It is a macrocytic anemia due to damage to the parietal cells which leads to a loss of intrinsic factor and eventually vitamin B12 deficiency
Folic acid’s conversion to tetrahydrofolate requires NADH or NADPH?
NADPH, not NADH! NADPH is used in biosynthetic reactions vs NDAH is used in energy metabolism, aka making ATP
What gets added to tetrahydrofolate to form methylene-THF?
A carbon group via serine or glycine
Methy-THF donates _____ group to ______ in order to generate methionine (for SAM)
Methyl
Homocysteine
Methylene-THF donates _____ group to form _____ which is important in ____. In addition to that, methylene-THF can also be modified to form ______ and _____.
Methylene
Thymidine
Nucleotide synthesis (thymidine is a pyrimidine deoxynucleoside)
Methyl and formyl
Formyl-THF donates _____ group in _____ biosynthesis
Formyl
Purine
Vitamin B12 (aka cobalamin) has two biological purposes:
Metabolize methylmalonic acid (converts it to succinyl CoA which is important in fatty acid metabolism)
Recycles S-adenosylmethionine
What in the world is SAM?
SAM (S- adenosyl methionine) donates its methyl groups to neurotransmitter and other biosynthetic pathways. Making of SAM involves Cobalamin, so if there is B12 deficiency, there might be neurological problem, amongst other reasons too that is.
T/F: methy-THF is used only in the production of SAM, and the methyl group is passed through B12. In the absences of B12, methyl-THF builds up thereby delepoing other forms of THF
True
How can excessive folate dietary intake mask a cobalamin deficiency?
when you take in a lot of supplemental B9, there will be supply of THF methyl transfers, so won’t show symptoms of megaloblastic anemia and there will be normal DNA production too, only way to tell there is a cobalamin deficiency in this instance is that there would be inadequate amount of SAM
T/F: B12 deficiency interferes with BOTH SAM production and regeneration of tetrahydrofolate
True
5-fluorouracil and methotrexate are _____ drugs, and these drugs target ______
Chemotherapeutics
DNA synthesis (5-FU targets conversion of methylene-THF to thymidine, and MTX targets formation of tetrahydrofolate)
If cancer pt has a buildup of dihydrofolate, you know that he/she is taking this drug.
Methotrexate, because methotrexate competitively inhibits dihydrofolate reductase, prevent the conversion of dihydrofolate to tetrahydrofolate
Which drug has a more specific target: 5-fluorouracil or methotrexate
5-fluorouracil, as this drug blocks thymidine synthesis only, whereas methotrexate blocks the formation of tetrahydrofolate which is the precursor to both the purine and pyrimidine biosynthesis.
