51: Hemoglobin

Question 1

Myoglobin & Hemoglobin structures

Answer 1

confirmation of myoglobin and single globin monomer (β) of hemoglobin superimposable

key amino acids CONSERVED in correct place

Question 2

Myoglobin

Answer 2

8 helices, mostly α-helix

allows reversible binding of O2

Question 3

Ferrous Ion (Fe2+)

Answer 3

four bonds to nitrogen

one bond to globin protein

one bond free to reversibly bind oxygen

iron ion inside globin protein

Question 4

Hemoglobin A (HbA)

Answer 4

pair of identical
αβ dimers (α2β2
tetramer)

4 globin monomers, carries 4 O2

extensive interactions b/n the subunits: hydrophobic, ionic, hydrogen bonds

Question 5

Methemoglobin (metHb)

Answer 5

contains Fe3+ (ferric ion) in porphyrin ring

Fe2+ oxidized to Fe3+ when superoxide released instead of dioxygen

Ferric ion doesn’t bind to O2

Remaining 3 O2 sites don’t release oxygen that is bound

MetHb does not function as O2 carrier

Question 6

Blue people

Answer 6

Deficient in converting metHb to Hb

Question 7

Myoglobin curve

Answer 7

hyperbolic curve

Myoglobin has higher affinity for O2 than Hb

Question 8

Cooperative ligand binding

Answer 8

Binding of one O2 molecule promotes binding of another O2 molecule

First O2 binds with lowest affinity, last O2 binds with highest affinity

Question 9

O2 binding to heme

Answer 9

Fe ion slightly out of plane of heme ring

Fe atom (ferrous) moves into the plane of the heme when oxygenated

conformational change of Hb (tugging)

Question 10

αβ dimers

Answer 10

held together with a stronger interaction then dimer pairs to each other

Question 11

“T” (taut)

Answer 11

deoxyhemoglobin

Question 12

“R” (relaxed)

Answer 12

oxyhemoglobin

Question 13

2,3- BPG

Answer 13

negatively charged

negative allosteric effector

promotes formation of T state

allows the formation
of additional salt bridges
between the αβ / αβ dimers

decreases O2 affinity for Hb

Promotes unloading O2
in the tissues

Question 14

Hexokinase deficiency

Answer 14

Reduced 2,3-BPG levels

Left shift on binding curve

Increased O2 affinity

Question 15

Pyruvate kinase deficiency

Answer 15

Elevated 2,3-BPG levels

Right shift on binding curve

Decreased O2
affinity

Question 16

Bohr effect

Answer 16

pH decreases, Hb O2
affinity decreases

aerobic tissues form CO2 when producing ATP

CO2acts as an acid when it dissolves in H2O

CO2 and H+ ions signal a
need for more O2

Question 17

Carbonic anhydrase

Answer 17

promotes formation of carbonic acid from CO2

Allows formation of additional salt bridges
Stabilizes the taut form of Hb

promotes O2 delivery to tissues

Question 18

Carbamamino hemoglobin

Answer 18

CO2 react with the amino terminus of the α-chains

formation of additional
salt bridges

promotes O2 delivery to tissues

Question 19

Where does CO2 and H+ leave Hb, which promote the release of 2,3-BPG, as O2 binds?

Answer 19

Lungs

Question 20

In the lungs

Answer 20

high O2 atmospheric pressure in the lungs is
sufficient to overcome the T-state

O2 may bind
to Hb forcing out the 2,3-BPG, H+ ions are released

CO2 bound to the N-terminal end of
globin is released.

Question 21

In the tissues

Answer 21

CO2 and H+ ions bind to Hb, which promote the binding of 2,3-BPG, and
the delivery of O2

decreasing O2affinity in response to the decreased oxygen
tension in tissues

T state favored

Question 22

CO2 transported in blood as?

Answer 22

HCO3
CarbaminoHb
Dissolved CO2

Question 23

What is responsible
for a significant
proportion of acid
buffering during
CO2 transport?

Answer 23

Hemoglobin

Question 24

Carbon Monoxide

Answer 24

Free heme will bind to
CO 25,000x more tightly than to O2

CO bonds to Hg 200x
stronger then oxygen

Binding is reversible

Question 25

Carboxyhemoglobin

Answer 25

person who has 50% of Hb O2 binding
sites occupied by CO is near death (or dead)

cherry red appearance

“cherry red is dead”

Question 26

Carbon Monoxide Poisoning

Answer 26

Carboxyhemoglobin maintains high oxygen affinity

Use 100% oxygen

under elevated pressure (hyperbaric chamber)

Question 27

α-chain

Answer 27

same in all Hb’s (after

embryo)

Question 28

γ-chain

Answer 28

disappears soon after birth (HbF)

Question 29

δ-chain

Answer 29

found in low amounts in adults (HbA2)

Question 30

HbA (Adult)

Answer 30

α2β2

~90%

Question 31

HbF (Fetus)

Answer 31

α2γ2

~1%

Question 32

HbA2 (Adult)

Answer 32

α2δ2

~2%

Question 33

HbA1C (Adult)

Answer 33

α2β2-glycated

~5%

Question 34

What binds to 2,3-BPG less tightly, so it has slightly higher O2 affinity?

Answer 34

Fetal hemoglobin

Question 35

Persistent HbF

Answer 35

Some adults express α2γ2 at high levels

Benign condition

inducing may be cure for β-thalassemia and
sickle cell

Question 36

HbA1c levels

Answer 36

useful to monitor blood glucose levels over the previous three months

Question 37

β-globin glycation

Answer 37

N-terminus glycation

non-enzymatic, spontaneous reaction

Hb –> HbA1c

HbA1c no effect on Hb function

Question 38

Sickle Cell

Answer 38

Hemoglobin S (HbS)

Glu –> Val at position 6

HbS polymerizes, sickle

block blood flow

Causes tissue hypoxia leading to damage (infarcts)

does not alter
the oxygen carrying
properties of hemoglobin