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21 Cards in this Set

  • Front
  • Back
What are the main forms of Folate? What is active?
Main: Pteroglutamic Acid (PteGlu)

2 x reduced: Dihydrofolic acid = H2PteGlu
4 x reduced + glutamate:
diglutamyl tretrahydrofolic acid = H4PteGlu2
What enzyme interchanges these forms?
Dihydrofolate reductase
What enzyme removes/adds glutamic groups?
g-glutamyl hydrolases
What form of folate is usually found in blood?
What is the sound byte of folate?
Folate is a carrier of single carbon units involved in amino acid and nucleotide metabolism.
What is the source of single carbon units in rxns involving folate?
Serine (-->Glycine)
&Figlu (from Hist) --> Glu
Where do the single carbon units end up?
1. Homocysteine --> Methionine
2. Pyrimidine dUMP->dTMP
3. Purine syntheses: AICAR -> fAICAR and GAR -> fGAR
What is reductase?
Reductase is the enzyme that reduces 5,10 methylene H4PteGlu to 5,methyl H4PteGlu in an IRREVERSIBLE reaction
What regulates the action of reductase?
1. High conc. of H2PteGlu (which results from dUMP -> dTMP production)
2. High concentration of SAM
What is the pathway of methionine synthesis?
Starts w/H4PteGlu-->5,10 methylene THF (addition of C-group from serine) /serine becomes glycine enz=Ser OH-CH3 transferase/ reduction of methyleneTHF -> 5-methyl THF w/reductase (irreversible); then c-unit transfered from homosysteine --> methionine "met syntase". THF reformed.
What vitamins are required in met. synthesis pathway?
and B12!!!!!! For conversion of homocystein --> methionine
What is the Figlu amino acid path?
1st step THF obtains c-group from Figlu in the form of a formimino group. Enzyme = formimino transferase. "formimino". THF becomes 5-formimino THF. Then it loses NH3 group to become 5,10methenyl THF. Enzyme = cyclodeaminase.

Then it can go onto either the right (purine synthesis) or the left (meth. synthesis or pyrimidine)
What is dUMP? dTMP?
Involved in Pyrimidine synthesis.
What is unique about the reaction of dUMP-->dTMP in regards to folate?
The form of folate that results is H2PteGlu and it must be reduced by DHTR to be reactivated.
What are the folate forms that purine and pyrimidine sythesis begins with?
Pyrimidine: 5,10 methylene THF

Purine: 10 formyl-THF
What is the enzyme that catalyzes dUMP --> dTMP
thymidylate synthase
In the B12 dependent reaction of homocysteine -> methionine, what form of B12?
methylated form. Remember, cobalt can have different ligands: CN, CH3, or adenosyl.
What is the transmethylation cycles?
methionine -> SAM (s-adenosyl met) --> donation of CH3 to DNA/RNA/phopholipis which forms s-adenosyl homo --> de-adenolated --> homocystein again.
Describe folate deficiency and the methyl trap
If someone is deficient on folate, the reaction of homocysteine-> met cannot occur. CH3-THF builds up since the rxn that formed it from methylene-THF is irreversible. The methyl groups essentially get trapped.
Why does folate deficiency results in macrocytic anemia?
Not enough folate around for moving C-units for pyrimidine (dTMP->dUMP) synthesis and purine synthesis.
Why does B12 deficiency results in macrocytic anemia?
B12 catalyzes homocysteine->methionine w/enzyme "met. synthase"

Because it also causes a methyl trap which RESULTS in there being not enough folate around for pyrimidine (dTMP->dUMP) synthesis and purine synthesis.

*****WITH A b12 deficiency you INDUCE a FOLATE deficiency!!!****