Vitamin B12 and Folic Acid Flashcards
Another name for vitamin B12
cobalamin
what does the structure of B12 contain
Co and corrin ring system
sources of B12
meats, shellfish, poultry, eggs, diary products, NOT IN PLANTS
active forms of cobalamin
5 deoxyadenosylcobalamin and methyl cobalamin
what reactions/enzymes require B12
homocysteine N-methyltransferase (Homocysteine –> Met)
and isomerization of methyl malonyl CoA (breakdown of odd chain FA and metabolism of BCAA)
required to go from Met to Homocysteine
SAM for methylation reactions
other examples where SAM is needed:
Norepinephrine –> epinephrine
PE –> PC
m-RNA methylation
To resynthesize methionine from homocysteine, what is required
Vit B12 and THF (tetrahydrofolate)
what happens if deficiency in B12 in the Met-Cys cycle
build up of homocysteine and trapping of THF in methyl THF form
Trapping of THF in its methyl THF form causes what…?
decrease of formation of other THF derivatives and impairs nucleotide synthesis as well as DNA and RNA synthesis
what leads to homocysteinemia/homocystinuria
deficiency in B6 – needed for cystathione synthetase and cystathionase
deficiency in B9 (THF) - needed for homocysteine N-methyltransferase
deficiency in B12 - needed for homocysteine N-methyltransferase
what happens in oxidation of odd chain FA if you have a deficiency in B12
you have a build up of methylmalonyl CoA (methylmalonyl CoA mutase needs B12) which as it accumulates turns to methylmalonyl acid —> methylmalonyl aciduria
AA that form propionyl CoA
Met, Val, Ile, Thr
propionyl coA –> succinyl CoA
effects of deficiency of B12
accumulation of abnormal FA –> neurological CNS effects
what condition arises from the inability to absorb B12
pernicious anemia (NOT B12 deficiency) – have no intrinsic factor because of autoimmune destruction of parietal cells
how do you treat pernicious anemia
lifetime intramuscular injection of cyanocobalamin (skips the absorption step)
homocysteinemia as a result of B12 and THF deficiency can lead to…?
damage blood vessels –> thrombosis
lipid oxidation and increased platelet aggregation –> fibrosis and calcification of atherosclerotic plaques
causes of B12 deficiency
pure vegan diet
chronic pancreatitis
terminal ileal disease
what is megaloblastic anemia and how is it treated?
blood disorder with large red blood cells as a result of B12 or folic acid deficiency
treated with both folate(B9) and vit B12
hyperhomocysteinemia is a deficiency in what
cystatione beta synthase
manifestations of hyperhomocysteinemia
lens dislocation after age 3
osteoporosis
childhood mental retartdation
lipid deposits of atheromas
fate of cysteine after the met-cys cycle
metabolized by cysteine dioxygenase to product taurine (impo for bile salt synthesis)
produce sulfate which can be excreted in urine or using ATP can form PAPs (imp for glycolipid and GAG synthesis)
sources of folic acid (B9)
green leafy vegetables, liver, lima beans, whole-grain cereals
what is the active form of folic acid and its importance
active form of folic acid is THF (tetrahydrofolate) and it is impo to make the other many diff form of THF which is needed for a plethora of things
what are the THF derivates impo for?
DNA and RNA synthesis (purines and thymidines), some AA metabolism, synthesis of Met from homocysteine, degradation of histidine
how do you go from folic acid to its active form THF
it is a 2 step reaction using dihydrofolate reductase and 2 NADPH
PS: you get folic acid from your diet but body must undergo above process in order to get the active form
folic acid deficiency is seen in what condition
spina bifida (incomplete closures of neural tube)
in microorganisms, what enzyme is inhibited in the THF formation in treatments of cancer or bacterial infection
dihydropteroate synthetase
what competitively inhibits dihydropteroase synthetase and its importance
sulfonamides hence preventing formation of THF so no amino acid synthesis, purine synthesis, or thymidine monophosphate synthesis
PS microorganisms make their own folic acid while humans have to eat it in their diet
in human, what enzyme is inhibited in THF formation in order to treat cancer or bacterial infection
dihydrofolate reductase
what is the competitive inhibitor of dihydrofolate reductase
methotrexate
Going from Ser to Gly requires what
THF and serine hydroxymethyltransferase
Steps from Histidine to Glu
Histidine (deaminated) –> N-formiminoglutamate (FlGlu) (formimino group donated to THF) –> Glu
what happens with degradation of histidine if there is a deficiency in THF
build up of FlGlu (FlGlu in urine shows deficiency in folic acid B9)
histidinemia is a result of
histidinase deficiency
folate deficiency is caused by
methotrexate (chemotherapeutic drug), alcohol, and sulfa drugs
folic acid deficiency is most common in what population
preggo women and those leaning on that E&J
deficiency in folic acid results in?
homocytinuria and megaloblastic anemia
