Coenzyme: prosthetic group cofactor derived from a 'B' vitamin (usually)
Why are alcoholics deficient in folate?
Alcohol causes problems with the absorption of folate.
Which is the vitamin and which is the coenzyme of folate and tetrahydrofolate (THF)?
Folate is the vitamin, THF is the coenzyme
What 3 metabolic products is folate involved in producing?
1. dTMP (for DNA synthesis)
2. Purines
3. methionine (by donating a methyl group to homo-cysteine with B12)
True or false: Tetrahydrofolate (THF) is recycled in the cell under normal conditions.
True
True or false: THF exists in only one form in the cell.
False - tetrahydrofolate exists in many forms in the cell
True or false: Folate donates methyl groups in the production of methionine.
True
How does folate deficiency lead to anemia?
Leads to megaloblastic anemia because there isn't enough folate available for DNA synthesis. Because cells in the BM are produced so rapidly, they have a high DNA production requirement.
Explain how methotrexate inhibits DNA synthesis.
Methotrexate is a folic acid analog, so it replaces folic acid in reactions and prevents them from occurring.
How do solfonamides kill bacteria?
They mimic PABA, preventing bacteria from making folic acid.
How does folate relate to epigenetics?
Folate can mediate the methylation of DNA in CpG regions. Methylation of CpG regions silences the gene.
True or false: folate has no effect on neural tube defects.
False: folate supplements can help prevent neural tube defects in a developing fetus.
What is S-Adenosyl methionine (SAM) and how is it related to folate?
SAM is involved in methyl group transfers. Folate, in the form of 5-methyl-THF, is involved in the production of SAM.
How is S-Adenosyl methionine linked to colorectal cancer?
A lack of folate may lead to a decrease in SAM, resulting in DNA hypomethylation and colorectal cancer.
True or false: we have a very high daily requirement for vitamin B12.
False - a very low daily requirement
What is a main source of vitamin B12 and where is it stored?
Common source: animal food products (so vegans at risk of deficiency). Stored in the liver.
What is pernicious anemia and how is it caused?
It is a megaloblastic anemia resulting from poor B12 absorption. This may be caused by autoimmune destruction of parietal cells or IF (a factor secreted to help with the absorption of B12).
What are the 2 reactions that vitamin B12 is involved in?
Methionine synthase: homocysteine -> methionine (also using folate)
Methylmalonyl CoA mutase: methylmalonyl CoA -> succinyl CoA (which then enters the TCA)
How does B12 deficiency cause megaloblastic anemia?
By causing cells to be deficient in some THF forms. The anemia is caused by a lack of methylene-THF for the tymidylate synthase reaction: Hcy + 5-methyl THF -> Met + THF in the presence of B12. Thus, without B12, you get +5-methyl-THF and -THF.
What is the "folate trap?"
Vitamin B12 deficiency may also cause folate deficiency because vitamin B12 is required to recycle folate. You cannot re-synthesize THF from 5-methyl-THF as you normally would so there is a decrease in THF and an increase in 5-methyl-THF in vit. B12 deficiency. You treat folate deficiency by also giving vitamin B12.
True or false: vitamin B12 deficiency leads to a decrease in methionine, and increase in homocysteine, and an increase in methylmalonyl CoA (MMA).
True
How does B12 deficiency lead to nerve damage?
It results in a decrease in methionine, which decreases methylation. Nerves are sensitive to a decrease in methylation. Increases in homocysteine and MMA may also be toxic to neurons.
True or false: Neurological changes due to vitamin B12 are always reversible.
False, they may be irreversible. Thus, always treat folic acid anemia with vitamin B12 as well, since the folic acid anemia may be caused by the "folate trap", resulting from vit. B12 deficiency.
