Erythrocyte Biochemistry - Staudinger Flashcards
What are the two variants of adult hemoglobin? What is the fetal variant of hemoglobin? 4
Adult:
α2β2 - 97%
α2δ2 - 3%
Fetal:
α2γ2
What is the mutation occurring in sickle cell anemia
Glutamic acid (Glu) –> Val
Negative Neutral
Hydrophilic Hydrophobic
What is the effect of 2,3-BPG on hemoglobin
Reduces the O2 affinity for hemoglobin
What is positive cooperatively?
Hemoglobin binds O2 in a cooperative fashion. Each binding facilitates the next binding
What is the effect of pH on oxygen binding to hemoglobin? 10
Affinity for oxygen decreases with a decrease in pH (oxygen off-loading O2 in high CO2 environments)
Why does fetal hemoglobin have such a high affinity for oxygen? 11
2,3-BPG does not bind well to the gamma subunit of hemoglobin therefore oxygen affinity is increased
What form is iron stored in the liver as?
Ferritin
What form is iron in our diet?
Fe3+ (ferric form)
What converts iron from Fe3+ –> Fe2+?
Dcytb (duodenal Cytochrome b)
What transports Fe2+ into the enterocyte? 19
DMT1
What form of iron does transferrin transport? 20
Fe3+
What disease does iron deficiency result in? 22
Hypochromic macrocytic anemia
What occurs in hereditary hemochromatosis? 23
An excess of 15g of iron in the blood (normal –> 3-5g)
What is the role of hepcidin? 24
When high [Fe2+]
Hepicidin activity high
Ferroportin levels down
When low [Fe2+]
Hepcidin activity low
Ferroportin levels high
What is the role of hepcidin? 24
Binds to ferroportin and causes internalization of ferroportin into the enterocyte
What cofactors are required for RBC production? 27
Vitamin B12 - cobalamin
Folate
What causes megaloblastic anemia? 27
Deficiency of vitamin B12 and Folate
What is the first step in folate metabolism? 31
Reduction to THF by dihydrofolate reductase
What is the active form of Folate? 32
Tetrahydrofolate –> transfers carbon units from donors to acceptors (DNA syn)
What is referred to as a folate trap? 36
Occurs when B12 is not available resulting in folate staying as N5-methyl-THF
What does B12 do to N5-methyl-THF (folate)? 37
B12 removes the methyl group making:
THF (also called FH4)
B12-CH3
What happens when B12 enters the stomach? 39
B12 is bound by R Binders
Pepsin digests the complex and intrinsic factor binds B12
Intrinsic factor carries B12 to the ileum where receptors bring it into he body
What is the purpose of the shilling test? 43
To tell whether a B12 deficiency is due to problems with diet or absorption
What is the procedure during the schilling test? 43, 44
If Dietary:
Radioactively labeled cobalmin (B12) ingested, if shows up in urine the problem is dietary
If absorption:
Above procedure will not yield any B12 in the urine
repeat test with radioactively labeled cobalmin AND intrinsic factor
