lecture 12: folate

Question 1

folate

Answer 1

water-soluble B vitamin (B9)
ability to donate and accept one-carbon moieties > nucleotide synthesis, re-methylation of homocysteine to methionine

Question 2

folate metabolism

Answer 2

reduction of pyrazine ring to THF, elongation of glutamate chain, acquisition and oxidation or reduction of 1C units

Question 3

predominate form of folate in blood circulation

Answer 3

5-methyl-THF

Question 4

polyglutamates

Answer 4

5-8 glutamate chains, increased affinities for folate-dependent enzymes

Question 5

FPG synthetase

Answer 5

conversion of folate to polyglutamate form

Question 6

folate coenzymes

Answer 6

act as acceptors or donors of 1C units
utilized in methionine, thymidylate, purine synthesis

Question 7

C1 THF synthase

Answer 7

interconversion of folate coenzymes

Question 8

purine cycle

Answer 8

THF enters purine cycle when formylated (10-Formyl-THF)

10-Formyl-THF can be used to produce purines in a two-step process.
10-Formyl-THF can also be used to produce 5,10-methylene-THF through the actions of C1-THF synthase.
The enzymatic activities of C1-THF-synthase are bidirectional.

Question 9

C1-THF-synthase

Answer 9

enable reversible interconversions between 10-formyl-THF and 5,10-methylene-THF

Question 10

If folate is involved in purine synthesis, which active vitamin(s) cofactor/substrate is/are dependent upon folate?

Answer 10

riboflavin??

Question 11

thymidylate cycle

Answer 11

5,10-methylene-THF required for synthesis of pyrimidine thymidine
dUMP to dTMP

Question 12

DHF reductase

Answer 12

DHF (inactive) reduced back to THF

Question 13

cSHMT

Answer 13

serine acts as a carbon donor, converted to glycine in process, converted directly to 5,10-methylene form

Answer 14

THF is a carbon-carrier. The carbon is in the methylene form, and is donated to uridine to form thymidine. THF is oxidized to DHF in the process, and must be reduced to reform THF. THF can then either be charged with a new carbon (donated by serine), or 5,10-methylene-THF can be provided by the purine cycle.

Question 15

megaloblastic anemia

Answer 15

enlarged RBCs due to defective thymidylate synthesis coupled with enlarged dUTP pool - uracil misincorporation into DNA

Question 16

methionine/methyl cycle

Answer 16

reduction of 5,10-methylene THF to 5-methyl-THF (predominant form in circulation)
catalyzed by MTHFR (FLAVOPROTEIN - dependent on riboflavin)

Question 17

homocysteine

Answer 17

only generated from metabolism of methionine
to regenerate - folate-dependent methionine synthase rxn

Question 18

folate insufficiency

Answer 18

usually dietary insufficiency
defects in DNA synthesis - particularly in fast growing tissues

increase risk for vascular disease - high circulating homocysteine levels

increased risk for certain cancers

Question 19

folate sources

Answer 19

synthesized by microorganisms and plants
folic acid in diet in foods fortified with folic acid
vitamin supplements