Erythrocyte Biochemistry

Question 1

Structure of hemoglobin

Answer 1

Tetramer of four helical peptide chains (2 alpha and 2 beta globin chains in adults) with a heme group containing reduced iron (Fe2+) in the center

Question 2

T State of hemoglobin

Answer 2

occurs in the absence of oxygen

Question 3

R state of hemoglobin

Answer 3

occurs when oxygen binds

Question 4

Cooperativity of hemoglobin is exhibited by

Answer 4

When one oxygen binds a heme group within hemoglobin, it induces a conformation change in the ring (by pulling the iron into the plane of the ring) which induces a conformational change in other rings that make it bind oxygen more easily

Question 5

Effects of 2,3-BPG, H+, and CO2 on the oxygen dissociation curve of hemoglobin

Answer 5

All shift the curve to the right
2,3-BPG reduces the affinity of hemoglobin for oxygen
H+ – Bohr effect

Question 6

HBF

Answer 6

fetal hemoglobin
does not bind well to 2,3-BPG, therefore it has a higher affinity for oxygen than maternal hemoglobin - probably important

Question 7

Iron is absorbed by enterocytes in the _____ State

Answer 7

Fe2+ state

Question 8

Ferritin

Answer 8

stores Fe3+ in enterocytes

Question 9

Ferroportin

Answer 9

Transports Fe2+ out of enterocyte into lumen
activated by low dietary iron
inhibited by hepcidin and high dietary iron

Question 10

Hemochromatosis

Answer 10

caused by unregulated duodenal reabsorption of iron due to low levels of hepcidin
or (?)
deficient ferroportin results in an overabundance of iron - cirrhosis, arthritis, endocrinopathy, skin pigmentation, cardiomyopathy

treat with bloodletting

Question 11

Hepcidin

Answer 11

regulates iron content in the body
binds ferroportin when iron is high and causes it to be internalized and destroyed by proteolysis

when iron levels are low, hepcidin isnt expressed and doesnt tag ferroportin

regulated by Hfe (TF that binds trf2 to express hepcidin)

Question 12

Transferrin

Answer 12

transports Fe3+ to liver, spleen and bone marrow
activated by low stored iron
inhibited by high stored iron

Question 13

Iron deficiency consequences

Answer 13

fatigue and anemia
deficiency results from insufficient diet
depletion can occur from bleeding

Question 14

Iron overload consequences

Answer 14

Iron poisoning –>

1) Hemochromatosis
2) Hemosiderosis
3) Sideroblastic anemia

Question 15

Hemosiderosis

Answer 15

ferritin is degraded into insoluble hemosiderin which accumulates (in alcoholics and blood transfusion recipients)

alvealoar hemorrhage can result

Question 16

Sideroblastic anemia

Answer 16

impaired heme synthesis –> iron buildup in mitochondria

pale skin, fatigue, enlarged spleen

Question 17

B12 and B9 necessary for the production of

Answer 17

Red blood cells

deficiency of either can cause megaloblastic anemia due to diminished DNA synthesis

Question 18

N5-methyl THF (dietary folate) requires _____ to be _____ to become folic acid

Answer 18

cobalamin

demethylated

Question 19

Cobalamin is composed of

Answer 19

nucleotide, protoporphyrin like ring, cobalt, sugar, nitrogen ring

Question 20

Cobalamin is absorbed by

Answer 20

binding R binder proteins made by mucosa in stomach
pancreatic enzymes degrade R protein in the duodenum

Parietal cells also in the stomach release intrinsic factor, which picks up B12 in the duodenum and carries it to the ileum, where it is absorbed by cubulin

Question 21

R-binder proteins

Answer 21

produced by mucosa cells in the stomach

bind cobalamin in the stomach and carry it to the duodenum before it is degraded by pancreatic enzymes

Question 22

Intrinsic factor

Answer 22

produced by parietal cells in the stomach

binds cobalamin in the duodenum and carries it to the ileum where it is absorbed by cubilin

Question 23

Cubilin

Answer 23

receptor in the ileum that absorbs intrinsic factor bound cobalamin

Question 24

Transcobalamin

Answer 24

carries cobalamin in the blood

Question 25

Megaloblastic macrocytic anemia

Answer 25

Large erythrocytes - normal hemoglobin content in relation to size
can result from B6/B12 deficiency (co factors in DNA synthesis required for production of so many RBCs in a day)
Bone marrow will exhibit large erythroblasts and hypersegmented neutrophils

Question 26

Pernicious Anemia

Answer 26

Vitamin B12 deficiency as a result of lack of intrinsic factor (necessary for uptake in the duodenum) as a result of lack of gastric mucosa due to autoimmune diease or decreased protein production