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21 Cards in this Set
- Front
- Back
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What are the main forms of Folate? What is active?
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Main: Pteroglutamic Acid (PteGlu)
2 x reduced: Dihydrofolic acid = H2PteGlu 4 x reduced + glutamate: diglutamyl tretrahydrofolic acid = H4PteGlu2 |
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What enzyme interchanges these forms?
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DHFR
Dihydrofolate reductase |
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What enzyme removes/adds glutamic groups?
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g-glutamyl hydrolases
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What form of folate is usually found in blood?
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MethylH4PteGlu1
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What is the sound byte of folate?
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Folate is a carrier of single carbon units involved in amino acid and nucleotide metabolism.
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What is the source of single carbon units in rxns involving folate?
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Serine (-->Glycine)
&Figlu (from Hist) --> Glu |
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Where do the single carbon units end up?
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1. Homocysteine --> Methionine
2. Pyrimidine dUMP->dTMP 3. Purine syntheses: AICAR -> fAICAR and GAR -> fGAR |
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What is reductase?
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Reductase is the enzyme that reduces 5,10 methylene H4PteGlu to 5,methyl H4PteGlu in an IRREVERSIBLE reaction
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What regulates the action of reductase?
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1. High conc. of H2PteGlu (which results from dUMP -> dTMP production)
2. High concentration of SAM |
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What is the pathway of methionine synthesis?
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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.
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What vitamins are required in met. synthesis pathway?
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RF, PLP
and B12!!!!!! For conversion of homocystein --> methionine |
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What is the Figlu amino acid path?
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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) |
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What is dUMP? dTMP?
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Involved in Pyrimidine synthesis.
deoxyuridylate deoxythymidylate |
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What is unique about the reaction of dUMP-->dTMP in regards to folate?
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The form of folate that results is H2PteGlu and it must be reduced by DHTR to be reactivated.
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What are the folate forms that purine and pyrimidine sythesis begins with?
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Pyrimidine: 5,10 methylene THF
Purine: 10 formyl-THF |
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What is the enzyme that catalyzes dUMP --> dTMP
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thymidylate synthase
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In the B12 dependent reaction of homocysteine -> methionine, what form of B12?
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methylated form. Remember, cobalt can have different ligands: CN, CH3, or adenosyl.
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What is the transmethylation cycles?
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methionine -> SAM (s-adenosyl met) --> donation of CH3 to DNA/RNA/phopholipis which forms s-adenosyl homo --> de-adenolated --> homocystein again.
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Describe folate deficiency and the methyl trap
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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.
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Why does folate deficiency results in macrocytic anemia?
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Not enough folate around for moving C-units for pyrimidine (dTMP->dUMP) synthesis and purine synthesis.
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Why does B12 deficiency results in macrocytic anemia?
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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!!!**** |
