B12 and folate Flashcards
how is B12 absorbed?
R-binders bind B12 in the stomach and protect it from acid, in the duodenum, R-binders are degraded and B12 is freed. Intrinsic factor (synthesized by parietal cells) will bind to free B12 in SI and carry it to receptors in the ileum
what are the 2 enzymes that are dependent on B12?
1- methyl-malonyl-CoA mutase
2- MTHMT
what happens in b12 def to methyl-Malonyl-CoA mutase?
unable to convert methyl-malonyl CoA to succinyl-CoA, methyl-malonyl-CoA will accumulate in blood and becomes incorporated into phospholipids, leading to neurologic damage
what happens in B12 def to MTHMT?
unable to convert homocysteine –> methionine, homocysteine will accumulate and decreased met/SAM, neurologic consequences
how is folate absorbed?
folate conjugase (in the brush border) will hydrolyze polyglutamate forms down to PteGlu1 = folic acid, which is absorbed into the enterocyte, while inside the enterocyte, dihydrofolate reductase will acts of folic acid x 2 to form THF
what is the central folate intermediate?
THF
what is the major circulatory form of folate?
5-methyl-THF
what is the methyl-folate trap?
when B12 is deficient, folate becomes “trapped” in 5-methyl-THF form and cannot be recycled back to THF. This can be overcome with folate supplementation
what will be present in blood in 2* folate def, but not 1* folate def?
2* is due to B12 def, so will have high methyl-malonyl-CoA, low succinyl-CoA and high homocysteine as well as low THF
what happens to glycine if THF levels are low?
THF is required for the glycine cleavage complex to function, if THF is low then glycine will accumulate, leading to glycine encephalopathy
MOA of trimethoprim
inhibits bacterial dihydrofolate reductase, unable to form THF
MOA of sulfonamides
inhibit pteridine sythetase in bacteria, unable to form folate
MOA of methotrexate
inhibits human dihydrofolate reductase, unable to form THF, therefore can’t effectively replicate cells
