B4-024 Myoglobin and Hemoglobin in Medicine

Question 1

what is myoglobins quaternary structure?

Answer 1

monomer

Question 2

what is hemoglobins quaternary structure?

Answer 2

tetramer

Question 3

myoglobin and hemoglobin moonlight in the conversion of

Answer 3

nitric oxide to nitrate

Question 4

prosthetic group shared by both

Answer 4

heme

Question 5

why does the heme prosthetic group need to be bound to proteins?

2 reasons

Answer 5

1. free heme binds CO more tightly than O2
2. O2 oxidizes the iron in free heme

Question 6

the observed binding curve of hemoglobin is sigmoidal, indicating

Answer 6

cooperativity and multiple binding sites

Question 7

RBCs have a high concentration of […] allowing for the binding of many hemoglobin molecules

Answer 7

BPG

Question 8

excess BPG shifts the equilibrium to

Answer 8

deoxyHb

Question 9

excess O2 shifts the equilibirum to

Answer 9

OxyHb

Question 10

BPG preferentially binds to

Answer 10

deoxyHb

Question 11

the Bohr effect

Answer 11

as pH decreases O2 affinity lowers

excess H+ and CO2 signal tissues need more oxygen

Question 12

H+ ions […] O2 binding

Answer 12

weaken

Question 13

Co2 […] O2 affinity

Answer 13

lowers

Question 14

CO2 binds covalently and reversibly at

Answer 14

N terminal amines

Question 15

without BPG, what happens to Hb curve?

Answer 15

cooperativity is lost

Question 16

BPG is upregulated with

Answer 16

hypoxia

Question 17

BPG is lost during the

Answer 17

shelf life of blood

Question 18

how does increased BPG affect the binding curve?

Answer 18

shifts right

• decreased affinity
• allows oxygen to release more readily to tissues

Question 19

BPG does not bind well to fetal hemoglobin, What’s the benefit of this?

Answer 19

• increased affinity for O2
• easier for fetus to get oxygen

Question 20

how do high altitudes alter binding affinity?

Answer 20

decreased

curve shifts to right

Question 21

some OTC topical anesthetics oxidize

Answer 21

Fe2+ to Fe3+

cannot bind oxygen, maybe cause of SIDS

Question 22

effects of metheoglobinemia on binding curve?

Answer 22

cannot reach saturation

• limits oxygen able to carry
• doesn’t affect midpoint

Question 23

antidote for methemoglobinemia

Answer 23

methylene blue

Question 24

CO has an [….] affinity for heme

Answer 24

extremely high

Question 25

substoichiometric effects of CO on Hb

Answer 25

1 CO molecule takes up 1 binding site and increases affinity for O2 * can't carry as much O2 * can't release O2

Question 26

loss of a Hb subunit, results in aggregation of abnormal proteins and anemia

Answer 26

thalassemia

Question 27

How does Hb Kansas affect the binding curve?

Answer 27

* decreased cooperativity * decreased affinity * shifts midpoint right

Question 28

this hemoglobinopathy results in an unstable protein that dissociates, reducing the amount of Hb available for transport

Answer 28

Hb Kansas

Question 29

mutation causing Hb Kansas

Answer 29

beta Asn102Thr

Question 30

free Hb can cause extreme vasocontriction via

Answer 30

consumption of NO converting it to nitrate

Question 31

dimerization of free Hb causes

Answer 31

kidney damage

Question 32

oxidation of free heme causes

Answer 32

increased ROS

Question 33

* synthetic Hb from cross-linked human Hb * trialed in trauma setting * raised ethical concerns

Answer 33

polyheme

Question 34

* synthetic Hb made from cow Hb * KUMC used this successfully to treat Jehova's witness

Answer 34

hemopure

Question 35

normal adult Hb is composed of

Answer 35

2 alpha 2 beta subunits

Question 36

oxygenated Hb has a [...] affinity for O2

Answer 36

high

Question 37

deoxygenated Hb has a [...] affinity for O2

Answer 37

low | promotes release/unloading

Question 38

the protein component of Hb acts as a buffer for

Answer 38

H+ ions

Question 39

myoglobin has a [...] affinity for oxygen than Hb

Answer 39

higher

Question 40

myoglobin is composed of

Answer 40

a single polypeptide chain with one heme group

Question 41

Hb substitutes need to reduce the [...] that leads to a blood pressure spike

Answer 41

NO di-oxygenation reaction | decrease affinity for NO, increase Kd for NO

Question 42

the relationship between Kd and affinity is

Answer 42

inverse

Question 43

reduced affinity shifts the curve

Answer 43

right

Question 44

increased affinity shifts the curve

Answer 44

left

Question 45

BPG allosterically [...] the affinity of Hb for O2

Answer 45

lowers

Question 46

proton binding [...] the affinity and [....] pH

Answer 46

lowers lowers

Question 47

what causes methemoglobinemia?

Answer 47

nitrates | oxidize the Hb iron to Fe3+

Question 48

a left shifted O2 binding curve indicates

Answer 48

increased affinity

Question 49

allosteric mechanisms for lowering O2 binding affinity | 2

Answer 49

* Bohr effect * CO2 toxicity

Question 50

BPG preferentially binds the

Answer 50

deoxy Hb | allows more oxygen to tissues