folate metabolism
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Introduction
Metabolism of folate centers about tetrahydrofolate which is involved two different metabolic pathways:
Tetrahydrofolate (THF) is an activated carrier of one carbon units.
Other carriers included S-adenosylmethionine (SAM, a carrier of -CH3) & biotin (a carrier of -CO2).
The carbon carried by THF is bound to N5 or N10 of THF or both.
The most reduced form carries a -CH3 group; the intermediate form carries a methylene group; the most oxidized forms carry a methenyl, formyl or formino group.
The one carbon units carried by THF are interconvertible.
The THF derivatives serve as methyl donors in a variety of biosyntheses:
- N5-methyl-THF -> homocysteine to methionine
- N5,N10-methylene-THF -> dUMP to dTMP & in glycine biosynthesis
- N10-formyl-THF -> biosynthesis of purines
Biochemistry
- methionine metabolism 5
- enzyme methionine synthase
- substrate homocysteine + 5-methyltetrahydrofolate
- product methionine + tetrahydrofolate
- methionine metabolism 6
- methionine metabolism 7
- folate metabolism 1
- enzyme: thymidylate synthase
- substrate: deoxyuridine monophosphate + N5,N10-methylene tetrahydrofolate
- product: thymidine monophosphate + dihydrofolate
- generation of thymidylate for DNA synthesis
- folate metabolism 2
- enzyme: dihydrofolate reductase
- substrate: dihydrofolate + NADPH + H+
- product: tetrahydrofolate + NADP+
- regeneration of tetrahydrofolate using reducing equivalents from NADPH
- folate metabolism 3
- enzyme: amine oxidoreductase
- substrate: folate + NADPH + H+
- product: dihydrofolate + NADP+)
- folate metabolism 4
- enzyme: transferase
- substrate: tetrahydrofolate + formate + ATP
- product: N10-formyl tetrahydrofolate + ADP
- folate metabolism 5
- enzyme: isomerase
- substrate: N10-formyl tetrahydrofolate
- product: N5-formyl tetrahydrofolate
- folate metabolism 6
- enzyme: dehydrogenase
- substrate: N5,N10-methylene tetrahydrofolate + NADP+
- product: N5,N10-methenyl tetrahydrofolate + NADPH + H+
- folate metabolism 7
- enzyme: hydrolase
- substrate: N5,N10-methenyl tetrahydrofolate + ADP + H2O
- product: N10-formyl tetrahydrofolate + ATP
- folate metabolism 8
- enzyme:bstrate aminotransferase
- substrate: N5,N10-methenyl tetrahydrofolate + NH3
- product: N5-formimino tetrahydrofolate
More general terms
Additional terms
References
- ↑ Stryer Biochemistry WH Freeman & Co, New York, 1988 pg 580, 614