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Flashcards in Oxygen Transporters Deck (42):
1

what is myoglobin? what is the iron surrounded by?

the oxygen transporter of muscle
-4 nitrogens

2

describe the pocket that heme is tucked away in and why this is helpful

-non polar pocket, sequestered from water
-helps maintain the iron in a +2 state (nonoxidized)

3

why does oxygen bind more tightly to heme in myoglobin than carbon monoxide?

-steric hinderance
-O2 binds at a 120 degree angle which is preferred, CO binds perpendicularly

4

what happens to the myoglobin protein when O2 binds? what consequence does this have?

it changes shape (not very much)
-this has little to no consequence because REMEMBER myoglobin is monomer!! (no cooperative binding)

5

what general shape is myoglobin?

heical

6

what color is:
-oxygenated myoglobin
-oxidized myoglobin
-deoxygenated

-red
-brown
-blue

7

what are the roles of the two histidines found in myoglobin?

-one binds the oxygen, the other forms a ligand to the iron which moves when oxygen binds

8

what constitutes the subunits of Hb?

2 alpha and 2 beta

9

what is the shape of Hb?

globular

10

how many heme prosthetic groups does Hb have?

4 heme groups

11

what does the hill plot show and what does an n>1, =1, and <1 mean?

-this is a chart that shows if there is cooperative binding in a protein
-n>1 = yes, positive coop
-n=0= no cooperativity
-n<1 negative coop

12

in what range of oxygen pressures does myoglobin work and hemoglobin?

-myoglobin works in low O2 pressures such as muscle
-Hb works best in moderate O2 pressures throughout the body (works over a wider range)

13

Does the T or the R state of Hb bind oxygen more readily?

R (relaxed?), once one oxygen is bound, Hb moves into the R conformation
-the alpha will change the beta that it is tightly associated with and vice versa

14

why does the T form exist?

it is more stable in this conformation when not bound to oxygen

15

why is the T state of Hb more stable?

has more H bonds and electrostatic interactions
-more H bonds between the two ab dimers, specifically

16

How does CO2 effect the binding of Hb to O?

reduces the affinity for O2, allowing Hb to drop off O2 in tissues that have CO2 accumulating

17

what does H+ do to the affinity of Hb to O2?

reduces the affinity, allowing Hb to drop off O2 to tissues that have lactic acid accumulated

18

what is the haldane effect?

deoxygenated blood has a greater capacity to carry CO2 and vice versa

19

by what mechanism does H+ effect Hb?

it is a negative allosteric regulator ( does not bind to heme itself)

20

where does CO2 associate with Hb? what is the result of this binding?

the N terminal a-amino groups
-the carbamate stabilizes the deoxy form of Hb relative to the oxy, making CO2 a negative allosteric regulator

21

does CO2 bind heme?

no

22

how does BPG interact with on Hb?

binds to the beta subunit in a positively charged cavity

23

what affect does BPG have on Hb?

lowers its affinity for oxygen

24

when does BPG rise in the body?

in low oxygen environments (altitude)

25

what is the fetal form of Hb composed of?

a2gama2

26

what binds oxygen with a higher affinity, HbA or HbF?
-why?

HbF
-HbF has fewer positive charges in its corresponding pocket than HbA and HbF binds BPG less well

27

what do the two histidine residues on Hb do?

one forms a ligand to the iron, the other reduces CO binding

28

what are the three negative allosteric regulators of Hb?

CO2, H+, and BPG

29

what creates the sickle chape of sickle cell RBC's?

insoluble HbS

30

what is the change in amino acid in SS disease and where does this have an effect?

glutamate to a valine on the exterior of the beta subunit

31

how can sickle cell be diagnosed?

electrophoresis of Hb
-glutame (WT) is negatively charged and valine is neutral

32

sickling in SC patients is worse in high or low oxygen conditions?

-low, this is due to a hydrohpobic knob being present on the beta subunits of HbS which fits into the hydrophobic hole of alpha subunits of deoxy alpha subunits (this alpha hole is present in WT Hb as well, but not the beta knob)

33

what were the four treatments of SC discussed in class and their mechanisms?

-antibiotics: prevent secondary infection
-hydroxyurea: stimulates production of HbF which is normal
-BM transplant: replace HbS with HbA
-Gene therapy: works in mice, clinical trials underway

34

what is methemoglobin?

oxidized form of Hb (Fe3+) and cannot carry oxygen.

35

what is the clinical presentation of methemoglobin?

shortness of breath, cyanosis, mental status changes

36

how is methemoglobin diagnosed?

absorption spectrum of the blood

37

the ingestion of what can promote the formation of HbM?

nitrates and nitrites

38

what can help treat HbM?

reducing agents (vitamin C and methylene blue)

39

what is a thalasemia?

an imbalance in the synthesis of the alpha and beta subunits of hemoglobin

40

what ethnicity are thalasemias common in?

mediterranean, some south asian

41

what is the treatment for thalassemias?

blood transfusion

42

a mutation in what subunit of Hb causes SC?

beta