B4.024 Myoglobin and Hemoglobin in Medicine

Question 1

discuss the similarities between Hb and Mb

Answer 1

18% identical AAs
38% similar AAs
secondary and teriary structures v similar

Question 2

quarternary structure of Mb and Hb

Answer 2

Mb- monomer

Hb- tetramer a2X2

Question 3

different Hb tetramer isoforms

Answer 3

B, gamma, delta chains are similar and interchangeable
adult: a2B2
fetal a2y2
adult minor: a2d2

Question 4

can Mb tetramerize with Hb?

Answer 4

no

Question 5

prosthetic group and ligand for Mb and Hb

Answer 5

prosthetic: heme
ligand: O2

Question 6

how does binding to Mb or Hb alter heme’s properties?

Answer 6

1. protein hinders CO binding (heme usually binds CO 25000x tighter than O2)
2. protein inhibits O2 oxidization and inactivation of the iron within heme

Question 7

what happens if Fe in heme gets oxidized?

Answer 7

deactivates
can’t bind O2 anymore
loses its function

Question 8

discuss the color changing properties of Hb

Answer 8

appears blue when free, red when bound to O2

can see this color change at about 580 nm as O2 content increases

Question 9

discuss the shape of the Hb binding curve

Answer 9

displays cooperativity

multiple binding events

Question 10

discuss the shape of the Mb binding curve

Answer 10

simple hyperbolic

1 for 1 binding

Question 11

how do the differences in the Mb and Hb curves depict differences in their functions

Answer 11

Mb binds O2 more tightly, curve shifted to the left

-needs to be able to outcompete Hb to get O2 into tissues in times of depletion

Question 12

how does O2 cooperativity happen within Hb?

Answer 12

O2 binding induces a conformational change which creates a higher binding affinity

Question 13

what is BPG?

Answer 13

2,3-biphosphoglycerate

synthesized in erythrocytes from glucose in high concentrations

Question 14

discuss the relationship between BPG and HB

Answer 14

1 BPG binds each Hb tetramer between the B chains
binds to low affinity form but not to high affinity form
high [BPG] so many Hb bound

Question 15

discuss how BPG allostery affects Hb

Answer 15

facilitates a conformational change to deoxyHb

more BPG = less deoxyHb in equilibrium = more shift from oxyHb to deoxyHb to restore equilibrium

Question 16

without BPG, how would the Hb binding curve change?

Answer 16

would shift left, be closer to Mb curve

BPG weakens O2 affinity and enhances cooperativity, so without it Hb would just be happy to exist in its oxy form

Question 17

how is BPG regulated?

Answer 17

upregulated with hypoxia

lost during blood storage (one reason for blood bank shelf life)

Question 18

does fetal Hb have the same BPG binding properties as adult Hb?

Answer 18

fetal Hb has weaker BPG binding

fetus needs higher affinity Hb to take O2 from mothers blood like a MFing parasite

Question 19

what is the Bohr Effect

Answer 19

interaction of Hb with H+ and CO2
H+ weakens O2 binding
CO2 lowers O2 affinity by covalent and reversible binding at N-terminal amines

Question 20

what is the moonlight effect of Mb and Hb

Answer 20

change NO to NO3

during this process the Fe in the heme goes from Fe2 to Fe3 and Hb is inactivated (brown)

Question 21

discuss the presence of Hb in the lung

Answer 21

[O2] high
Hb saturated and in high affinity form
BPG forced to dissociate

Question 22

discuss the presence of Hb in the periphery

Answer 22

[O2] low
O2 dissociates, diffuses into tissue
Hb reverts to low affinity state
BPG binds and facilitates both processes

Question 23

should u hold your breath if your airplane cabin loses pressure?

Answer 23

seems like the only logical solution

Question 24

what happens to the Hb curve in the presence of drugs that oxidize Fe2 to Fe3?

Answer 24

oxidized heme cannot bind O2
so max binding is lower, fraction bound never reaches 100 bc Hb(ox) is useless
Hb(total)= Hb + Hb(ox) + Hb(O2)4

Question 25

what is methemoglobinemia?

Answer 25

when blood turns brown bc Hb(ox) can't bind O2

Question 26

antidote to methemoglobinemia

Answer 26

methylene blue | reduces Fe3 back to Fe2

Question 27

discuss CO poisoning

Answer 27

binds any protein with heme (wide reaching effects) binds at extremely low [CO] substoichiometric effect precludes O2 binding at one site, and enhances O2 binding at other sites

Question 28

what does substoichiometric effect | mean

Answer 28

can see effects with a single CO on an Hb tetramer, don't need all 4 sites bound

Question 29

how does CO poisoning affect the Hb curve

Answer 29

- can't carry as much O2 so lower max saturation | - can't release O2 it has, so enhanced affinity and left shift

Question 30

what is thalessemia

Answer 30

loss of a subunit of Hb stoichiometry messed up leftover subunits aggregate and precipitate low [] of useful Hb tetramers result in anemia

Question 31

why is synthetic blood a "holy grail"?

Answer 31

much preferred to blood transfusions to avoid viral infections, antigen matching, shelf life issues, religious objections

Question 32

why can't you put free Hb in blood?

Answer 32

can't withstand stress/pressures, dissociates into dimers and causes renal failure scavenges NO in blood vessels and causes BP spikes

Question 33

why can't Hb normally scavenge NO?

Answer 33

Hb usually contained within RBCs, and RBCs do not interfere with NO signaling due to cell free layer

Question 34

what are some ways that were considered to modify Hb to allow it to be put in blood freely?

Answer 34

covalently cross link tetramers copy Hb of ocean mammals that experience high pressures increase size to avoid NO zone (PEG modification)