One Carbon Metabolism Flashcards
what is the active form of folic acid in humans? what does it do?
tetrahydrofolic acid (THF). it is an important coenzyme in many rxns
how is THF synthesized
ingested folic acid is converted to THF via dihydrofolate reductase
what is the major source of 1-C units in most cells? minor sources?
serine is synthesized from 3-phosphoglycerate (glycolysis intermediate). the side chain B-carbon is transferred to THF by hydroxymethyltransferase
degradation of histidine can also provide 1-C units to THF
describe the different oxidative states of THF
enzymes regulate the various oxidative states of THF
the methyl state is the most reduced and used for methionine synthesis
the methylene state is an intermediate state and used for thymidylate synthesis
the formyl oxidation is the most oxidized and is for de novo purine synthesis
describe the conversion of 5,10 methylene THF to 5-methyl THF
conversion is mediated by 5,10 methylene-THF reductase and is not reversible
describe the rxn that generates methionine
5-methyl-THF methylates homocysteine to generate methionine. catalyzed by methyltransferase and requires vitamin b12
SAM
S-adenosylmethionine
methionine is converted to SAM via SAM synthase in an ATP dependent rxn. SAM is a methyl group donor used to methylate compounds
the rxn is irreversible. after SAM has donated its methyl, it is hydrolyzed back to adenosine and homocysteine
give some examples of SAM dependent methylation
used in the synthesis of creatine, carnitine, epinephrine, choline
describe the synthesis of phosphatidylcholine
requires 3 SAM dependent methylations
1 decarboxylase
3 n-methyltransferases
folate trap hypothesis
in b12 deficiency, vitamin b12 cannot catalyze the conversion of homocysteine to methionine, leaving N5-methyl-THF to accumulate
thus cellular THF is depleted
megaloblastic anemia
a defect in DNA synthesis in rapidly dividing cells d/t defects in either vitamin b12 or folic acid.
may present as slow onset anemia or neurological abnormalities
