Hemoglobin and Myoglobin Flashcards
Protein Structure
1: number and seq of aa
2: Unique elements define structure. Alpha helices, B sheets, Then you get turns and loops
3: This is the favored structure. Has leas amount of energy. 3D structure
4: one or more tertiary structures come together to form a protein. Units could be homomeric or heteromeric.
1: number and seq of aa
2: Unique elements define structure. Alpha helices, B sheets, Then you get turns and loops
3: This is the favored structure. Has leas amount of energy. 3D structure
4: one or more tertiary structures come together to form a protein. Units could be homomeric or heteromeric.
Functions of Heme Proteins Hemoglobin and Myoglobin
- Proteins, hemoglobin and myoglobin illustrate the relationship between structure and function
- Maintain a supply of oxygen essential for ___ ___
- Myoglobin, a monomeric protein found in__ ___
–facilitate O2 ___ in the ___ (oxygen storage in ___ mammals – seals and whales)
•Hemoglobin, a ___ protein of ___
–transports O2 to the___ and returns ___ and ___ to the ___
•
Have iron
Important for: Transport and store O2
Supply O2 for oxidative rxns
Myoglobin just one tertiary structure (monomer)
More important for aquatic mammals. Dive down into the ocean and need O2. Their muscles store a lot of myoglobin
We don’t need it as much bc our environ has High O2 content
Functions of Heme Proteins Hemoglobin and Myoglobin
- Proteins, hemoglobin and myoglobin illustrate the relationship between structure and function
- Maintain a supply of oxygen essential for oxidative metabolism
- Myoglobin, a monomeric protein found in skeletal muscles
–facilitate O2 transport in the muscle (oxygen storage in aquatic mammals – seals and whales)
•Hemoglobin, a tetrameric protein of erythrocytes
–transports O2 to the tissues and returns CO2 and protons to the lungs
•
Have iron
Important for: Transport and store O2
Supply O2 for oxidative rxns
Myoglobin just one tertiary structure (monomer)
More important for aquatic mammals. Dive down into the ocean and need O2. Their muscles store a lot of myoglobin
We don’t need it as much bc our environ has High O2 content
Myoglobin Structure
- ___ protein
- Consists of 153 amino acid residue
- Mainly comprised of __ right-handed a-helices
- Helices are denoted ___
- Heme lies in a crevice (____ pocket) between helices __ and __
Myoglobin Structure
- Globular protein
- Consists of 153 amino acid residue
- Mainly comprised of 8 right-handed a-helices
- Helices are denoted A-H
- Heme lies in a crevice (hydrophobic pocket) between helices E and F
Heme
- ___ derivative
- ____ic ring structure
- Consists of
–4 ___ groups linked by ___ ___
–Central Fe(__) atom are coordinated to 4 porphyrin___n atoms
–Forms two additional bonds ___ and ___ the heme plane (5th and 6th coordination sites)
Iron is always in the 2nd oxidative state…Ferrous ion (Fe2+)
Ferric: (Fe3+) Never see it like this is Hb
Heme
- Porphyrin derivative
- Heterocyclic ring structure
- Consists of
–4 pyrrole groups linked by methene bridges
–Central Fe(II) atom are coordinated to 4 porphyrin Nitrogen atoms
–Forms two additional bonds above and below the heme plane (5th and 6th coordination sites)
Iron is always in the 2nd oxidative state…Ferrous ion (Fe2+)
Ferric: (Fe3+) Never see it like this is Hb
Porphyrin Ring of Myoglobin/Hemoglobin
- Nitrogen atom of the __th Histidine residue of helix ___ coordinates with Fe (II)
- Valine ___ (helix E, 11th residue) and Phenylalanine ___ (between helix C & D) hold the heme in place by ___ ___
•
•Histidine E7 is ___ to Histidine F8
•
5th coordination position: Nitrogen Atom of 8th histidine residue coordinates with Fe II
Important for stabilizing the ferrous ring
Also have Val E11 and phenylalanine bw helix C and D. They also further stabilize the structure
They hold the ion in place
When Iron isnt attached to O2 its below the porphyrin plane
When O2 binds it moves up into the plane of porph ring
Also right above the porphyrin ring is another His res which can have some interactions
Important for it to be right above the heme structure bc
CO can bind much better than O2 so it has a higher affinity to Hb than O2
When CO binds, its in a linear formation
O2 binds at an angle of 120
Histidine causes steric hinderence and doesn’t allow CO to bind
Porphyrin Ring of Myoglobin/Hemoglobin
- Nitrogen atom of the 8th Histidine residue of helix F coordinates with Fe (II)
- Valine E11 (helix E, 11th residue) and Phenylalanine CD1 (between helix C & D) hold the heme in place by hydrophobic interactions
•
•Histidine E7 is opposite to Histidine F8
•
5th coordination position: Nitrogen Atom of 8th histidine residue coordinates with Fe II
Important for stabilizing the ferrous ring
Also have Val E11 and phenylalanine bw helix C and D. They also further stabilize the structure
They hold the ion in place
When Iron isnt attached to O2 its below the porphyrin plane
When O2 binds it moves up into the plane of porph ring
Also right above the porphyrin ring is another His res which can have some interactions
Important for it to be right above the heme structure bc
CO can bind much better than O2 so it has a higher affinity to Hb than O2
When CO binds, its in a linear formation
O2 binds at an angle of 120
Histidine causes steric hinderence and doesn’t allow CO to bind
Oxygenation of Heme Group
- Un-oxygenated Fe(II) lies____ the plane of the porphyrin ring
- When O2 occupies the___ position Fe(II) moves ___ the ___ of the ring
- Un-oxygenated Fe(II) lies outside the plane of the porphyrin ring
- When O2 occupies the sixth position Fe(II) moves within the plane of the ring
Comparison Between Hemoglobin and Myoglobin Structures
•Only ___% of the residues in myoglobin are identical to the subunits (a and b) in hemoglobin
____ structure is very similar between the polypeptides
•Absence of helix___ in the ___ subunits of hemoglobin
•
Hb is made of tertiary structure that are similar to the Mb
Indiv aa are not very similar though
Alpha of Hb: A to F but not D helix
Beta has all A-F
Comparison Between Hemoglobin and Myoglobin Structures
- Only 18% of the residues in myoglobin are identical to the subunits (a and b) in hemoglobin
- Tertiary structure is very similar between the polypeptides
- Absence of helix D in the a subunits of hemoglobin
•
Hb is made of tertiary structure that are similar to the Mb
Indiv aa are not very similar though
Alpha of Hb: A to F but not D helix
Beta has all A-F
Oxygen-binding Curves of Myoglobin & Hemoglobin
- O2 binding curve for myoglobin is a ___ ___
- Releases ___ fraction of O2 over the physiological range of pO2 (lung vs tissues)
- O2 binding curve for hemoglobin is ___
- Releases ___ fraction of O2 over the physiological range of pO2 (lung vs tissues)
•
•
% saturation: how many spots are occupied by O2
Mb: Typical rectangular hyperbola
If you take the lungs, they have high content of O2 so PP for O2 there is about___ mm Hg
In the tissues the PP of O2 is about ___
Going from lungs to tissues how much O2 is given off by myoglobin?
It will only release 20%,
Its great at capturing O2 though
At low PP of O2 you can saturate it very quickly
Hb: sigmoidal curve
When Hb moves from lungs to the tissues, you are releasing about 60-70%
Good at releasing O2
Gets oxygenated in the lungs and then moves to the peripheral tissues and it gives you a large conc of O2 so the tissues can respire
Oxygen-binding Curves of Myoglobin & Hemoglobin
- O2 binding curve for myoglobin is a rectangular hyperbola
- Releases small fraction of O2 over the physiological range of pO2 (lung vs tissues)
- O2 binding curve for hemoglobin is sigmoidal
- Releases large fraction of O2 over the physiological range of pO2 (lung vs tissues)
•
•
% saturation: how many spots are occupied by O2
Mb: Typical rectangular hyperbola
If you take the lungs, they have high content of O2 so PP for O2 there is about 100 mm Hg
In the tissues the PP of O2 is about 20
Going from lungs to tissues how much O2 is given off by myoglobin?
It will only release 20%,
Its great at capturing O2 though
At low PP of O2 you can saturate it very quickly
Hb: sigmoidal curve
When Hb moves from lungs to the tissues, you are releasing about 60-70%
Good at releasing O2
Gets oxygenated in the lungs and then moves to the peripheral tissues and it gives you a large conc of O2 so the tissues can respire
Hemoglobin Structure
- ___mer
- Two different polypeptide subunits
–___ and___ (HbA; normal adult hemoglobin)
–__ and ___(HbF; fetal hemoglobin)
•Similar tertiary structure to myoglobin
•
Why does it have this capacity to release large fraction ? Lets look at the structure
Two forms of Hb
Adult and Fetal
Hemoglobin Structure
- Tetramer
- Two different polypeptide subunits
–a2b2 (HbA; normal adult hemoglobin)
–a2g2 (HbF; fetal hemoglobin)
•Similar tertiary structure to myoglobin
•
Why does it have this capacity to release large fraction ? Lets look at the structure
Two forms of Hb
Adult and Fetal
The Allosteric Properties of Hemoglobin
•Hb has only two ___ conformation states
– T (t__) state (____) and R (___) state (___)
•___ binding causes the T state to shift to the R state, which has ___ affinity for O2
•
Its an Allosteric protein
Two conformations
T: Tense. ___ affinity for O2
R: Relaxed: __ affinity for O2
Based on conformations the Hb has different affinity to O2
The Allosteric Properties of Hemoglobin
•Hb has only two stable conformation states
– T (taut) state (deoxyHb) and R (relaxed) state (oxyHb)
•Oxygen binding causes the T state to shift to the R state, which has greater affinity for O2
•
Its an Allosteric protein
Two conformations
T: Tense. Low affinity for O2
R: Relaxed: High affinity for O2
Based on conformations the Hb has different affinity to O2
Transition from T to R State
•One pair of ab subunits shifts with respect to the other by a rotation of ___ degrees
___ between the α1β1 and α2β2 ___ is most affected by this transition
Transformation occurs bc there is a shift at the interface bw the 2 subunits.
15 degree transition
An alphaBeta subuit will shift in resepect to the other alphabeta subunit
Transition from T to R State
- One pair of ab subunits shifts with respect to the other by a rotation of 15 degrees
- Interface between the α1β1 and α2β2 dimers is most affected by this transition
Transformation occurs bc there is a shift at the interface bw the 2 subunits.
15 degree transition
An alphaBeta subuit will shift in resepect to the other alphabeta subunit
Structural Changes from T to R Shift
- The T to R shift is triggered by ___ ___ to the heme, which pulls the___ (II) atom into the heme plane
- This movement is transmitted to the ___ helix through ___ ___
- Conformational changes in ___ subunit are transmitted across the α1-β2 and α2-β1 ____
- As a result, conformational shift occurs in___ ___
Binding of O2 to heme is what triggers change
Pulls Fe into the plane of heme
heme is attached to His.
His below the plane is part of F helix
Pull up his
Pull up F helix
Causes conf change in that subunit and as a result have a 15 degree shift at the interface
Overal confermation change bc of binding of O2 to one subunit
Structural Changes from T to R Shift
- The T to R shift is triggered by O2 binding to the heme, which pulls the Fe(II) atom into the heme plane
- This movement is transmitted to the F helix through His F8
- Conformational changes in one subunit are transmitted across the α1-β2 and α2-β1 interfaces
- As a result, conformational shift occurs in all subunits
Binding of O2 to heme is what triggers change
Pulls Fe into the plane of heme
heme is attached to His.
His below the plane is part of F helix
Pull up his
Pull up F helix
Causes conf change in that subunit and as a result have a 15 degree shift at the interface
Overal confermation change bc of binding of O2 to one subunit
Transition from T to R State
Two modes for cooperativity have been proposed
- ___ model
- the ____ model
Two theories
Patterns of shift from T to R
Symmet: Once molecule binds, all Ts are converted to Rs
Seque: Step wise. First O2 binds to first subunit.
For Hb, there is no consensus on which it is…its a combo of both
Hybrid version
Transition from T to R State
Two modes for cooperativity have been proposed
- Symmetry model
- the Sequential model
Two theories
Patterns of shift from T to R
Symmet: Once molecule binds, all Ts are converted to Rs
Seque: Step wise. First O2 binds to first subunit.
For Hb, there is no consensus on which it is…its a combo of both
Hybrid version
Cooperative Binding of Oxygen
When O2 binding is ____ (____curve)
- In the lungs, pO2 is ~100 torr, whereas the tissues, pO2 is 20 torr
- In the lung, Y=__%
- Moves to the tissues Y=~ ___%
- ___% of the binding sites contribute to O2 transport
In the absence of cooperative binding (___c curve)
- In the lung only Y=___% and at the tissue it is only Y=__%
- ONLY ___% contributes to O2 transport
O2 Allosteric molecule, cooperative binding
When Hb moves from lungs to peripheral tissues it gives up about 66 %
If it was not cooperative, it will only release 38% of O2
Ability to bind in cooperative manner enhances release of O2 to tissues
Cooperative Binding of Oxygen
When O2 binding is cooperative (sigmoid curve)
- In the lungs, pO2 is ~100 torr, whereas the tissues, pO2 is 20 torr
- In the lung, Y=98%
- Moves to the tissues Y=~ 32%
- 66% of the binding sites contribute to O2 transport
In the absence of cooperative binding (hyperbolic curve)
- In the lung only Y=63% and at the tissue it is only Y=25%
- ONLY 38% contributes to O2 transport
O2 Allosteric molecule, cooperative binding
When Hb moves from lungs to peripheral tissues it gives up about 66 %
If it was not cooperative, it will only release 38% of O2
Ability to bind in cooperative manner enhances release of O2 to tissues
