Erythrocyte Biochemistry

Question 1

Proximal histidine; bound to heme

Answer 1

F8

Question 2

Distal histidine; O2 binds to iron b/w heme and distal histidine

Answer 2

E7

Question 3

Conformational change of Hb

Answer 3

O2 binds and pulls the proximal (F8) histidine of Hb down; changes the interaction with the globin chain

Question 4

Positive Cooperativity

Answer 4

Binding of one O2 to one heme induces a conformational change to allow binding of O2 to another heme

Question 5

2,3-BPG

Answer 5

Shifts ODC to right by signaling Hb to let go of O2; reduces O2 affinity!; only in red blood cells; does not bind fetal hemoglobin well

Question 6

Human Iron Distribution

Answer 6

Hemoglobin 67%
Storage Iron 27%
     Ferritin (H2O soluble)
     Hemosiderin (H2O insoluble)
Myoglobin 5%
Fe requiring proteins 1%

Question 7

Ferric Reductase

Answer 7

converts Fe3+ (non heme) to Fe2+

Question 8

Divalent Transporter-1 (DMT1)

Answer 8

Takes up Fe2+

Question 9

Ferroportin

Answer 9

Extrudes iron out of cell

Question 10

Hephaestin/Cerruloplamsin

Answer 10

Converts free iron to Fe3+

Question 11

Transferrin

Answer 11

Transports iron into blood

Question 12

Regulates iron by binding to ferroportin, causing its internalization and destruction

Answer 12

Hepcidin

Question 13

If high iron

Answer 13

hepcidin is up, ferroportin levels are down, and absorption of iron is low

Question 14

If low iron

Answer 14

hepcidin is down, ferroportin is up, and iron absorption is up

Question 15

Vitamin B12 (cobalamin) and folate (folic acid) deficiency; large erythrocytes (MCV > 100 fL)

Answer 15

Megaloblastic Macrocytic Anemia

Question 16

Reduces FH2 or DHF to THF

Answer 16

Dihydrofolate Reductase

Question 17

THF

Answer 17

Active form of folate; functions in transfer of carbon units from donors to acceptors; key in DNA synthesis

Question 18

Folic Acid Absorption

Answer 18

Small intestine (jejunum); liver stores 5-10 mg folate which lasts 3-6 months; 50 micrograms per day needed

Question 19

Why is cobalamin (B12) needed?

Answer 19

to methylate N5-methyl-THF; takes off and transfers to homocysteine forming methionine and THF

Question 20

3 micrograms; not found in plant products; no animals can make, only microorganisms

Answer 20

B12

Question 21

Ferrous Iron

Answer 21

Fe2+; animal products from bacteria

Question 22

Ferric Iron

Answer 22

Fe3+; plants

Question 23

B12 Absorption

Answer 23

B12 binds R binder; Cleaved by proteases and B12 binds intrinsic factor; intrinsic factor carries to ileum; endocytosis then carried through body by cobalamin

Question 24

Folate Metabolism

Answer 24

Folate -> THF (DHFR x 2); serine methylene group added to make N5,10-methylene-THF which can go add to dUMp making dTMP

Question 25

B12 Necessity

Answer 25

convert N5-methyl-THF (dietary) back to THF for pathway