Erythrocyte Biochemistry Flashcards
Structure of hemoglobin
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
T State of hemoglobin
occurs in the absence of oxygen
R state of hemoglobin
occurs when oxygen binds
Cooperativity of hemoglobin is exhibited by
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
Effects of 2,3-BPG, H+, and CO2 on the oxygen dissociation curve of hemoglobin
All shift the curve to the right
2,3-BPG reduces the affinity of hemoglobin for oxygen
H+ – Bohr effect
HBF
fetal hemoglobin
does not bind well to 2,3-BPG, therefore it has a higher affinity for oxygen than maternal hemoglobin - probably important
Iron is absorbed by enterocytes in the _____ State
Fe2+ state
Ferritin
stores Fe3+ in enterocytes
Ferroportin
Transports Fe2+ out of enterocyte into lumen
activated by low dietary iron
inhibited by hepcidin and high dietary iron
Hemochromatosis
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
Hepcidin
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)
Transferrin
transports Fe3+ to liver, spleen and bone marrow
activated by low stored iron
inhibited by high stored iron
Iron deficiency consequences
fatigue and anemia
deficiency results from insufficient diet
depletion can occur from bleeding
Iron overload consequences
Iron poisoning –>
1) Hemochromatosis
2) Hemosiderosis
3) Sideroblastic anemia
Hemosiderosis
ferritin is degraded into insoluble hemosiderin which accumulates (in alcoholics and blood transfusion recipients)
alvealoar hemorrhage can result
Sideroblastic anemia
impaired heme synthesis –> iron buildup in mitochondria
pale skin, fatigue, enlarged spleen
B12 and B9 necessary for the production of
Red blood cells
deficiency of either can cause megaloblastic anemia due to diminished DNA synthesis
N5-methyl THF (dietary folate) requires _____ to be _____ to become folic acid
cobalamin
demethylated
Cobalamin is composed of
nucleotide, protoporphyrin like ring, cobalt, sugar, nitrogen ring
Cobalamin is absorbed by
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
R-binder proteins
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
Intrinsic factor
produced by parietal cells in the stomach
binds cobalamin in the duodenum and carries it to the ileum where it is absorbed by cubilin
Cubilin
receptor in the ileum that absorbs intrinsic factor bound cobalamin
Transcobalamin
carries cobalamin in the blood
