Erythrocyte Biochemistry Flashcards
Proximal histidine; bound to heme
F8
Distal histidine; O2 binds to iron b/w heme and distal histidine
E7
Conformational change of Hb
O2 binds and pulls the proximal (F8) histidine of Hb down; changes the interaction with the globin chain
Positive Cooperativity
Binding of one O2 to one heme induces a conformational change to allow binding of O2 to another heme
2,3-BPG
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
Human Iron Distribution
Hemoglobin 67%
Storage Iron 27%
Ferritin (H2O soluble)
Hemosiderin (H2O insoluble)
Myoglobin 5%
Fe requiring proteins 1%Ferric Reductase
converts Fe3+ (non heme) to Fe2+
Divalent Transporter-1 (DMT1)
Takes up Fe2+
Ferroportin
Extrudes iron out of cell
Hephaestin/Cerruloplamsin
Converts free iron to Fe3+
Transferrin
Transports iron into blood
Regulates iron by binding to ferroportin, causing its internalization and destruction
Hepcidin
If high iron
hepcidin is up, ferroportin levels are down, and absorption of iron is low
If low iron
hepcidin is down, ferroportin is up, and iron absorption is up
Vitamin B12 (cobalamin) and folate (folic acid) deficiency; large erythrocytes (MCV > 100 fL)
Megaloblastic Macrocytic Anemia
Reduces FH2 or DHF to THF
Dihydrofolate Reductase
THF
Active form of folate; functions in transfer of carbon units from donors to acceptors; key in DNA synthesis
Folic Acid Absorption
Small intestine (jejunum); liver stores 5-10 mg folate which lasts 3-6 months; 50 micrograms per day needed
Why is cobalamin (B12) needed?
to methylate N5-methyl-THF; takes off and transfers to homocysteine forming methionine and THF
3 micrograms; not found in plant products; no animals can make, only microorganisms
B12
Ferrous Iron
Fe2+; animal products from bacteria
Ferric Iron
Fe3+; plants
B12 Absorption
B12 binds R binder; Cleaved by proteases and B12 binds intrinsic factor; intrinsic factor carries to ileum; endocytosis then carried through body by cobalamin
Folate Metabolism
Folate -> THF (DHFR x 2); serine methylene group added to make N5,10-methylene-THF which can go add to dUMp making dTMP
B12 Necessity
convert N5-methyl-THF (dietary) back to THF for pathway
