O2 T&S

Question 1

0.003 mL O2/ 100 mL of blood

Answer 1

low solubility
small amount of O2 dissolved in plasma
require large volumes to supply increasing metabolic demand—> O2 transport proteins

Question 2

Oxygen transport proteins (Hemoglobin and Myoglobin)

Answer 2

bind and release O2 when supply levels is high and low

Question 3

Hgb and Mgb

Answer 3

same structural motif (secondary and tertiary structures)

different amino acid sequence

Question 4

Amino acids conserved in Hgb, Mgb (vital roles in oxygenation and deoxygenation)

Answer 4

1) His F8 and His E7 : oxygen binding site
2) Phe CD 1 and Leu F4 : HEME contact (hydrophobic pocket)
3) Gly B6: close approach of helices B and E

Question 5

Mgb

Answer 5

153 aa, folded 8-right-handed alpha helices (each 7-20 aa)
cyclic tetrapyrrole heme located in the hydrophobic crevice (porphyrin ring + Fe++)
storage and release of oxygen from RBC surface to mitochondria in aerobic ATP synthesis

Question 6

Hgb

Answer 6

64.4 kd heterotetramer
2 pairs of chain: alpha-like and non-alpha chain

75%: alpha helix and 25%: non-helical (leads to folding)
4 heme groups: 4 oxygen

Question 7

Heme

Answer 7

protoporphyrin + Fe

Question 8

Protoporphyrin ring

Answer 8

4 pyrroles linked by methenyl bridges

Question 9

Soret bond

Answer 9

conjugated double bonds
SHARP BONDS
deep red of heme
UV absorption at 400 nm

Question 10

PYRROLE RINGS

Answer 10

Vinyl, Methyl, Propionate attach to this

Question 11

Iron

Answer 11

centre of porphyrin ring; connected to 6 ligand by COORDINATE BONDS
(4 is caused by 4N of the porphyrin ring)
(5th: His F8)
(6th: for Oxygen)

Question 12

Oxygenation and Deoxygenation:

UNOXYGENATED Mgb and Hgb

Answer 12

0.03 nm outside plane of heme ring toward His F8 BUT upon + O2, moves within 0.01 nm of heme plane

Question 13

Oxygenation and Deoxygenation:

DEOXYGENATION of HGB

Answer 13

beta chains ROTATE 0.7 nm apart

Question 14

Oxygenation and Deoxygenation:

O2 + Mgb and Hgb

Answer 14

1st O2 : perpendicular to Fe++
2nd O2: 121 degrees to plane of heme -> away from distal histidine

***OPTIMAL BINDING ORIENTATION OF O2

Question 15

Oxygenation and Deoxygenation:

T and R configuration

Answer 15

quaternary states
T : lower affinity deoxy confor
R : higher affinity oxy confor

Question 16

Oxygenation and Deoxygenation: T to R

Answer 16

changes in sub-unit to sub-unit interaction

H bond, salt/ionic bridges, etc

Question 17

Oxygenation and Deoxygenation:

Deoxyhemoglobin

Answer 17

stabilized by inter and intra-subunit salt bridges (broken down upon oxygenation)
less bonding between units

Question 18

Oxygenation causes

Answer 18

1. 15 degree rotation of 1 pair of A2B2 relative to A1B1
2. breaking down to salt bridges
3. New H bond at A1B1
4. molecular rearrangements
5. decrease size in central cavity

Question 19

Kd

Answer 19

dissociation constant
wherein half of O2 is bound
[O2] at which half Mgb have O2

Question 20

P50

Answer 20

partial pressure required for 50% saturation

RELATIVE BINDING AFFINITY FOR LIGAND

Question 21

OXYGEN BINDING CURVE

Answer 21

Mgb: hyperbolic

Hgb : sigmoidal

Question 22

Mgb: hyperbolic

Answer 22

SATURATED RAPIDLY

p50 is at 2mm: high affinity of Mgb for O2

Question 23

Hgb: Sigmoidal

Answer 23

SATURATED SLOWLY

*cooperative binding: +O2 leads to addition of more O2

Question 24

Hill equation

Answer 24

logarithm of relationship of Y to pO2 and P50

Question 25

Hill plot

Answer 25

O2 dissociation line because of logarithm

Question 26

Hill coefficient (nH)

Answer 26

degree of cooperativity | >1 + coop

Question 27

Cooperative index

Answer 27

fold change in pO2 required to change Y from a value of 0.1 to 0.9 Mgb: 81 Hgb: 4.8

Question 28

Modulation of O2 affinity

Answer 28

Allosteric effectors: CADET | - happens when the binding of one ligand by a protein influences the affinities of remaining unfilled binding sites

Question 29

Bohr effect

Answer 29

response of Hgb to any pH change

Question 30

Central cavity is lined by positive charges

Answer 30

His 2, Lys 82, His 143, N of beta

Question 31

Factors affecting 2,3 DPG

Answer 31

anemia, age of RBC, acidosis and hypoxemia

Question 32

Models of : MoSY KoSe

Answer 32

Monod Wyman Changeaux : symmetry | Koshland Nemethy and Filmer: sequential (has intermediate conformations)

Question 33

HbA1c is affected by

Answer 33

Hemoglobinopathies decreased RBC life span hemolysis

Question 34

Hgbinopathies

Answer 34

mutation in gene

Question 35

Thalassemia

Answer 35

reduced synthesis of globin chain