Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BIOC192 > Lecture 8 - Gaymagaybloin > Flashcards

Lecture 8 - Gaymagaybloin Flashcards

1
Q

Haemoglobin evolved to be a ___

A

Tetramer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a Tetramer

A

Four globin proteins associated together non-covalently

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Oxygen binding changes the shape of

A

haem and haemoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does binding oxygen do to heme

A

Deoxyhaemoglobin has a dished haem.
- when oxygen is bound heme is closed to planar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens to the heam when oxygen binds

A

In oxyhaemoglobin, oxygen flattens the haem, and pulls histidine F8 and helix F toward the binding site.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What weakens oxygen binding

A

Anything that keeps helix F away will weaken oxygen binding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Oxygen changes…

A

Haemoglobins shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

O2 binding to oxyhaemoglobin does what?

A

Compared to deoxyhaemoglobin, O 2
binding to oxyhaemoglobin moves the
Fe2+ into the plane of the haem, draws His F8 down, and repositions helix F.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Binding of O2 to haemoglobin does what to orientation?

A

Shifts in the orientation of protein secondary elements, such as helix F moving relative to helix C, are called ‘conformational changes’.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Tense T-state =

A

Deoxyhaemoglibin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Relaxed R state =

A

Oxyhaemoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

When oxygen binds in one area….

A

The other areas become more susceptible to bind oxygen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

T state to relaxed =

A

Oxygenation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is 2,3-bisphosphoglycerate (BPG)

A

an allosteric inhibitor of O2 binding to haemoglobin
- moves it towards T state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Structure Of the allosteric effector 2,3-bisphosphoglycerate

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does the Positively-charged allosteric site include

A

Positively-charged allosteric site includes histidine and lysine sidechains and the amino termini of the b chains.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Haemoglobin is under allosteric control of

A

2,3-bisphosphoglycerate (BPG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

BPG binds to deoxy-Hb by..

A

electrostatic interactions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does BPG do in deoxy T- state do

A

BPG stabilises Hb in the
deoxy T-state, reducing
oxygen affinity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

When is BGP produced and what does it do

A

BPG is produced during
respiration in peripheral
tissues, so promotes
oxygen release where it
is needed.

21
Q

Proof that cooperatively allows effeint unloading

A

Monomeric myoglobin has a hyperbolic binding curve.
Cooperative, tetrameric haemoglobin has a sigmoidal binding curve.
YO2 = fraction of protein bound to O2

22
Q

How cooperatively allows efficient ‘unloading’

A

Monomeric myoglobin has a hyperbolic binding curve.
Cooperative, tetrameric haemoglobin has a sigmoidal binding curve.
YO2 = fraction of protein bound to O2

23
Q

How cooperatively allows efficient ‘unloading’

A

Monomeric myoglobin has a hyperbolic binding curve.
Cooperative, tetrameric haemoglobin has a sigmoidal binding curve.
YO2 = fraction of protein bound to O2

24
Q

Cooperatively is prominent only in..

A

Presence of allosteric inhibitors of binding

25
Q

In absence of inhibitors, “stripped haemoglobin” is predominately in the

A

R- state, so shows little cooperativity.

26
Q

Allosteric inhibitors BPG, CO2and H+ stabilise the

A

T-state. This unmasks cooperativity.

27
Q

What does CO2 do?

A

CO2 reduces O2 affinity, both directly and
via lowered pH of blood

28
Q

Process of CO2 reducing O2 affinity

A

Like BPG, elevated CO 2 and low pH (elevated H+) in metabolising tissues both reduce the affinity of haemoglobin for O 2, known as the Bohr effect.

Like BPG, CO 2 can bind to the at lower pH amino-terminal amino group, stabilising deoxy-Hb conformation in T-state.

29
Q

CO2 with haemoglobin equation

A
30
Q

In what case is weaker binding better?

A
  • the first substantial adaption to high altitude is an increase in BPG
  • this reduces haemoglobins oxygen binding
  • rightward shift of the binding curve delivers more oxygen to the tissues
31
Q

What alters the oxygen binding properties ?

A

Different amino acid sequences of normal haemoglobin subunits alter their oxygen binding properties

32
Q

What aspect of foetal haemoglobin have higher affinities for O2

A

Alternate isoforms

  • this allows the forest us to caplure oxygen in the placenta
33
Q

How foetuses hold oxygen tighter

A

Different amino acid sequences of normal haemoglobin subunits alter their oxygen binding haemoglobin haemoglobin properties.
Foetal haemoglobin includes alternate isoforms (,  & with )
higher affinities for O2.
This allows the foetus to capture oxygen in the placenta.

34
Q

How foetal haemoglobin being less sensitive to BPG leads to oxygen being bound more tightly

A

BPG binds to deoxy-Hb by electrostatic interaction.
The y chain replaces the B chain in foetal Hb. The y chain has serine place of a histidine found on the b chain’s binding
site for BPG.

35
Q

What does oxygen of haem Fe2+ to Fe3+ do?

A

Oxidation of haem Fe2+ to Fe3+ shifts one subunit to the R- state conformation, without oxygen bound

36
Q

Oxidation of haem Fe2+ to Fe3+ shifts one subunit to the R- state conformation, without oxygen bound -METHAEMOGLOBIN . This mutation impairs function two ways:

A

The methaemoglobin subunit does not bind oxygen despite otherwise being in the R-state, due to the Fe3+.

The three other subunits of the tetramer are shifted to the R-state, so do not release oxygen in the tissues as they should.

The enzyme cytochrome b5 reductase regenerates haemoglobin by reducing methaemoglobin back to Fe2+ state using transfer of electrons from NADH.

37
Q

His e7 can mutate to

A

Tyr (H58Y)

38
Q

His E7 mutation to Tyr (H58Y) changes..

A

.. the environment, causing Fe2+ to oxidise to Fe3+

-haem plane moves slightly, breaking the connection of Fe-His F8
- HbM remains in ‘T’ state, with low affinity for oxygen

39
Q

Sickle cell haemoglobin

A

The ‘sickle’ shape red blood cells get stuck in blood capillaries
This causes a range of secondary debilitating effects in the person

40
Q

HbS ‘gain of function’ mutation

A

The Hb b E6V mutation enables an abnormal hydrophobic interaction between Hb molecules, particularly when in the deoxy form, causing polymerisation of Hb into chains that distort the red blood cells. Recent trials of gene therapy are very promising

41
Q

Oxygen binding is weakened allosteically by…

A

BPG, CO2 and low pH

42
Q

When oxygen binding is weakened allostrically by BPG, CO2 and low pH, this can be describes as…

A

…shifting the tetramer to the T-state

43
Q

In presence of __,___ and ____, haemoglobin displays _____ binding of _____, evident in a ________ binding curve

A

In the presence of BPG, CO 2 and low pH, haemoglobin
displays cooperative binding of oxygen, evident in a
sigmoidal binding curve.

44
Q

How to the R- and T- states differ

A

The R- and T-states differ in how helix F interacts with the
haem and with the helix C, and spacing between H helices.

45
Q

Oxygen affinity is tuned in ____ and at ____ ______

A

Oxygen affinity is tuned in foetuses and at high altitude.

46
Q

Mutations to haemoglobin impair

A

Oxygen transport

47
Q

Sickle-cell anaemia results from

A

haemoglobin polymerisation.

48
Q

Haemoglobin function

A
  • Oxygen binding is weakened allosterically by BPG, CO2 and low pH.
  • This is described as shifting the tetramer to the T-state.
  • In the presence of BPG, CO 2 and low pH, haemoglobin
    displays cooperative binding of oxygen, evident in a
    sigmoidal binding curve.
  • The R- and T-states differ in how helix F interacts with the
    haem and with the helix C, and spacing between H helices.
49
Q

Physiological effects

A

• Oxygen affinity is tuned in foetuses and at high altitude.
• Mutations to haemoglobin impair oxygen transport.
• Sickle-cell anaemia results from haemoglobin polymerisation.

BIOC192 (38 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions