Brainscape's Knowledge GenomeTM

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


See full index

Bio chem > Lecture 8 - Proteins in Action - Oxygen transport by Haemoglobin & Myoglobin (Allostery & Cooperatively in Haemoglobin) > Flashcards

Lecture 8 - Proteins in Action - Oxygen transport by Haemoglobin & Myoglobin (Allostery & Cooperatively in Haemoglobin) Flashcards

1
Q

Haemoglobin shape

A

Haem and Fe2+ in middle connected to helix by His F8

Deoxyhaemoglobin has dish shape

Oxyhaemoglobin has flat shape

Oxygen flatten haem and pulls His F8 and helix F towards binding site.

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
2
Q

R state

A

Relaxed
Oxyhaemo
Active

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

T state

A

Taut state
Deoxy
Stretched tight
Not as active

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

R- and T-states stabilised

by

A

steric interactions

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

Alternate side-chain packing in R- and T-states

Helices

A

F and C move one

turn past one another.

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

Haemoglobin is under

A

allosteric control of 2,3-bisphosphoglycerate (BPG)

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

Helices F and C move one turn past one another which …

A

Allows one sub unit to communicate with each other

Subunits are shifting relative to each other to get communication between them

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

2,3 BPG

A

Product of aerobic metabolism

Signal that a tissue is using a lot of oxygen.

Binds in site in middle of haemoglobin

-‘ve charge molecule, carboxyl group, 2 phosphate groups

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

BPG

A

Binds (stabilizes) to deoxy in T state by electrostatic interaction

Reduces oxygen affinity

Produced during respiration in peripheral tissues (conc higher in muscle than in lungs it will dump oxygen in tissue, and pick it up in the lung), promotes oxygen release where it’s needed

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

Cooperativity allows

A

efficient ‘unloading’.

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

Monomeric myoglobin has a

A

hyperbolic binding curve.

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

Cooperative, tetrameric haemoglobin has a

A

sigmoidal binding curve.

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

YO2 =

A

fraction of protein bound to O2

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

MWC, concerted model

A

For tetramer all subunits in T state or all in R state

Binding each substrate (S) shifts equilibrium in favour of R.

Subunits in a
low-activity, tense (T) or
high-activity, relaxed (R) conformation.

T state deoxyheme
R state oxyheme

monod, wyman, changeux

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

MWC, concerted model

Inhibitors (BPG) stabilise…

A

T state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q 
MWC, concerted model
Activators stabilise (push towards)...
A

R state

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

KNF, sequential model

A

One substrate binding induces a T to R conformational change in one subunit.

conformational change influences neighbouring
subunits (i.e. cooperativity), making them more likely to
bind substrate. Many conformations possible.

Explains negative cooperativity.

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

Concerted model describes

A

haemoglobin

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

Sometimes weaker binding is

A

better

20
Q

The first adaptation to high altitude increase BPG

A

shifts curve to right as it delivers more oxygen to the tissues.

Reduce Haemoglobin oxygen binding

21
Q

pH

A

Works through the binding site of BPG

Drop in pH favours BPG binding which favours oxygen release,

Higher pH in lungs

Lower pH in tissues

H+ bind to haemoglobin releases Oxygen

22
Q

CO2

A

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

binds to hemoglobin at the extreme N terminus

Influences BPG binding

23
Q

Bohr effect

A

Increase co2 and decrease pH (increase H+)

decrease affinity of haemoglobin for O2,

24
Q

what contributes to stabilising

the deoxy-Hb conformation.?

A

CO2 bind to extreme N-
terminal amino group

H+ protonate certain amino acid side chains

25
Q

O2 binding to Hb at lower pH

A

less tightly

26
Q

Cooperativity is prominent (important) only in presence of…

A

Allosteric inhibitors

27
Q

what Allosteric inhibitors stabilise T-state and unmasks

cooperativity?

A

BPG
CO2
H+

28
Q

What state is stripped hemoglobin absence of inhibitors in?

A

R state

Little cooperativity

29
Q

Do Foetuses hold oxygen tighter than adults?

A

yes

30
Q

Response to high altitude

A

Increase BPG
Decrease Hemoglobin O binding
Increase O delivery to tissues

31
Q

Foetus hemoglobin have different isoforms that Replace alpha and beta subunits found in adult hemoglobin
what are they?

A

ζ (Zeta)
ε (Epsilon)
γ (Gamma)

Better at binding O than adult isoforms

32
Q

Foetal isoforms

A

Better at binding O

Pick up O from placenta

Lack +’ve charge amino acids in BPG binding site

Doesn’t bind BPG well

Remains more in R state than T state

33
Q

Isoforms

A

Genetically different forms of an enzyme

34
Q

Methaemoglobin

A

Oxidation of haem Fe2+ to Fe3+

shifts one subunit to the R state conformation, without oxygen bound.

35
Q

Methaemoglobin Impairs function two ways:

A

binds oxygen less well.

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

36
Q

what does enzyme cytochrome b5 reductase do?

A

regenerates haemoglobin by reducing methaemoglobin back to Fe2+ state with transfer of electrons from NADH.

37
Q

HbM, or Boston haemoglobin

A

His E7 mutation to TyrE7
- cause Fe2+ to Fe3+

heme plane moves slightly & Breaks connection on Fe - His F8

38
Q

what state does HbM remain in?

A

T-state

low affinity for oxygen

39
Q

HbS, or sickle cell haemoglobin

A

‘sickle’ shape RBC get

stuck in blood capillaries

40
Q

What gain of function mutation does HbS have?

A

Hb b6 Glu to Val mutation

enables abnormal hydrophobic
interaction between Hb molecules, when in deoxy form,

cause polymerisation of Hb into chains that distort the red blood cells

41
Q

HbS

Hb β6 Glu to Val mutation

A

Hydrophobic on adjacent hemoglobin molecule build long fibres of hemoglobin

Long chains of tetramers associated with one another

Mutant val 6 sits within hydrophobic pocket that exists on all Hb molecules

Distorts RBC shape

42
Q

Haemoglobin function

A

Shifts tetramer to T state
Oxygen binding weakened allosterically by BPG, CO2
and low pH.

When shifted haemoglobin shows cooperative
binding of oxygen, shown in a sigmoidal binding curve.

43
Q

Whats shown in sigmoidal binding curve?

A

When shifted haemoglobin shows cooperative

binding of oxygen

44
Q

How does R and T state differ in Hemoglobin?

A

helix F interacts with

haem and helix C, and spacing between H helices.

45
Q

Physiological effects

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

Bio chem (36 decks)

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