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Flashcards in Hemoglobin and Myoglobin Deck (24):
1

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. 

2

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

3

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

4

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

5

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

6

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

7

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

8

 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

9

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

10

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

11

12

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 

13

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

14

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

15

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

16

2,3-Bisphosphoglycerate 

•Synthesized in ____ from the glycolytic intermediate____

•Highly ___ compound

•Present at approximately the __ ___ of hemoglobin

•In the absence of 2,3-BPG, hemoglobin has a ___ affinity for O2

 

How can we influence the release of O2

Byproduct of glycolytic pathway

Has a lot of – charges

Always present at same [] of Hb

In absence of 23 BPG, Hb will have high affinity for O2

2,3-Bisphosphoglycerate 

•Synthesized in erythrocytes from the glycolytic intermediate 1,3-BPG

•Highly anionic compound

•Present at approximately the same concentration of hemoglobin

•In the absence of 2,3-BPG, hemoglobin has a higher affinity for O2

 

How can we influence the release of O2

Byproduct of glycolytic pathway

Has a lot of – charges

Always present at same [] of Hb

In absence of 23 BPG, Hb will have high affinity for O2

17

2,3-BPG Stabilizes the ___ Structure of Hemoglobin

•A ___ molecule of 2,3-BPG occupies the ___ of the hemoglobin tetramer

•Interacts with ___ charged groups of the __ subunits

•Binds to the pocket in the ___ state

•Binds preferably to ____ hemoglobin, stabilizing it

____ the affinity for O2

•T to R state results in the ___ ____

•Expelling ___

 

Basically it stabilizes the T state

Molecules that occupy center of Hb are all positively charged

BPG is a very negative molecule

Leads to electrostatic interactions

Stabilizes the structure and leave it in T form

Now Hb is unable to bind O2

But it will release O2 better

In order to shift back to R, 23BGP has to dissociate

2,3-BPG Stabilizes the T Structure of Hemoglobin

•A single molecule of 2,3-BPG occupies the center of the hemoglobin tetramer

•Interacts with positively charged groups of the b subunits

•Binds to the pocket in the T state

•Binds preferably to deoxyhemoglobin, stabilizing it

•Decreases the affinity for O2

•T to R state results in the pocket collapsing

•Expelling 2,3-BPG

 

Basically it stabilizes the T state

Molecules that occupy center of Hb are all positively charged

BPG is a very negative molecule

Leads to electrostatic interactions

Stabilizes the structure and leave it in T form

Now Hb is unable to bind O2

But it will release O2 better

In order to shift back to R, 23BGP has to dissociate

18

Relative Affinities of Different Hemoglobins for Oxygen (Adult vs. Fetal)

•HbF tetramer consists of two ___ subunits instead of two ___ subunits found in HbA

•____% of the amino acid sequence in the g subunit is identical to the b subunit

•Substitution of  a ____ for ____ in the ___ subunit results in loss of ___ positive charges in the 2,3-BGP ___

___ does not bind 2,3-BPG as well as ____ hemoglobin

•Fetal red blood cells have a ___ oxygen affinity than that of maternal red blood cells

•Difference in oxygen affinity allows oxygen to be effectively transferred from maternal to fetal red cells

 

Where is 23 BPG important?

High altitude. Lower ___ ___

Those indiv have __ ___ thus more  Hb and more 23 BPG

Their Hb has ___ capacity to bind O2

But they compensate by having a high number of RBC

Still able to carry enough O2 for physiological purposes but not carrying same capacity of O2 as people at lower elevations

23BPG is also important in fetal and maternal blood.

A serine residuce substitutes His 143

His 143 is in that central cavity where 23BPG interacts

If you lose a + charge, interaction by 23BPG will be less

Fetal hb doesn’t bind to 23BPG as well as maternal Hb

Fetal blood cells have high Oxygen affinity compared to mom

So O2 will move from mom to baby

That ensures that the fetus gets nutrients from the mom

Relative Affinities of Different Hemoglobins for Oxygen (Adult vs. Fetal)

•HbF tetramer consists of two g subunits instead of two b subunits found in HbA

•72% of the amino acid sequence in the g subunit is identical to the b subunit

•Substitution of  a serine for His143 in the g subunit results in loss of 2 positive charges in the 2,3-BGP pocket

•HbF does not bind 2,3-BPG as well as maternal hemoglobin

•Fetal red blood cells have a higher oxygen affinity than that of maternal red blood cells

•Difference in oxygen affinity allows oxygen to be effectively transferred from maternal to fetal red cells

 

Where is 23 BPG important?

High altitude. Lower O2 content

Those indiv have more RBC, thus more  Hb and more 23 BPG

Their Hb has less capacity to bind O2

But they compensate by having a high number of RBC

Still able to carry enough O2 for physiological purposes but not carrying same capacity of O2 as people at lower elevations

23BPG is also important in fetal and maternal blood.

A serine residuce substitutes His 143

His 143 is in that central cavity where 23BPG interacts

If you lose a + charge, interaction by 23BPG will be less

Fetal hb doesn’t bind to 23BPG as well as maternal Hb

Fetal blood cells have high Oxygen affinity compared to mom

So O2 will move from mom to baby

That ensures that the fetus gets nutrients from the mom

19

Transportation of CO2 & Protons by Hemoglobin

•CO2  produced during respiration is converted to ___ ___ by ___ ___e in the ____

•Carbonic acid is ___ acid that dissociates into protons and ___

•In the peripherial tissue,  ~___ proton binds to ___releasing __ ___molecules (Hb act as a buffer)

•In the lung, bicarbonate ____ with ___ released by  __ forming __ __

•Carbonic acid is converted back to___ and ___

•Enables Hb to bind to ___ in the lungs

 

We respire and produce CO2.

CO2 will be converted to Carbonic acid.

Converted by carbonic anhydrase

Takes place in RBC

Weak acid

Dissociate into protons and bicarb

Protons influence affinity for O2

Proton binds, it ___ O2

As bicarb and protons move they reenter the lungs/.

There they combine to form carbonic acid

Carbonic Acid will dissociate back into CO2 and water

Presence of O2 enables whether O2 will be released at the tissues

More respire. More CO2 produced. More H+. More re;lease of O2

Transportation of CO2 & Protons by Hemoglobin

•CO2  produced during respiration is converted to carbonic acid by carbonic anhydrase in the RBCs

•Carbonic acid is weak acid that dissociates into protons and bicarbonate

•In the peripherial tissue,  ~ one proton binds to Hb releasing two O2 molecules (Hb act as a buffer)

•In the lung, bicarbonate associates with protons released by Hb forming carbonic acid

•Carbonic acid is converted back to CO2 and H2O

•Enables Hb to bind to O2 in the lungs

 

We respire and produce CO2.

CO2 will be converted to Carbonic acid.

Converted by carbonic anhydrase

Takes place in RBC

Weak acid

Dissociate into protons and bicarb

Protons influence affinity for O2

Proton binds, it releases O2

As bicarb and protons move they reenter the lungs/.

There they combine to form carbonic acid

Carbonic Acid will dissociate back into CO2 and water

Presence of O2 enables whether O2 will be released at the tissues

More respire. More CO2 produced. More H+. More re;lease of O2

20

Transportation of CO2 & Protons by Hemoglobin

•Small proportion of ___ reacts with terminal ___ groups forming ____ (CO2 mostly carried as bicarbonate)

•Results in ____ charged termini at the ___  of the ab dimers

•Forms___ ___s, stabilizing the ___hemoglobin structure (favors ___ state)

Also a Small amt of CO2 can bind to Hb

Certain amino groups will form these carbamates by binding to CO2

Termini of these proteins are negatively charged

Carboxyllic groups bound at N termmini are neg charged

That destabilizes structure of Hb and favors T state

Release more O2

If we Favor the R state: ensures more binding of O2

Transportation of CO2 & Protons by Hemoglobin

•Small proportion of CO2 reacts with terminal amino groups forming carbamates (CO2 mostly carried as bicarbonate)

•Results in negatively charged termini at the interface of the ab dimers

•Forms salt bridges, stabilizing the deoxyhemoglobin structure (favors T state)

Also a Small amt of CO2 can bind to Hb

Certain amino groups will form these carbamates by binding to CO2

Termini of these proteins are negatively charged

Carboxyllic groups bound at N termmini are neg charged

That destabilizes structure of Hb and favors T state

Release more O2

If we Favor the R state: ensures more binding of O2

21

Bohr Effect

•The regulation of oxygen binding by __ __s and __ ___

•Salt bridge formation occurs due to the ___n of certain residues in the a and b chains at ___ pH (Ex:- b His146 and Asp94)

•Results in stabilization of the ___ state

•The lowering of pH results further in the____ of O2

Effect of pH on O2 binding has been well studied

As pH decreases more O2 will be released

This is bc you are stabilizing the T state

Bohr Effect

•The regulation of oxygen binding by hydrogen ions and carbon dioxide

•Salt bridge formation occurs due to the protonation of certain residues in the a and b chains at low pH (Ex:- b His146 and Asp94)

•Results in stabilization of the deoxy state

•The lowering of pH results further in the release of O2

Effect of pH on O2 binding has been well studied

As pH decreases more O2 will be released

This is bc you are stabilizing the T state

22

Sickle Cell Anemia 

•Invariant residue

–residue that is always ___

–these residues are essential to the ___ /___ of the protein

•Sickle cell hemoglobin (HbS) contains a __ rather than a ___ at the 6th position of the b subunit

•Valine residue fits into a ___ pocket of another ___ chain resulting in polymerization of Hb forming ___ (occurs only in the ___hemoglobin S)

•___erythrocytes into sickle shaped cells which results in__ __ ___

Val is more hydrophobic

Glu is more polar

Change environment of protein

As a result there is this Polymerization

B chains join together to form this structure

As you build long structure of Beta units bc of this mutation it results in forming fibers

Hb occupies RBC so it will distort the structure of the RBC

Sickle shape

It will pack in the blood vessels

This results in clotting or blockages

Single copy of this mutation offers an advantage bc of malaria

Parasite cant infect sickle shaped cells

2 mutations is fatal

Sickle Cell Anemia 

•Invariant residue

–residue that is always conserved

–these residues are essential to the structure/function of the protein

•Sickle cell hemoglobin (HbS) contains a valine rather than a glutamate at the 6th position of the b subunit

•Valine residue fits into a hydrophobic pocket of another b chain resulting in polymerization of Hb forming fibers (occurs only in the deoxyhemoglobin S)

•Distorts erythrocytes into sickle shaped cells which results in blood flow blockage

Val is more hydrophobic

Glu is more polar

Change environment of protein

As a result there is this Polymerization

B chains join together to form this structure

As you build long structure of Beta units bc of this mutation it results in forming fibers

Hb occupies RBC so it will distort the structure of the RBC

Sickle shape

It will pack in the blood vessels

This results in clotting or blockages

Single copy of this mutation offers an advantage bc of malaria

Parasite cant infect sickle shaped cells

2 mutations is fatal

23

Glycated Hemoglobin (HbA1c)

•Blood glucose enters the erythrocytes, it ____ the ε-amino group of ___ residues and the____ terminals of hemoglobin.

•The fraction of hemoglobin glycated, normally about ___ %, is proportionate to__ __ ___

•Since the half-life of an erythrocyte is typically ___ days, the level of glycated hemoglobin (HbA1c) reflects the ___ blood glucose concentration over the preceding __ to __ weeks.

•Measurement of HbA1c therefore provides valuable information for management of diabetes mellitus.

 

Very good index to see if you are diabetic or not

Better index then testing your blood glucose levels

Glucose is added to those residues

Halflife of RBC is generally bw 60-120 days

So the levels of bound glucose are more constant thruout that period

Fasting blood glucose levels fluctuate bw day and night

Diabetic: __ and above

___ you are on the borderline. Maybe prediabetic

Under __  is great!

 

Glycated Hemoglobin (HbA1c)

 

•Blood glucose enters the erythrocytes, it glycates the ε-amino group of lysyl residues and the amino terminals of hemoglobin.

•The fraction of hemoglobin glycated, normally about 5%, is proportionate to blood glucose concentration.

•Since the half-life of an erythrocyte is typically 60 days, the level of glycated hemoglobin (HbA1c) reflects the mean blood glucose concentration over the preceding 6 to 8 weeks.

•Measurement of HbA1c therefore provides valuable information for management of diabetes mellitus.

 

Very good index to see if you are diabetic or not

Better index then testing your blood glucose levels

Glucose is added to those residues

Halflife of RBC is generally bw 60-120 days

So the levels of bound glucose are more constant thruout that period

Fasting blood glucose levels fluctuate bw day and night

Diabetic: 7 and above

6.5 you are on the borderline. Maybe prediabetic

Under 5.5 is great!

24

•Myoglobin is a monomeric heme containing protein that facilitates O2 transport in the muscle

•Hemoglobin is a tetrameric heme protein that has different confirmations (R and T) in its oxy and deoxy states

•O2 binds to hemoglobin in a cooperative manner

•Through the Bohr effect, protons and CO2 promote O2 ___ from Hb

•2,3-BPG ___ the affinity of Hb for O2

•Formation of rigid fibers of HbS is an example where hemoglobin variants reveal protein structure function relationships