Folate and B12 Flashcards
Folate RDA
400 mcg/day adults
600 mcg/day in pregnancy (up to 1 mg)
5-methyltetrahydrofolate = most active form
Folate absorption/availability
destroyed by heat, oxidation, light, processing approx 50% absorbed - hydrolyzed to monoglutamate by carboxypeptidase on brush border (zinc dependent) absorption inhibited by - alcohol - legumes, lentils - cabbage - oranges
Folate functions
coenzyme for transfer of one-carbon units
- nucleic acid (DNA) and AA (met, his, gly, ser) metabolism
- methylation rxns
Functions of folate-dependent methylation
gene regulation
detox
neurotransmitter synthesis and metabolism (DA and EPI)
- NE –> EPI and serotonin —> melatonin
immune cell maturation (T and NK cells)
DNA synthesis (purine ring, RBC production)
energy production (CoQ10, carnitine, creatine, ATP)
myelin production
cell membrane synthesis/maintenance (phosphatidylcholine)
Folate deficiency
incr homocysteine levels megaloblastic anemia: fatigue, weakness, SOB neural tube defects during pregnancy cognitive impairment: dementia peripheral neuropathy
Folate toxicity
none known
may mask B12 deficiency in megaloblastic anemia
MTHFR SNPs
677C>T
heterozygous = 20-50% of population
homozygous = 3-32% of pop; 65% reduction in enzyme activity
—> lower folate status, diminished methylation, incr homocysteine levels
Folate food sources
leafy greens mushrooms brassicas citrus nuts/seeds legumes enriched cereals
Cobalamin RDA
2.4 mcg/day
forms =
*adenosylcobalamin - methylmalonyl-CoA mutase
*methylcobalamin - homocysteine methyltransferase
aquocobalamin
cyanocobalamin (inactive, often supplemented, conversion to active form questionable)
Cobalamin/B12 absorption
absorb 40-89%
heat/light/oxidation stable
binds to R-protein in stomach; cleaved in SI by pancreatic enzymes
binds to IF and absorbed in the ileum via cubilin
bound to transcobalamin II in the blood
** to assess test methylmalonic acid in serum or urine**
Cobalamin/B12 storage
mostly adenosylcobalamin
approx 50% in the liver (2-4 mg)
may take 3-5 years to develop a deficiency
Methylcobalamin
Homocysteine metabolism (methionine synthase) RBC metabolism
Adenosylcobalamin
needed to convert methylmalonyl-CoA to succinyl-CoA
- methylmalonyl CoA mutase
{succinyl-CoA ===> TCA cycle/hemoglobin synthesis}
Cobalamin/B12 deficiency
megaloblastic anemia
pernicious anemia
memory loss/dementia
peripheral neuropathy
Cobalamin/B12 deficiency causes
reduced intake
hypochlorhydria/atrophic gastritis/H.pylori infx
malabsorption conditions/intestinal resection
medications: PPIs, H2 blockers, cholestryramine, metformin??
