(11) Erythrocyte Biochemistry

Question 1

Structure of Hemoglobin:

Answer 1

Tetramer:

2 alpha globin chains
2 beta globin chains

Question 2

What portion of the hemoglobin has iron atom and carries O2?

Answer 2

Heme

Question 3

What are the three types of embryonic heme?

Answer 3

Hb Gower 1
Hb Gower 2
Hb Gower Portland

Question 4

When are embryonic Hb depleted?

Answer 4

after 8 weeks

Question 5

What hemoglobin type increases in fetal state?

Answer 5

Alpha and gamma

Question 6

What happens upon birth with hemoglobin?

Answer 6

Increase: Beta, delta

Decrease: gamma

Question 7

What is the composition of fetal hemoglobin?

Answer 7

Alpha2 GAMMA 2

Question 8

***Treatment of sickle cell anemia

What is the new approach?

Answer 8

Upregulate HbF

With use of HYDROXYUREA to induce HbF

Question 9

What is the importance of histidine in hemoglobin?

Answer 9

F8 histidine=Proximal histidine which is bound to HEME

E7 histidine=Distal histidine, binds to iron b/w the heme

Question 10

Describe the conformational change that occurs with O2 binding

Answer 10

O2 changes the position of iron in the plane of heme

-Pulls down the proximal F8 histidine of Hb and changes the interaction with associated globin chain

Question 11

Oxygen Dissociation Curves:

Hyperbolic curve for ______

Answer 11

myoglobin

Question 12

Oxygen Dissociation Curves:

Sigmoidal curve for _______

Answer 12

hemoglobin

Question 13

Oxygen Dissociation Curves:

What is the pO2 (torr) value measuring?

Answer 13

Percent Oxygen binding

Question 14

Describe positive cooperativity binding with Hb and O2:

Answer 14

Binding of one molecule of O2 to one heme facilitates the binding of an O2 to another heme

Question 15

Oxygen Dissociation Curve: Modulation by pH (BOHR EFFECT)

Drop of pH from 7.4 to 7.2

Answer 15

Causes a release of O2

*pH of actively respiring tissues is lower

Question 16

Oxygen Dissociation Curve: Modulation by pH (BOHR EFFECT)

What is the percent change for myoglobin vs hemoglobin in tissues vs lungs?

Answer 16

Myoglobin: 7%

Hemoglobin: 66%

Question 17

Modulation by 2,3-BPG

What happens with more 2,3-BPG?

Answer 17

Reduces affinity of O2 to allow to give up in tissues

Question 18

Modulation by exercise:

Drop in pO2 from 40 to 20 torr in __________ tissues corresponds to the steepest part of the oxygen binding curve

Answer 18

exercising

Question 19

Modulation by exercise:

Hb is very effective in providing oxygen to _______ tissues

Answer 19

exercising

Question 20

HbF ________ bind well to 2,3-BPG

Answer 20

does NOT

Question 21

What organ plays a key role in regulating the iron cycle?

Answer 21

LIVER

Question 22

Distribution of Iron in Humans:

What percentage of iron is in storage form? What are the forms iron is stored in?

Answer 22

27%

Ferritin- H20 Soluble
Hemosiderin - H20 insoluble

Question 23

Hereditary Hemochromatosis:

Clinical definition?

Answer 23

-TOO MUCH IRON

Organ dysfunction due to iron overload;

15g of total body iron

Question 24

What is hepcidin?

Answer 24

Regulator of iron homeostasis:

Binding of hepcidin to ferroportin causes internalization of ferroportin

Ferroportin destroyed by proteolysis

Question 25

RBC production is dependent on _______ and _______

Answer 25

Vitamin B12, Folate

Question 26

Deficiency of vitamin B12 and folate can cause a severe anemia called:

Answer 26

Megaloblastic anemia

Question 27

How does megaloblastic anemia occur?

Answer 27

Due to diminished synthesis of DNA in developing RBC in bone marrow

Question 28

Megaloblastic macrocytic anemia is characterized by:

Answer 28

LARGE erythrocytes