Brainscape's Knowledge GenomeTM

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


See full index

biochem > Chapter 7: Hemoglobin and Myoglobin pt.1 > Flashcards

Chapter 7: Hemoglobin and Myoglobin pt.1 Flashcards

1
Q

Myoglobin relating to 3D structure

A

1st protein whose 3D structure was determined (by x-ray crystallography)

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

John Kendrew

A

used sperm whale myoglobin to determines myoglobin structure
-Mb has O2 storage/transport protein

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

Myoglobin facts

A

-monomer
-8 alpha-helices labeled A through H
-globular

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

Hemoglobin facts

A

-tetramer of 4 Mb like homologous subunits
*2 Alpha-globin and 2 Beta-globin subunits

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

Max Perutz (and Kendrew)

A

solved Hb’s crystal structure

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

Heme

A

*KNOW STRUCTURE S.4

-protoporphyrin IX + Fe^2+ = Heme
-1 heme (prosthetic group) per subunit
*prosthetic group: non-amino acid portion of a protein
-allows oxygen to bind

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

O2 binding pocket in heme general

A

-oxygen binds to the Fe^2+ that is in between 4 N
-His F8 (proximal HIS)
-Val E11
-His E7 (distal HIS)
-Phe CD1

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

How to determine oxy and deoxy Hb

A

-they have different wavelengths so diff colors
-color changes due to presence or absence of oxygen

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

O2 binding pocket in heme: His F8

A

-proximal His (8th residue on F helix)
-heme held in place to each Hb subunit/Mb by coordinate covalent bond to His F8
**connects Heme to Nitrogen of His F8

-keeps oxygen on the same face

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

O2 binding pocket in heme: His E7

A

-distal His
-forces any ligand binding to Fe (II) to bind and a BENT angle
*bent angle allows for O2 to bind Fe(II) on the heme reversibly

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

O2 binding pocket in heme: Val E11 and Phe CD1

A

holds heme in place through hydrophobic interactions

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

CO posioning

A

CO and other small molecules have a very strong affinity for Fe^2+ in heme
-when it binds linearly CO is 20,000 X stronger than O2

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

what helps prevent CO poisoning

A

-His E7: forces CO and any small molecules to bind Fe^2+ at a bent angle
*reduces their affinity for heme
(CO still poisonous but it would be worse without His E7)

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

Methemoglobin (metHb) and Metmyoglobin (metMb)

A

-what it is called (final) when Fe^2+ in presence of O2 gets oxidized to Fe^3+
-makes it so heme can not bind oxygen

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

diaphorase

A

enzyme that reduces Fe^3+ to Fe^2+
*allows oxygen to bind back to heme

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

Heme dimerization

A

-what the process ic called: Fe^2+ oxidized to Fe^3+ and harmful oxygen free radicals

-2 hemes can auto-oxidize through an intermediate where O2 bridges btwn two Fe (II) centers (heme dimers)
*Fe-O=O-Fe
*does not allow oxygen to bind

16
Q

How is heme dimerization prevented?

A

bulky groups (Val E11 and Phe CD1) in hydrophobic cleft prevent oxidation of Fe (II)
*allows for reversible oxygen binding

17
Q

O2 binding equation

A

YO2= pO2/ p50+pO2

*pO2 is the partial pressure
*p50=kd (amt of saturation req to get half oxygenation

-as p50 decreases, the affinity for oxygen increases
-creates a hyperbolic binding curve

18
Q

p50 of myoglobin

A

2.8 torr

19
Q

O2 binding equation: at half saturation

A

half saturation pO2= Kd= YO2

20
Q

Function of myoglobin

A

-it is a O2 storage protein
*gives up little O2 over normal physiological range

-under extreme conditions when O2 transport is not fast enough to meet the cells need - PO2 falls really low- allows Mb to release O2

21
Q

Hemoglobin function

A

transports oxygen from lungs to tissues
-dimer of dimers: can function like 2 subunits (AlphaBeta)2 dimer

22
Q

what does urea do to hemoglobin?

A

it break Hb into dimers (alpha1-beta1) and (alpha2-beta2)

23
Q

What did Perutz find in hemoglobin’s response to oxygen binding

A

-found change btwn the two states in Hb quaternary structure upon oxygen binding
*T-state and R-state
*switch occurs btwn surface of alpha1-beta1 and alpha2-beta2
*has a 15 degree twist between alpha-beta dimer pairs

24
Q

T-state

A

-“tense state”
-low affinity for oxygen
*no oxygen binded

-only state that has H-bonds and ion pairs

25
Q

R-state

A

-“relaxed state”
-high affinity for oxygen
*oxygen is binded

26
Q

Mechanism for Hb’s positive binding O2 binding cooperativity (perutz)

A

proposed that Hb’s cooperativity is from the mechanical movement of the protein scaffold
-like a domino affect

  1. T-state is locked in a tense conformation through H-bonds and ion pairs (not in R-state_
    *get energy from binding Fe2+ and oxygen to break the bonds
  2. Difficult for the T-state to bind the 1st oxygen bc His E7 and Val E11 block the 1st oxygen’s access to heme (sterically hinder)
  3. in T-state the Fe2+ is 0.6A out of heme plane
  4. Through the increase of [O2], the 1st oxygen is able to bind and pulls Fe2+ back into the heme plane
  5. His F8 is attached to Fe2+ so it also gets pulled towards the heme plane
  6. Bc His F8 is part of the F helix, it pulls the F helix like a lever on a fulcrum
    *F helix moves 1 A
  7. When F helix moves, the alpha-beta pairs rotate 15 degrees
    *change in quaternary structure
    *at the alpha1-beta2 and alpha2-beta1 contacts, different but equivalent sets of H-bonds and ion pairs act like knobs on a molecular switch (look at pic S.18)
  8. T–>R shift in quaternary struc causes His E7 and Val E11 to move out of the way
    *oxygen has clear access to the heme on the other 4 subunits
  9. The energy in the formation of the Fe-O2 bond formation drives the T–>R transition
27
Q

explanation of the sigmoidal shaped O2 binding curve

A

-T-state has a low affinity for O2
*low hyperbole
-R-state has a high affinity for O2
*high hyperbole

  • Hb is first in the T-state but then switches to the R-state- gives the oxygen saturation/binding curve
28
Q

positive cooperativity

A

O2 binding causes a shift from T to R-state in Hb
*need more than 1 subunit?

29
Q

myoglobin and cooperativity

A

does not exhibit any positive cooperativity bc it does not have a quaternary structure

-has hyperbolic saturation curve
-p50: 2.8 torr
*low p50=the faster the protein gets saturated=will bind “tighter”

30
Q

what is hemoglobins p50?

A

26 torr

31
Q

Perutz proof of hemoglobin binding oxygen mechanism

A

-he replaced His F8 with Glycine
-added Imidazole to heme

Found:
-normal Hb: cooperativity
-muated: no cooperativity (t-state)

32
Q

Hb function in O2 transport

A

IN LUNGS (pO2=100 torr):
-Hb is in R-state
-loads up on O2

IN CAPILLARIES (pO2=30 torr)
-Hb switches to T-state
-releases O2

biochem (13 decks)

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