with oxygen increases 300x greater to the last subunit than the first subunit
- as the first out of four subunit binds onto oxygen the love and attraction to oxygen becomesstronger
- loading and unloading allows hemoglobin to deliver more O2 to tissues in response to relatively small changes to partial pressures
23
Q
2
- bicarbonate
- carbamate
- terminal amino groups of hemoglobin
- T form
- Right shift
A
page 32
CO2 Binding
most of the CO2 produced in metabolism is hydrated andtransported as ? some of the CO2 however are carried as ? CO2's that are carried as carbamate are bound to where ? Binding of CO2stabilizeswhich form ? what direction in the oxygen dissociation curve describes the binding of CO2as in (stabilizing T form) ?
24
Q
- sixth position
- Beta-globin chain
HbC= Lysine -Glutamate and HbS= Valine - Glutamate - mild chronichemolytic anemia
- doesnt need specific therapies
- Beta-globin chain
A
Hemoglobin C Disease
like HbS, HbC isa variant that has a single amino acid substitution in which position ? single amino acid substitution happens at the sixth position of which chain ? Alpha or Beta ? * The differnece in single substitution of HbC and HbS * Severity of anemias * HbC and therapy ? what did the book say ?
25
# 2
* hereditary* imbalance in alpha or beta globin chains* most common single gene-disorder in humansnormal HbA have Alpha2 and Beta2 and are paired partners ( in Thalasemias- either the Alpha or Beta is defective)* Hb concentration in Thal is reduced* can be caused by entire gene deletions or substitutions of one of MANY nucleotides in a DNA
Thalassemias
* cause of thalasemia ?
* thalasemmia is an imbalance in which chains ?
* what type of disorder is Thalassemia ?
* normal HbA have Alpha2 and Beta2 paired-describe the defect in globin chains in Thalassemia ?
* the concentration of what is reduced ?
* Thalassemia is caused by deletions or substitutions in one or MANY what ?
26
CO Binding
Hemoglobin is more attracted to ________ over O2
* what part of the hemoglobin does CO bind tightly ?
* when CO is binded to the iron of Hb what is it called?
* When CO binds to one of the four heme sites what shape or conformation (T/ R) will it form ?
* remind me what the R form is about again?
* The oxygen-dissociation curve shifts (right/left) ?
* in this case ( the affected Hemoglobin) is unable to unload what ?
* Carbon monoxide
* binds tightly but reversibly to IRON (Fe2+)
* carboxyhemoglobin
* forms the R form
* relaxed form (oxygenated) high affinity for O2
* shifts to the left
* oxygen to the tissues
27
Thalassemia
Chain Compositions
in normal HbA alpha and beta chains are produced correctly and are partnered or paired. In Thalassemia its either :
* No Globin chain poduced
or 2. one in which some chains are made BUT at a reduced level
Alpha0 or Beta0
Alpha + - or Beta + -
28
* unloading oxygen depends on
* the more H+ there is there more...
* the more acidic the environment ... the more
* allosteric inhibition
* hemoglobin will dump off oxygen to that area
* oxygen comes off the hemoglobin
29
Sickle Cell Anemia HbS
* Hemoglobin S disease is called ?
* HbS is caused by how many nucleotide substitutions ?
* Sickle cell Anemia is an Autosomal __________disorder
what kind of genes are inherited in HbS?
The mutant B-globin chain is designated as what ?
* the resulting hemoglobin chain composition HbS ?
* Signs doesnt appear until sufficient HbF is replaced by
* Sickle Cell anemia
single nucleotide substitution
* recessive
* two MUTANT genes (one form each parent)
BS
Alpha2 BS2
HbS (so sickling can occur)
30
# 2
* first subunit binding with oxygen increases 300x greater to the last subunit than the first subunit
* as the first out of four subunit binds onto oxygen the love and attraction to oxygen becomes stronger
* loading and unloading allows hemoglobin to deliver more O2 to tissues in response to relatively small changes to partial pressures
The effect of cooperativity
"Cooperative Binding"
