Study the effect of changes in BPG concentration at one particular oxygen tension
before changing the oxygen tension.
For example, study the effect of BPG at concentrations of 5mM and 10mM at a oxygen partial pressure of 100mmHg.
Once you have grasped this concept, change the oxygen tension and continue the study as before.
text1
text2
text3
text4
text5
text6
text7
text8
text9
text4
text1
text2
text3
text5
text6
text7
text8
text9
text7
text4
text1
text2
text3
text5
text6
text8
text9
text2
text1
text3
text4
text5
text6
text7
text8
text9
text5
text4
text1
text2
text3
text6
text7
text8
text9
text8
text4
text1
text2
text3
text6
text7
text9
text3
text2
text1
text4
text5
text6
text7
text8
text9
text6
text5
text4
text3
text2
text1
text7
text8
text9
text9
text5
text4
text3
text2
text1
text7
text8
leavePage
barchart
barchart
text1
text2
text3
text4
text5
text6
text7
text8
text9
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
:PHYSSIZE
NextPage
default
buttonUp
buttonUp
default
backPage
Previous
default
buttonUp
buttonUp
Previous
default
The model shows the four subunit structure of haemoglobin with the haem groups (gold) and iron atom (silver). Try videos on next page
4drop
"HM3"
"HM2"
"HM1"
"HM11"
"O21"
3880, 2660
3880, 2660, 4300, 2975
"O22"
4690, 2660
4690, 2660, 5125, 2975
3880, 2660
4690, 2660
3940, 2660, 4250, 2975
3880, 2660, 4300, 2975
3940, 2660, 4250, 2975
nthe
3170, 2660
3170, 2660, 3590, 2975
ZhorizPos
3170
-370
H-100
., 2660
3880, 2660
3880, 2660, 4300, 2975
4750, 2660, 5075, 2975
4690, 2660, 5125, 2975
4750, 2660, 5075, 2975
5580, 2660
5580, 2660, 6015, 2975
5580
8980
, 2660
4690, 2660
4690, 2660, 5125, 2975
enterPage
enterPage
333333
horizPos:by
horizPos:to
horizPos
"quest5"
"quest6"
leavePage
leavePage
quest5
quest6
6. How many types of subunit does Haemoglobin contain?::::::::::::::::::
6eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee
5. Is Haemoglobin::::::::::::::::::::::
A monomer
A dimer
A trimer
A tetramer
A pentamer
quest5
quest6
NextPage
4questscore5
4questscore6
B"5a"
B"5b"
B"5c"
B"5d"
B"5e"
B"6a"
B"6b"
B"6c"
B"6d"
B"6e"
default
buttonUp
buttonUp
default
questscore6
questscore5
"quest7"
"quest8"
leavePage
leavePage
quest7
quest8
7. What atom is found in the centre of a Haem molecule?
Calcium
Sodium
Sulphur
Phosphorus
8. Which subunit contact is altered in the R-T state transition?
a1/b1
a2/b2
a1/b2
a2/b1
a1/a2
quest7
quest8
Basic
NextPage
4questscore9
4questscore10
B"9a"
B"9b"
B"9c"
B"9d"
B"9e"
B"10a"
B"10b"
B"10c"
B"10d"
B"10e"
default
buttonUp
buttonUp
default
questscore10
questscore9
"quest9"
"quest10"
leavePage
leavePage
quest9
quest10
9. How many electrostatic interactions stabilize the T state?
10. The shape of the haemoglobin-oxygen dissociation curve is:::G
Hyperbolic
Linear
Convex
Sigmoidal
Concave
quest9
quest10
Basic
NextPage
4questscore11
4questscore12
B"11a"
B"11b"
H1.25
B"11c"
H1.25
B"11d"
H1.25
B"11e"
H1.25
B"12a"
B"12b"
B"12c"
B"12d"
B"12e"
default
buttonUp
buttonUp
default
questscore12
questscore11
"quest11"
"quest12"
leavePage
leavePage
quest11
quest12
11.Which statements are correct concerning oxygen binding to haemoglobin?
The binding of the 1st oxygen is the least difficult
The binding of the 2nd oxygen is easier than the 1st
The binding of the 3rd oxygen is easier than the 2nd
The binding of the 4th oxygen is easier than the 3rd
The binding of the 4th oxygen is easier than the second
12. Which statements about the T and R states of haemoglobin are true?
Deoxyhaemoglobin is in the R state
Oxyhaemoglobin is in the R state
R stands for the 'ready' state
T stands for the 'tense' state
Oxygen binding promotes conversion to the T stateggggggggg
quest11
quest12
Basic
"quest13"
"quest14"
leavePage
leavePage
quest13
quest14
14. What effect does BPG have on Haemoglobin?:::::::::::::::::::::::
Increases the affinity for oxygen
Decreases the affinity for oxygen
High levels of BPG increase oxygen delivery
Stabilizes the T state
Stabilizes the R state
quest13
quest14
13. Does BPG interact with::::::::::
Both the T and R states of haemoglobin
Haemoglobin in the T state
Haemoglobin in the R state
Haemoglobin at a ratio of one BPG/molecule
Haemoglobin at a ratio of one BPG/subunittyyyany way any wayn any way
NextPage
4questscore13
4questscore14
B"13a"
B"13b"
B"13c"
B"13d"
B"13e"
B"14a"
B"14b"
B"14c"
B"14d"
B"14e"
default
buttonUp
buttonUp
default
questscore14
questscore13
4questscore19
4questscore20
B"19a"
B"19b"
B"19c"
B"19d"
B"19e"
B"20a"
B"20b"
B"20c"
B"20d"
B"20e"
4questscore18
4questscore17
4questscore16
4questscore15
4questscore14
4questscore13
4questscore12
4questscore11
4questscore10
4questscore9
4questscore8
4questscore7
4questscore6
4questscore5
4questscore4
4questscore3
--System count
questscores
--Obtain dialog box showing total no
points
"You scored" &&
out
a possible 100"
--shows nextpage
B- avoids
Bbeing pressed without
--obtaining
B"NextPage"
default
buttonUp
buttonUp
You scored
points out of a possible 100
NextPage
default
count
questscore1
questscore2
questscore3
questscore4
questscore5
questscore6
questscore7
questscore8
questscore9
questscore10
questscore11
questscore12
questscore13
questscore14
questscore15
questscore16
questscore17
questscore18
questscore20
questscore19
Basic
NextPage
4questscore17
4questscore18
B"17a"
H1.25
B"17b"
B"17c"
H1.25
B"17d"
H1.25
B"17e"
H1.25
B"18a"
B"18b"
B"18c"
B"18d"
B"18e"
default
buttonUp
buttonUp
default
questscore18
questscore17
"quest17"
"quest18"
leavePage
leavePage
quest17
quest18
quest17
quest18
17. Which of the following happens in actively working tissues?HH
Carbon dioxide reacts with water
The pH increases
The hydrogen ion concentration increases
The affinity of haemoglobin for oxygen is decreased
Hydrogen ions combine with haemoglobin
18. What effect does a lower pH value(e.g pH 7.2) have on haemoglobin?::::::::
Shifts the T-R equilibrium in favour of the T state
Shifts the T-R equilibrium in favour of the R state
Causes protonation of a histidine residue
Causes deprotonation of a histidine residue
Decreases the amount of oxygen unloaded in the tissues
Basic
B"NextPage"
"quest19"
"quest20"
enterPage
leavePage
enterPage
NextPage
leavePage
quest19
quest20
NextPage
4questscore19
4questscore20
buttonUp
buttonUp
questscore20
questscore19
quest19
quest20
20. What effect does carbon dioxide have on Haemoglobin?::::::::is ::
19. In which form is carbon dioxide transported by haemoglobin?::::::::::::::::
As bicarbonate
As carbon dioxide
As carbon monoxide
As carbamate
Is not transported by haemoglobinn
Score
Press the 'Score' button after finshing the questions to obtain your final score.
No effect
Increases the affinity for oxygen
Decreases the affinity for oxygen
Stabilizes the T state
Stabilizes the R state
B"NextPage"
4questscore20
4questscore19
4questscore18
4questscore17
4questscore16
4questscore15
4questscore14
4questscore13
4questscore12
4questscore11
4questscore10
4questscore9
4questscore8
4questscore7
4questscore6
4questscore5
4questscore4
4questscore3
4count
-- If the
a question
< 5, i.e
got something wrong,
-- answer
that
shown.
"answer1"
"answer2"
"answer3"
"answer4"
"answer5"
"answer6"
"answer7"
"answer8"
"answer9"
"answer10"
"answer11"
"answer12"
"answer13"
"answer14"
"answer15"
"answer16"
"answer17"
"answer18"
"answer19"
"answer20"
enterPage
leavePage
enterPage
NextPage
answer1
answer1
answer2
answer2
answer3
answer3
answer4
answer4
answer5
answer5
answer6
answer6
answer7
answer7
answer8
answer8
answer9
answer9
answer10
answer10
answer11
answer11
answer12
answer12
answer13
answer13
answer14
answer14
answer15
answer15
answer16
answer16
answer17
answer17
answer18
answer18
answer19
answer19
answer20
answer20
NextPage
count
questscore1
questscore2
questscore3
questscore4
questscore5
questscore6
questscore7
questscore8
questscore9
questscore10
questscore11
questscore12
questscore13
questscore14
questscore15
questscore16
questscore17
questscore18
questscore19
questscore20
leavePage
answer1
answer2
answer3
answer4
answer5
answer6
answer7
answer8
answer9
answer10
answer11
answer12
answer13
answer14
answer15
answer16
answer17
answer18
answer19
answer20
count
questscore1
questscore2
questscore3
questscore4
questscore5
questscore6
questscore7
questscore8
questscore9
questscore10
questscore11
questscore12
questscore13
questscore14
questscore15
questscore16
questscore17
questscore18
questscore19
questscore20
Basic
B3<3<3
.b0:1
answer1
"answer1"
buttonUp
buttonUp
answer1
Question 1:
A single red blood cell is capable of carrying 200 million molecules of oxygen. and lactose transacetylase - i.e those that control the entry and metabolism of lactose.
"answer1"
buttonUp
buttonUp
answer1
answer20
"answer20"
buttonUp
buttonUp
answer20
Question 20:
Carbon dioxide decreases the affinity of haemoglobin for oxygen by stabilizing the T state.
ese symmetrical sites are involved in the binding of the repressor and CAP-cAMP complex to the repressor site and CAP site respectively.to the DNA.
answer19
"answer19"
buttonUp
buttonUp
answer19
Question 19:
Carbon dioxide combines with unprotonated a-amino groups in both subunits of haemoglobin as a carbamate.h subunit of the CAP. inding of the appropriate molecule to the DNA strand.
answer18
"answer18"
buttonUp
buttonUp
answer18
Question 18:
Hydrogen ions promote the R to T transition by protonation of Histidine 146 in the b globin. This results in increased oxygen delivery to working tissues.
rator. the DNA strand.
answer17
"answer17"
buttonUp
buttonUp
answer17
Question 17:
In actively working tissues carbon dioxide forms carbonic acid in water and therefore the pH drops and the hydrogen ion concentration rises. The affinity of haemoglobin for oxygen is reduced as hydrogen ions combine with haemoglobin promoting the R to T transition.
answer16
"answer16"
buttonUp
buttonUp
answer16
Question 16:
Histidine 146 binds a hydrogen ion in the T to R transition and is thus involved in the Bohr effect.nd galactose. Both these molecules can be used for energy and as a carbon source.
answer15
"answer15"
buttonUp
buttonUp
answer15
Question 15:
At 4500m less oxygen is taken up by haemoglobin in the lungs and the BPG concentration in the red cell increases. This leads to a decrease in the affinity of haemoglobin for oxygen and the net effect is that oxygen delivery remains the same.
answer14
"answer14"
buttonUp
buttonUp
answer14
Question 14:
BPG decreases the affinity of haemoglobin for oxygen, stabilizing the T state. High levels of BPG lead to enhanced ability to deliver oxygen to working tissues.d as a carbon source.
answer13
"answer13"
buttonUp
buttonUp
answer13
Question 13:
BPG binds to the central cavity in the T state of haemoglobin and only one molecule binds to each haemoglobin molecule........None of the others can directly induce transcription.
answer12
"answer12"
buttonUp
buttonUp
answer12
Question 12:
Deoxyhaemoglobin is usually in the T state with oxyhaemoglobin in the R state.
R stands for Relaxed and T stands for tense. Oxygen binding promotes the T to R transition.
ion.
answer11
"answer11"
buttonUp
buttonUp
answer11
Question 11:
The binding of the first oxygen to haemoglobin is the most difficult and the binding of subsequent oxygens gets progressively easier.i.e. Oxygen binding to haemoglobin is cooperative.
answer10
"answer10"
buttonUp
buttonUp
answer10
Question 10:
The slope of the haemoglobin-oxygen dissociation curve is sigmoidal....these conditions the CAP-cAMP complex is formed. The binding of this complex to the CAP site increases transcription by interacting with the RNA polymerase or by forming a bend in the DNA.nteracting with the RNA polymerase or by forming a bend in the DNA.by forming a bend in the DNA.
answer9
"answer9"
buttonUp
buttonUp
answer9
Question 9:
Eight electrostatic interactions stabilize the T state. All eight electrostatic bonds involve the C- terminal amino acid residues of either the a or b subunits.e promoter by 100 fold. The result of this is that when lactose enters the cell the RNA polymerase is ready to start transcription immediately, leading to very quick production of the proteins.
answer8
"answer8"
buttonUp
buttonUp
answer8
Question 8:
The a1/b2 and a2/b1 contacts are altered in the transition from T to R state.....ucose concentration has no effect on the lactose concentration or the allolactose concentration. on or the allolactose concentration. enters the cell the RNA polymerase is ready to start transcription immediately, leading to very quick production of the proteins.
answer7
"answer7"
buttonUp
buttonUp
answer7
Question 7:
Haem has a Fe(II) atom chelated at its centre..... transcription. In the absence of cyclic AMP the CAP cannot bind to the CAP site so the promoter remains relatively inefficient. Thus only small amounts of permease made leading to low lactose uptake into the cell. is made so only a small amount of lactose enters the cell. uction of the proteins.
answer6
"answer6"
buttonUp
buttonUp
answer6
Question 6:
There are two types of subunit a globin and b globin.....It is the complex between the two that can bind to the CAP site. ecient. It also leads to the reduced entry of lactose because only a small amount of permease is made so only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins.
answer5
"answer5"
buttonUp
buttonUp
answer5
Question 5:
Haemoglobin is a tetramer with 4 subuints, 2 a globins and 2 b globins. ds to the reduced entry of lactose because only a small amount of permease is made so only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins.
answer4
"answer4"
buttonUp
buttonUp
answer4
Question 4:
Haemoglobin is unusually rich in a helices and contains very little pleated sheet. In this respect it is a typical protein. Haem is hydrophobic and is held in a hydrophobic pocket.
One BPG molecule binds in the centre of haemoglobin which is an archetypal allosteric protein. ll. ion immediately, leading to very quick production of the proteins.
answer3
"answer3"
buttonUp
buttonUp
answer3
Question 3:
In normal working tissues the amount of oxygen unloaded by a single red cell is 80% but this could vary somewhat depending upon the exact circumstances. lactose because only a small amount of permease is made so only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins.
answer2
"answer2"
buttonUp
buttonUp
answer2
Question 2:
The concentration of oxygen in blood is 0.01M 100 x greater than in plasma (0.0001M). The concentration of oxygen in the red cell is 200 x that in plasma.
nly a small amount of permease is made so only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins.
The answers to the problems that you got wrong can be seen below. Once you have read the correct answer click the mouse in the white box to move onto the next answer.
Answers to Haemoglobin Questions
NextPage
default
buttonUp
buttonUp
default
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
answer
1st Page
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
ExitProgram
buttonUp
buttonUp
The Effect of BPG on the T to R State Equilibriumnnn
The effect of BPG on haemoglobin depends, to some extent, on the partial pressure of oxygen. In the lungs (pO =100mmHg), 5mM of BPG is incapable of altering the T to R state equilibrium significantly, therefore haemoglobin is found to be all in the R state and fully oxygenated. A BPG concentration of 10mM also has no effect.
In working tissue (pO = 40mmHg), BPG shifts the equilibrium towards the T state causing haemoglobin to unload most of its bound oxygen.The higher the BPG concentration the greater the shift towards the T state. In highly active tissue (pO = 20mmHg), BPG shifts the equilibrium further towards the T state. This allows haemoglobin to unload almost all its bound oxygen........................................................a o
The following page illustrates the above.nds to the T state of haemoglobin........nnnnn..
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
Aims and Objectives
Introduction
This program is intended for use by students in their first or second year taking Biochemistry as part of their course. The program makes use of animations to illustrate the dynamic aspects of the structure and functions of Haemoglobin. The aims and objectives are as follows:
1. To illustrate the structural features of haemoglobin.
2. To illustrate the binding properties of haemoglobin for oxygen and how these
determine its ability to deliver oxygen to working tissues.
3. To illustrate the influence of hydrogen ions and 2,3-BPG on the ability of
haemoglobin to bind and deliver oxygen to working tissues.
4. To test your understanding of the tutorial by means of a multiple-choice quiz.hoice quiz.tanding of the tutorial by means of a multiple-choice quiz.rstanding of the tutorial by means of a multiple-choice quiz.
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
The Effect of Carbon Dioxide on Oxygen Affinityyy
In aerobic metabolism about 0.8 molecules of CO are formed per O molecule consumed. Most of the CO in the blood is carried in the form of bicarbonate, which is formed in red cells by the action of carbonic anhydrase..................................................................................................................................
~ n "
Much of the H generated by this reaction is taken up by deoxyhaemoglobin as part of the Bohr effect. The CO is carried by haemoglobin in the form of carbamate. The bound carbamates form salt bridges that stabilize the T state. Hence, the binding of carbon dioxide lowers the oxygen affinity of haemoglobin. cells by the action of carbonic anhydrase.
Carbamate
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
"mplayer.exe b:\hb-jmb.avi"
buttonUp
buttonUp
mplayer.exe b:\hb-jmb.avi
T-R transition
To access the video:
1. Press the "T-R Transition" or "Subunit" buttons below.
2. The Media Player (above) & Haemoglobin/Subunit molecule will be displayed.
3. To play the video, simply click the "Play" button.
4. To stop the video, click the "Stop" button.
5. To exit the Media Player, select the "File" menu and select "Exit".
:PHYSSIZE
:PHYSSIZE
OTHERWISE IT COULDN'T BE SIMPLER !!
PLEASE DO NOT TOUCH ANY OTHER BUTTONS OR MENUS.
guide
:PHYSSIZE
Button
"mplayer.exe b:\haem2.avi"
buttonUp
buttonUp
mplayer.exe b:\haem2.avi
Subunit
"a1b1"
"a2b2"
"a1b2"
"a2b1"
enterPage
leavePage
enterPage
leavePage
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
The R State.......
"a1b2"
mouseenter
mouseleave
mouseenter
mouseleave
"a2b1"
mouseenter
mouseleave
mouseenter
mouseleave
"a1b1"
mouseenter
mouseleave
mouseenter
mouseleave
alpha1
beta1
"a2b2"
mouseenter
mouseleave
mouseenter
mouseleave
beta2
alpha2
The subunits of the R state are held together by hydrophobic interactions. The major interactions involve approx. 35 amino acids and link the a to the b subunits. These are known as the a1/b1 interactions and are identical to the a2/b2 contact areas. These bonds stabilize the basic a/b dimer.Two dimers are linked to form the tetramer by smaller hydrophobic interactions that involve approx. 19 amino acids and are referred to as the a1/b2 and the identical a2/b1 contacts.............................................11
a1/b1
contactt
a2/b2
contactt
a1/b2
contactt
a2/b1
contactt
Move the cursor over the subunit contacts to display their identity.
Summary
Introductionnnnnn
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
1. Haemoglobin is the major oxygen carrier in blood
2. Haemoglobin has four subunits and is an allosteric protein
3. Haemoglobin can exist in two conformational states - R and T
4. Oxygen binds to haemoglobin in a cooperative manner
5. Oxygen binding promotes formation of the R state
6. H ions, 2,3-BPG and CO all bind to haemoglobin in the T state and in
doing so promote the R to T transition and thus the release of oxygen
7. The physiological consequences of these effects are illustrateddddd
As ca
Basic
NextPage
default
buttonUp
buttonUp
default
backPage
Previous
default
buttonUp
buttonUp
Previous
default
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
> Q U
animation illustrates the effect
high altitudes on
percentage
--oxygen released
>tissues.
sysCurosr
shows
d increasing
sea level(0)
4500m
"4500m"
"Matterhorn"
"Nanda Devi"
"Everest"
"Ap45"
"Ap75"
"Ap90"
"VO2"
"VO21"
"VO290"
default
compensatory result
increased BPG concentration
erythrocytes
=4500m
"sea"
4500m
7500m
levels
"7500m"
7500m
9000m
"9000m"
adaptation
(9000m)
decrease
venous pO2
buttonUp
buttonUp
4500m
altitude
Matterhorn
Nanda Devi
Everest
VO290
Matterhorn
Nanda Devi
Everest
VO290
7500m
altitude
Nanda Devi
Everest
Matterhorn
VO290
9000m
altitude
Everest
Nanda Devi
Matterhorn
VO290
Everest
Nanda Devi
Matterhorn
VO290
altitude
Everest
Nanda Devi
Matterhorn
VO290
default
sysCurosr
animation illustrates the release
oxygen
d blood cell
tissues.
"rp1"
-2370, 1980
"text1"
"text2"
"textGo"
H1500, 400
H1500, -400
H1500, 400
H1500, -400
Ungroup
4110, 765
4605, 630
3510, 675
4530, 975
3885, 1005
5070, 750
3240, 825
5625, 540
"81"
"71"
"rp2"
H1500, 400
H1500, -400
H1500, 400
H550, 0
3630, 1980
4770, 2470
4545, 2040
4400, 2555
3885, 2640
3950, 2005
3660, 2090
3655, 2380
4060, 2010
Group
-2370, 1980
default
buttonUp
buttonUp
text1
text2
textGo
WUngroup
text2
text1
textGo
text2
Group
default
This section contains 20 questions based on the information in the previous pages which will take about 10 minutes to complete. Once in the quiz it is only possible to go forwards - it is not possible to exit or return to previous pages.
N.B. For each question there are 5 checkboxes. The correct answer
may involve the checking of any number of boxes from 0 to 5.
GOOD LUCK!
Questions
Basic
Basic
NextPage
--see
--questscore1
question 1. It
zero
Fincreases
decreases depending on which answer boxes are
--same applies
questscores 2-20
--All forthcoming
fquestions on
have
Jlayout except
4questscore2
B"1a"
B"1b"
B"1c"
B"1d"
B"1e"
B"2a"
B"2b"
B"2c"
B"2d"
B"2e"
default
buttonUp
buttonUp
default
questscore2
questscore1
--removes cross
the answer boxes
"quest1"
"quest2"
leavePage
leavePage
quest1
quest2
quest1
quest2
1. How much oxygen can a single red blood cell potentially carry ?
5 million molecules
100 million molecules
200 million molecules
1000 million molecules
2000 million molecules
2. The oxygen concentration in blood is:
100 x the concentration in plasma
200 x the concentration in plasma
10 M
10 M
10 MM
Basic
"quest3"
"quest4"
leavePage
leavePage
quest3
quest4
quest3
quest4
3. What percentage of oxygen is unloaded by a red blood cell in actively-working
tissues? Select one value.
actose
4. Haemoglobin ::::::::::: working tissues has the following effects:of oxygen unloaded: of oxygen unloaded:of oxygen unloaded:
Has a high alpha helix content
Has a hydrophilic binding pocket for haem
Has a low beta pleated sheet content
Is an allosteric protein
Has four binding sites for BPG
NextPage
4questscore3
4questscore4
B"3a"
B"3b"
B"3c"
B"3d"
B"3e"
B"4a"
B"4b"
B"4c"
B"4d"
B"4e"
default
buttonUp
buttonUp
default
questscore4
questscore3
Basic
NextPage
4questscore7
4questscore8
B"7a"
B"7b"
B"7c"
B"7d"
B"7e"
B"8a"
B"8b"
B"8c"
B"8d"
B"8e"
default
buttonUp
buttonUp
default
questscore8
questscore7
illustration1
illustration2
illustration3
BPG & altitude
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
The Effect of BPG on Oxygen Binding in
BPG ( 2,3-Bisphosphoglycerate) binds to haemoglobin and has a large effect on its affinity for oxygen. This anionic organic phosphate is present in human red cells at about the same molar concentration as haemoglobin.
BPG binds specifically to the T state of haemoglobin in a 1:1 ratio. It binds within the central cavity of a haemoglobin molecule and interacts between the two b subunits. On oxygenation, when the molecule shifts to the R state, the BPG is extruded because the central cavity becomes too small. BPG opposes this shift to the R state and thus decreases the oxygen affinity by stabilizing the the T state. Increases in BPG concentration decrease the oxygen affinity further...................
"textGo"
"text1"
"rp1"
3050, 2350
"rp2"
-1210, 2425
"rp3"
-5890, 2405
"O2"
5025, 2115
"plasma"
4785, 2340, 5510, 2795
"plasma2"
4875, 1815, 5855, 2475
cell"
2790, 2055, 3765, 2745
cell2"
"box1"
"box2"
"key"
"text2"
"text3"
enterPage
enterPage
textGo
text1
plasma
plasma2
red cell
plasma
plasma2
red cell
red cell2
text2
text3
/z0j1
cell1
animation1
Animate
Press the "Animate" button.
rbc12
rbc13
rbc11
*$Q"v
rbc13
red cell
plasma
plasma2
Plasma
--- represents 5,000,000
oxygen moleculessssssssssssss
textGo
REPEAT ANIMATION OR MOVE TO THE NEXT PAGEEE
text3
In comparison a single red blood cell can carry 1000 million oxygen molecules i.e approx. 200 times more than the same volume of plasma can carry...
text2
A volume of plasma equivalent to the volume of a red blood cell
carries approximately
5 million oxygen molecules..........
(1x10 l))
text1
This animation illustrates the differences in the amount of oxygen carried by plasma and red blood cells.
LO9 l
$YA i
red cell2
D@3 7
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
1.Stryer. L . Biochemistry (Third Edition). Published 1988. Pages 143-176.
2.Voet.D & Voet.J.G. Biochemistry. Published 1990. Pages 210-244.
3. Jones.J.G. The structure and function of Human Haemoglobin. (Handout)...........................
Bibliography
Introduction
rX(F(F(
"a1b1"
"a2b2"
"a1b2"
"a2b1"
"a1a2"
enterPage
leavePage
enterPage
leavePage
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
The T State.......
The same a1/b1 contacts are found in the T state as they are not altered by oxygen binding. The a1/b2 contact in the T state is altered however; being shifted in position. This relative movement of the two dimers is primarily stabilized by eight extra electrostatic bonds that are only found in the T state. All eight electrostatic bonds involve the C- terminal amino acids of either the a or b subunits.
The narrower lines represent electrostatic interactions between a1/a2 (4), a1/b2, a2/b1 and intra b bonds (2).
mouseenter
mouseleave
mouseenter
mouseleave
mouseenter
mouseleave
mouseenter
mouseleave
"a1a2"
mouseenter
mouseleave
mouseenter
mouseleave
"ea2b1"
mouseenter
mouseleave
mouseenter
ea2b1
mouseleave
ea2b1
"ea2b1"
mouseenter
mouseleave
mouseenter
ea2b1
mouseleave
ea2b1
"a2b1"
mouseenter
mouseleave
mouseenter
mouseleave
"ea1b2"
mouseenter
mouseleave
mouseenter
ea1b2
mouseleave
ea1b2
"ea1b2"
"ea2b1"
mouseenter
mouseleave
mouseenter
ea1b2
mouseleave
ea2b1
"a1b2"
mouseenter
mouseleave
mouseenter
mouseleave
"a1b1"
mouseenter
mouseleave
mouseenter
mouseleave
"a1b1"
mouseenter
mouseleave
mouseenter
mouseleave
"a2b2"
mouseenter
mouseleave
mouseenter
mouseleave
"a2b2"
mouseenter
mouseleave
mouseenter
mouseleave
beta2
t!j!q!
a1/b1
contactt
a2/b2
contactt
f#>#c#
a1/b2
contactt
a2/b1
contactt
Intra b2
bond
Intra b1
bond
ea1b2
Electrostatic
a1/b2 bond
bond
ea2b1
Electrostatic
a2/b1 bond
bond
x'0'u'
Electrostatic
a1/a2 bonds
Move the cursor over the subunit contacts to display their identity.
Structure of Haemoglobinnnnnnn
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
Haemoglobin is a tetrameric protein composed of two pairs of identical subunits. In human adult haemoglobin these are the a and b subunits. The a subunit contains 141 amino acid residues and the b subunit contains 146 residues. Each subunit carries a haem molecule which is responsible for the binding of oxygen.
There are two main conformational states of haemoglobin. In the absence of oxygen the T state predominates. When this binds oxygen a new conformation is generated, the R state. If this happens in the crystal state the crystal cracks indicating that a change in conformation has occurred.
"rp1"
-2370, 1980
"text1"
"text2"
"textGo"
enterPage
enterPage
text1
text2
textGo
z0>244
7x:n<2>
A~CBE
K|M@O
cell1
Press the "Animate" button.
Animation2
Animate
Active Tissue (e.g Muscle )
S b%/
T l*M
6KJ ]
text1
On reaching the capillaries in working tissues the red blood cell unloads around 80% of the oxygen it carries which diffuses into the surrounding tissues.
textGo
REPEAT ANIMATION OR MOVE TO THE NEXT PAGEEE
text2
text2
The release of oxygen is promoted by the low [O ] in working tissues, the lower pH and the high [CO ]....VE TO THE NEXT PAGE
"textGo"
"text1"
"HMr"
"O21"
3595, 1895
"O22"
4570, 1895
"HMt"
"HMh1"
"HMh2"
"HMh3"
"HM1"
enterPage
enterPage
textGo
text1
4't(
+,-l.
3$5l6
7>8v9@;P<
T state
R statee
Animation5
Animate
Press the "Animate" button...
textGo
REPEAT ANIMATION OR MOVE TO THE NEXT PAGEEE
text3
Once two H ions are bound haemoglobin is able to change conformation to the T state..
text2
Approximately 3 H ions interact with haemoglobin. On interaction of the first H ion, the subunit attempts to snap the molecule to the T state but fails..
text1
The presence of higher levels of protons in capillaries of active tissue (e.g contracting muscle) promotes the release of oxygen from oxyhaemoglobin.
text4
The interaction of the third H ion will lock the molecule into the T state and promote the unloading of O from the molecule. One or possibly both O 's may leave......
The Effect of Protons on the Oxygen Affinityyynnnnnnnnnnnnn
Oxygenated
Deoxygenated
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
Binding of Oxygen by Haemoglobin.ggggggggggggggggggggggg
The binding of oxygen to the T state of haemoglobin involves large conformational changes. Oxygenation causes the Fe atom to move into the plane of the haem 'pulling' the proximal histidine with it. This motion initiates the conformational change from the T state to the R state. This conformational change is transmitted to the subunit interfaces resulting in the rupture of two electrostatic bonds that stabilize the T state. The equilibrium between the two states then shifts towards the R state. As more oxygen binds, two new electrostatic bonds and one hydrophobic interaction are weakened and there is a further shift in the T-R equilibrium. Thus the oxygen affinity increases with increasing saturation of haemoglobin...ith increasing saturation of haemoglobin...................................................
--This animation shows the effect
pH on oxygen binding
"HMr"
"O21"
"O22"
"H1"
-125, 2790
"H2"
8995, 2790
"H3"
8995, 1880
3595, 1895
3595, 1895, 4000, 2270
4570, 1895
"HMh1"
"HMh2"
"HMh3"
"HMt"
"HM1"
"text1"
"text2"
"text3"
"text4"
"textGo"
--A hydrogen
comes along
binds
fR state
haemoglobin
140, 2790
470, 2430
810, 2320
1265, 2430
1585, 2520
1825, 2790
2005, 2430
2245, 2320
2415, 2430
2630, 2520
2960, 2790
beta subunit
which
bound tries
change its conformation
but fails
3366, 2515, 4296, 3460
3321, 2515, 4296, 3460
8355, 2790
7725, 2430
7530, 2320
7170, 2430
6990, 2520
6825, 2790
6675, 2430
6495, 2320
6030, 2430
5680, 2520
5310, 2790
--On
ion,
alpha
fattached hydrogens convert
4296, 2505, 5181, 3460
3366, 2515, 4296, 3460
3321, 2515, 4296, 3460
4296, 2505, 5271, 3460
--following
conformational
subunits
whole molecule
--now
8225, 1880
7775, 1515
7415, 1375
7005, 1515
6825, 1650
6500, 1880
6290, 1515
5955, 1375
5695, 1515
5380, 1650
5210, 1880
--Now that
molecules are released
ZhorizPos
ZvertPos
4570
8970
forced
3640, 1895, 3965, 2270
3595, 1895, 4000, 2270
3640, 1895, 3965, 2270
3595, 1895, 4000, 2270
3640, 1895, 3965, 2270
3595, 1895, 4000, 2270
3640, 1895, 3965, 2270
2845, 1895
2760, 1895, 3165, 2270
2760
-260
H-100
, 1895
3595, 1895, 4000, 2270
default
buttonUp
buttonUp
text1
text2
text3
text4
textGo
text1
text2
text2
text3
text3
text4
text4
textGo
default
horizPos:by
horizPos:to
vertPos
horizPos
5dLZX
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
Interaction of BPG with the T state of Haemoglobin
a NH
His 2
His 143
His 2
His 143
TJo
$ 8D/
DvD}D
B DR
Lys 82
Lys 82
--these
situation between
oxygen tension
BPG=5
shows
decreasing
40mmHg
change
made
bpg=5
M=100
"1"=5580
"2"=4470
"barchart"
5760, 3450, 6735, 3750
"HM1"
"HM2"
"HM4"
"HM5"
"HM12"
"HM22"
"HM42"
"HM52"
"HM11"
"HM21"
"HM31"
"HM41"
"HM51"
further
"1"=5580
"2"=5760
6225, 3450, 6735, 3750
returns
6bar (
"1"=5580
"2"=6225
4470, 3450, 6735, 3750
occurs
"1"=4470
"2"=4470
5760, 3450, 6735, 3750
"1"=4470
"2"=5760
6225, 3450, 6735, 3750
"1"=4470
"2"=6225
"Barchart"
4470, 3450, 6735, 3750
"1"=6720
"2"=4470
5760, 3450, 6735, 3750
"1"=6720
"2"=5760
6225, 3450, 6735, 3750
"1"=6720
"2"=6225
4470, 3450, 6735, 3750
buttonUp
buttonUp
barchart
barchart
barchart
barchart
barchart
Barchart
barchart
barchart
barchart
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
The Bohr Effectrotons on the Oxygen Affinityyynnnnnnnnnnnnn
Hydrogen ions also have an effect on the T-R equilibrium.
The transition from T state to R state involves the release of approximately one hydrogen ion per subunit. Thus, because hydrogen ions are involved in the T-R state transition, their concentration and therefore the pH will influence the position of that equilibrium.
Lower pH (higher hydrogen ion concentration) will favour formation of the T state. This in turn will reduce the oxygen affinity of haemoglobin.....
The next few pages illustrate the Bohr effect.
BPG & altitude
"Ap45"
"Ap75"
"Ap90"
"VO290"
"VO21"
"Everest"
"Nanda Devi"
"Matterhorn"
"sea"
"Altitude"
enterPage
enterPage
VO290
Everest
Nanda Devi
Matterhorn
Altitude
text1
However, at these altitudes, the venous pO decreases, therefore allowing Hb to deliver approximately 20% oxygen to the stressed tissues.lood.ry.ry.........2 decreases to allow 20% oxygen to be unloaded.
text1
At an altitude of 9000m, the difference between arterial and venous pO is so small that only
approximately 5% oxygen is unloaded by Hb.ood.ry.ry.........2 decreases to allow 20% oxygen to be unloaded.
As the altitude increases the effect of increased BPG concentration cannot help, therefore the amount of oxygen unloaded by Hb declines..blood.ry.ry.........2 decreases to allow 20% oxygen to be unloaded.
text1
When the arterial pO drops to 55mmHg, as it does at an altitude of 4500m, the amount of oxygen unloaded is reduced to 30% in non-adapted blood.y.ry.........2 decreases to allow 20% oxygen to be unloaded.
change alltitude
Change Altitude
Altitude
Altitude
0000m
Sea level
Everest
Everest
R!*!O!
(mm Hg)
% Saturation
n%F%k%
Z&2&W&
Nanda Devi
Nanda Devi
Normal BPG
High BPGGG
Amount of O
unloaded eeeeee
VO290
Venous pO
at 9000m
Arterial pO
at 9000mmmllll
Arterial pO
at 7500mmmllll
Venous
pO
D6:6A6
Venous
pO
Arterial
pOt sea levellllll
Arterial pO
at 4500mmmllll
Matterhorn
Matterhornnn
High altitude adaptation raises the (BPG), which decreases the affinity of Hb for O .The amount of O unloaded is thus restored to 38% of its maximum load................................
At sea level, where arterial and venous pO values are 100 and 30mmHg respectively, Hb normally unloads 38% of the oxygen it can carry maximally..;F
You can distribute the unmodified material freely and modify it to your own
requirements. However, we ask the following:
1. By all means give yourself credit for your work in your books but please
leave this page unaltered in this book.
2. It is important that teaching material of this kind is disseminated as widely as
possible, so please ensure that your material is also freely available.
3. Please send a copy of any modified or expanded versions of this program to
Dr J.M Basford, Department of Biochemistry, University of Wales, Cardiff,
CF1 1ST , Tel 44 222-874119 Fax 44 222-874116.
Internet Basford @Cardiff.ac.uk
default
buttonUp
buttonUp
default
Continue
:PHYSSIZE
Teaching and Learning
Technology Programme
Haemoglobin
default
buttonUp
buttonUp
default
Start
produced by the
R. Emma Thomas & John M. Basford
Biochemistry Department
University of Wales, Cardiff............
"rp1"
3050, 2350
"rp2"
-1210, 2425
"rp3"
-5890, 2405
"O2"
5025, 2115
"plasma"
4785, 2340, 5510, 2795
"plasma2"
4875, 1815, 5855, 2475
cell"
2790, 2055, 3765, 2745
cell2"
"box1"
"box2"
"key"
"text1"
"text2"
"text3"
"textGo"
--illustration begins
fthe flow
blood cells through a vessel.
H200, 0
H200, 0
H200, 0
H200, 0
H200, 0
H200, 0
H200, 0
H200, 0
H200, 0
H200, 0
shows
amount
oxygen carried
a volume
equivelant
-- a
sysLockSceen
5145, 1395, 6380, 2310
"O2"
5355, 1680
5505, 885, 7505, 2205
"O2"
5895, 1305
5640, 585, 8225, 2145
"O2"
6210, 1065
syslockScreen
5685, 255, 8510, 2100
"O2"
6435, 750
5640, 585, 8225, 2145
"O2"
6210, 1065
5505, 885, 7505, 2205
"O2"
5895, 1305
5145, 1395, 6380, 2310
"O2"
5355, 1680
4875, 1815, 5855, 2475
"O2"
5025, 2115
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
illustrates
2250, 1455, 3570, 2475
1410, 1005, 3345, 2295
735, 540, 3135, 2130
285, 255, 3075, 2100
735, 540, 3135, 2130
1410, 1005, 3345, 2295
2250, 1455, 3570, 2475
2790, 2055, 3765, 2745
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
H250, 0
default
buttonUp
buttonUp
plasma
plasma2
red cell
plasma
plasma2
red cell
red cell2
text1
text2
text3
textGo
text1
text2
plasma
plasma
plasma2
plasma2
333333
plasma2
333333
plasma2
333333
plasma2
plasma2
333333
plasma2
333333
plasma2
333333
plasma2
plasma2
plasma
plasma
text2
text3
red cell
red cell
red cell2
red cell
333333
red cell2
333333
red cell2
333333
red cell2
red cell2
333333
red cell2
red cell
red cell2
333333
red cell
333333
red cell
red cell
text3
textGo
default
sysLockSceen
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
Haem Molecule
The central iron atom is in the Fe(II) state and is coordinated to four nitrogen atoms from the porphyrin ring and one nitrogen from the proximal histidine residue in the globin subunit. The sixth coordination position is unoccupied until it binds oxygen.......................position is unoccupied until it binds oxygen.
"text1"
"Arrow"
7670, 4150
"RT1"
"RT2"
"RT3"
"RT4"
"TR1"
"TR2"
"TR3"
"TR4"
"text2"
"text3"
enterPage
enterPage
text1
Arrow
text2
text3
.v022
text3
At pH 7.2 and higher proton conc. more Hb molecules shift to the T state and as a result release their oxygen. The T:R ratio rises to 5:111111111111111111111111111111111e T state.
text2
At pH 7.4, the H ions promote the transition from R to T state and thus the release of oxygen from Hb molecules, thereby making the ratio approx. 2:1. favour of the T state.
T state
R statee
Arrow
Animation5
Change pH
The Effect of pH on the T to R Equilibrium
Press the "Change pH" button.
R H q
b#H
n%H q
"'H q
~(H
:*H
text1
text1
At pH 7.6 and a pO of 40mmHg the T-R state ratio for haemoglobin is 1:1. ween both conformational states (T and R). tional states (T and R).
Introduction
Introduction
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
In mammals the delivery of adequate amounts of oxygen to working tissues is of primary importance. The ability to deliver this oxygen is entirely dependent upon the capacity of red blood cells both to take up large quantities of oxygen in the lungs and to release most of this oxygen under the conditions in the working tissues. In working tissues the oxygen concentration is much lower, the pH is lower and the carbon dioxide concentration is much higher than in the lungs. The ability of red cells to deliver oxygen and to alter the magnitude of this delivery according to the conditions is dependent on the properties of haemoglobin, a protein exquisitely suited to this role.
"quest15"
"quest16"
leavePage
leavePage
quest15
quest16
quest15
quest16
15. After acclimatisation at an altitude of 4500m what effects occur ?
The BPG concentration in red cells increases
The amount of oxygen taken up in the lungs decreases
The amount of oxygen unloaded remains the same
The amount of oxygen unloaded increases
The pH value decreasessssssss
16. Which amino acid residue in the b subunit interacts with a hydrogen ion
and is implicated in the Bohr effect?
Lysine
Arginine
Histidine
Valine
Glycine
NextPage
4questscore15
4questscore16
B"15a"
B"15b"
B"15c"
B"15d"
B"15e"
B"16a"
B"16b"
B"16c"
B"16d"
B"16e"
default
buttonUp
buttonUp
default
questscore16
questscore15
backPage
Previous
default
buttonUp
buttonUp
Previous
default
NextPage
default
buttonUp
buttonUp
default
"7.6"
enterPage
enterPage
A lowering of pH shifts the oxygen dissociation curve to the right, so that the oxygen affinity is decreased, therefore more O
is unloaded in the tissues.
change pH
animation illustrates the effect
pH on
percentage
--oxygen released
6tissues.
shows
Vsituation
cpH decreases
change occurs only
pH=7.6
"7.4"
pH=7.4
"7.2"
pH returns
pH=7.2
"7.6"
buttonUp
buttonUp
Change pH
7.60m
Arterial pO
in capillaries llll
Amount of O
unloaded eeeeee
pH 7.6
pH 7.4
pH 7.2
text1
At pH 7.2, Haemoglobin releases about 10% more oxygen at the arterial pO of 20mmHg in active muscles than it does at pH 7.4........................................
text1
In the capillaries where pO is low, the H ions generated by bicarbonate formation are taken up by Hb, which is thus induced to unload its bound oxygen....
% Saturation
V . S
#X#}#
l$D$i$
(mm Hg) (Torr)
illustration3
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
Structure of BPG with Deoxyhaemoglobin
2,3 - Bisphosphoglycerate (BPG)
The binding site for BPG is constituted by three positively charged residues on each b chain:
the a-amino group, Lysine 82, and histidine 143. These groups interact with the strongly negatively charged BPG, which carries nearly four negative charges at physiological pH.
The following page illustrates how BPG binds to the T state of haemoglobin........nnnnn..
enterPage
enterPage
[8Y8Y*\*\
The Interaction Between Protons and Haemoglobinnnnnnnnnnnnn
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
C-terminal
{ d!9
MOVE ON TO NEXT PAGE AT ANY TIMEEEEEEEEEE
T state(deoxy))
R state (oxy)
C-terminal
JX"XGX
Aspartate 94 raises the pK of Histidine 146 in deoxyhaemoglobin, but not in oxyhaemoglobin. The proximity of the ve charge on Asp 94 favours protonation of His 146 in deoxyHb.Thus, in the transition from oxy to deoxyHb, His 146 acquires a greater affinity for H because its local environment becomes more vely charged.........................dddddd
"Arrow"= 7670
6920, 4150
"text1"
"text2"
"text3"
"RT1"
"RT2"
"RT3"
"RT4"
"TR1"
"TR2"
"TR3"
"TR4"
ZhorizPos
5405
2150
H-105
-, 1170
syslockScreen
5405, 1170
nthe
4820, 2415
4100, 2640
3230, 2475
2420, 2175
1895, 2010
5120, 2010
6200, 4150
ZvertPos
7370
3035
7370, 1050
6050
2975
H-123
, 2475
6050, 2475
7670, 4150
2975
6050
, 2475
2975, 2475
3035
7370
3035, 1395
2420, 2175
3230, 2475
4100, 2640
4820, 2415
5120, 2010
1895, 2010
2150
5405
, 1170
2150, 1170
default
buttonUp
buttonUp
Arrow
Arrow
text1
text2
text3
Arrow
Arrow
text3
text2
text1
Arrow
Arrow
text1
text3
text2
default
vertPos
horizPos:by1
horizPos:to1
horizPos
PdoHQd
HAEMOGLOBIN
Times New Roman
System
Times New Roman
Times New Roman
Times New Roman
System
Times New Roman
Symbol
Times New Roman
Times New Roman
Wingdings
Wingdings
Times New Roman
Times New Roman
Wingdings
Times New Roman
Arial
Symbol
Arial
Times New Roman
Times New Roman
System
Arial
System
Arial
Times New Roman
System
Times New Roman
System
System
System
Symbol
Times New Roman
Times New Roman
Times New Roman
Times New Roman
Times New Roman
Symbol
Arial
mes New Roman
Symbol
Times New Roman
Times New Roman
Times New Roman
Times New Roman
Times New Roman
Wingdings
backPage
Previous
default
buttonUp
buttonUp
Previous
default
NextPage
default
buttonUp
buttonUp
default
barchart
Change BPG concentration
Change
(BPG)))
v $ b
T state
R state
mmHg (Torr)
mM/ml
text6
At a pO of 40mmHg when BPG is absent, Haemoglobin is found to be between 75% saturated and fully oxygenated.
text3
Even if BPG were absent at a pO of 100mmHg, Haemoglobin would remain to be found all in the R state and fully oxygenated....
text2
A higher BPG concentration of 10mM has no effect on the T to R equilibrium when pO is 100mmHg. Thus Hb is all in the R state and fully oxygenated.
text1
At a BPG concentration of 5mM
(its normal concentration) and a pO of 100mmHg, Haemoglobin is all in the R state and fully oxygenated.
text9
At a pO of 20mmHg where BPG is absent, Haemoglobin is found to be mainly 50% saturated and flickering between the R and T state.
text7
At a pO of 20mmHg and a BPG concentration of 5mM Haemoglobin is found to be mainly 25% saturated and in the T state.
text8
In highly active tissues, where pO =20mmHg, 10mM BPG shifts the equilibrium almost entirely to the T state, inducing Hb to unload all its bound oxygen.
text4
At a pO of 40mmHg and a (BPG) of 5mM, the T to R equilibrium shifts towards the T state. Hb is approx 75% saturated with O
and mostly in the R state......
text5
At a pO of 40mmHg and a (BPG) of 10mM, the shift to the T state is greater. Hb is found to be approx 50% saturated with O
and with a T:R ratio of 1:1.. T state.ng between the R and the T state.
Change Oxygen tension
Change
tensionnn
# :4h
Oxygenated
Deoxygenated
Concccc
"text1"
"textGo"
"text2"
"text3"
"text4"
"text5"
"text6"
"O21"
nthe
-470, 210
"O22"
7480, 200
"O23"
8450, 2725
"O24"
-520, 2170
"HM1"
"HM2"
"HM3"
"HM31"
"HM4"
"HM5"
370, 1330
820, 1435
1300, 1525
1855, 1600
2440, 1660
2920, 1720
3220, 1795
3295, 1795, 3605, 2200
3190, 1795, 3605, 2200
3295, 1795, 3605, 2200
3190, 1795, 3605, 2200
3295, 1795, 3605, 2200
3970, 1795
3865, 1795, 4295, 2200
7865, 1390
7460, 1540
6980, 1690
6515, 1750
6065, 1750
5495, 1795
5495, 1795, 5840, 2200
5495, 1795, 5915, 2200
5495, 1795, 5840, 2200
5495, 1795, 5915, 2200
5495, 1795, 5840, 2200
4865, 1810
4865, 1810, 5270, 2215
ZhorizPos
8865
4865
H-100
2, 2710
-565
3865
, 2710
default
buttonUp
buttonUp
text1
textGo
text2
text3
text4
text5
text6
text1
text2
text2
text3
text3
text4
text4
text5
text6
text5
text6
textGo
default
horizPos:by
horizPos:to
horizPos
Buttons Used In The Following Pagess
ExitProgram
backPage
NextPage
FirstPage
1st Page
Move to the next page
Return to previous page
Return to the first page of
Exit to Windows
Animate
Animate
Animates the sequence of events on that page
Go on to the next page by clicking the
button below:
backPage
Previous
default
buttonUp
buttonUp
Previous
default
NextPage
default
buttonUp
buttonUp
default
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
Hotwords - These are words that are scattered round the text and are shown in italic, bold, underlined type and are larger than the surrounding text. They become active when the mouse operated cursor is placed over them.
Try pressing this Hotword now!
-- Puts the sentence
quotation marks
a dialog box which can be removed
Hclicking
"Activating a HOTWORD will present you
dthat may contain definitions, references, hints
tips, prompts
other forms
encouragement. Press OK
buttonDown
buttonDown
Activating a HOTWORD will present you with a dialog box that may contain definitions, references, hints and tips, prompts or other forms of encouragement. Press OK to continue
DeoxyHb is a taut molecule, constrained by eight salt links. Oxygenation does not readily occur unless some salt links are broken.e broken
text6
text4
Unliganded subunits in the R state have an increased oxygen affinity because they are already in the O --binding conformation.
text5
All the subunits are converted to the R state whether they are liganded or not.nliganded subunits in the R state have an increased O a
text4
text4
As more O binds, the strain, derived from the Fe--O bond energy,increases until it is of sufficient strength to snap haemoglobin into the R state.................
text3
This is because salt links must be broken to permit the binding of the first O . Fewer salt links have to be broken for the binding of subsequent oxygens. y
text2
The R state of haemoglobin has a much higher affinity for O than the T state. Therefore the binding of the first O molecule to the T state is difficult.es.getically less favoured than that of subsequent oxygen molecules.lly less favoured than that of subsequent oxygen molecules.
text1
The binding of O to haemoglobin enhances the binding of additional O to the same Hb molecule. i.e oxygen binds cooperatively to haemoglobin.......
Oxygenated
Deoxygenated
"text1"
"textGo"
"HM1"
"HM11"
"HM12"
"HM13"
"HM2"
"HM21"
"HM22"
"HM23"
"HM3"
"HM31"
"HM32"
"HM33"
"HM4"
"HM41"
"HM42"
"HM43"
"HM4a"
"HM41a"
"HM42a"
"HM43a"
"HM5"
"HM51"
"HM52"
"Arrow"
4520, 4120
m"L2"
m"L3"
m"L4"
"p50"
enterPage
enterPage
text1
textGo
HM41a
HM42a
HM43a
Arrow
&L'x'
'((T(
(|)z*x+v,
HM43a
# R!W
Animation4
Animate
Press the "Animate" button.
Q **n
HM41a
HM42a
Q &,V
T state
R state
p/H/m/
(mm Hg) (Torr)
r0J0o0
^161[1
Arrow
textGo
REPEAT ANIMATION OR MOVE TO THE NEXT PAGEEE
text3
Haemoglobin is 50% saturated at an oxygen partial pressure of 26mmHg (Torr).
At 100mmHg p O , haemoglobin is 95% saturated.
text2
The O dissociation curve of Hb is sigmoidal in shape.Thus the amount of O bound by Hb changes significantly over a relatively small range of p O .
text1
The oxygen saturation of haemoglobin depends on the partial pressure of oxygen(p O ) than it would if O binding sites were independant of each other....................
"Arrow"
nthe
4520, 4120
"HM1"
"HM11"
"HM12"
"HM13"
"HM2"
"HM21"
"HM22"
"HM23"
"HM3"
"HM31"
"HM32"
"HM33"
"HM4"
"HM41"
"HM42"
"HM43"
"HM4a"
"HM41a"
"HM42a"
"HM43a"
"HM5"
"HM51"
"HM52"
m"L2"
m"L3"
m"L4"
"p50"
"text1"
"text2"
"text3"
"textGo"
moves along "Oxygen tension" axis
ZhorizPos
4520
5420
-, 4120
--conformational change
one alpha chain
%oxygen binds
syslockScreen
continues
5420
5735
, 4120
m"L2"
5735
6080
, 4120
m"L3"
6080
6935
, 4120
m"L4"
--final
oxyhaemoglobin
6935
7850
, 4120
deoxyhaemoglobin undergoes
default
buttonUp
buttonUp
Arrow
HM41a
HM42a
HM43a
text1
text2
text3
textGo
text2
text1
Arrow
text3
text2
Arrow
HM41a
HM42a
HM43a
Arrow
HM41a
HM42a
HM43a
Arrow
Arrow
text3
textGo
default
horizPos:by
horizPos:to
horizPos
illustration1
"Deoxy"
"Oxy"
terPage
enterPage
leavePage
enterPage
Deoxy
Deoxy
Deoxy
leavePage
Deoxy
When the sixth coordination position is occupied by oxygen the iron atom moves into the plane of the haem molecule. The proximal histidine (F8) is pulled along with the iron atom and becomes less tilted. This movement initiates the conformational change from the T state to the R state.
Histidine F8
Porphyrin
planee
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
MOVE ON TO NEXT PAGE AT ANY TIMEEEEEEEEEE
Deoxy
barchart
--the equilibrium between deoxyhaemoglobin
varies depending
--on
Aconcentration
Xblood.
--changing
llength
vorange bar (
/) causes a alteration
--these
situation
oxygen tension=100
shows
increasing
change
made
bpg=5
G=100
"1"=5580
"2"=4470
"barchart"
4470, 2445, 6735, 2745
"HM1"
"HM2"
"HM4"
"HM5"
"HM12"
"HM22"
"HM42"
"HM52"
"HM11"
"HM21"
"HM31"
"HM41"
"HM51"
"text2"
"text1"
"text3"
"text4"
"text5"
"text6"
"text7"
"text8"
"text9"
decreasing
occurs
BPG=10
"1"=4470
"2"=4470
6720, 2445, 6735, 2745
returning
"1"=6720
"2"=4470
5580, 2445, 6735, 2745
40mmHg
"1"=5580
"2"=5760
4470, 2445, 6735, 2745
"1"=4470
"2"=5760
6720, 2445, 6735, 2745
"1"=6720
"2"=5760
5580, 2445, 6735, 2745
increase
"1"=5580
"2"=6225
4470, 2445, 6735, 2745
"1"=4470
"2"=6225
6720, 2445, 6735, 2745
"1"=6720
"2"=6225
5580, 2445, 6735, 2745
buttonUp
buttonUp
barchart
text2
text1
text3
text4
text5
text6
text7
text8
text9
barchart
text3
text1
text2
text4
text5
text6
text7
text8
text9
barchart
text1
text2
text3
text4
text5
text6
text7
text8
text9
barchart
text5
text1
text3
text4
text2
text6
text7
text8
text9
barchart
text6
text1
text3
text4
text5
text2
text7
text8
text9
barchart
text4
text1
text3
text2
text5
text6
text7
text8
text9
barchart
text8
text1
text3
text4
text5
text6
text7
text2
text9
barchart
text9
text1
text3
text4
text5
text6
text7
text8
text2
barchart
text7
text1
text3
text4
text5
text6
text2
text8
text9
illustration2
terPage
enterPage
leavePage
enterPage
leavePage
MOVE ON TO NEXT PAGE AT ANY TIMEEEEEEEEEE
T state
R state
ExitProgram
"Really quit?"\
f"Yes"
SysSuspendMessages
buttonUp
buttonUp
Really quit?
FirstPage
buttonUp
buttonUp
1st Page
The a b contact acts as a binary switch that permits only two stable positions of the subunits relative to each other. Oxygenation causes a switch from the T to the R state.The structural changes accompanying the T to R transition break the salt links in a process driven by the Fe O bond's energy of formation.
(.txt)