Folate deficiency affects histone methylation.

摘要: Formaldehyde is extremely toxic reacting with proteins to crosslinks peptide chains. a metabolic product in many enzymatic reactions and the question of how these enzymes are protected from formaldehyde that generated has largely remained unanswered. Early experiments our laboratory showed two liver mitochondrial enzymes, dimethylglycine dehydrogenase (DMGDH) sarcosine (SDH) catalyze oxidative demethylation (sarcosine common name for monomethylglycine). The products were demethylated substrates formaldehyde, produced removed methyl group. Both DMGDH SDH contain FAD both have tightly bound tetrahydrofolate (THF), folate coenzyme. THF binds reversibly form 5,10-methylene-THF. At time we purified DMGDH, THF, reacted during reaction This effectively scavenged protect enzyme. Recently, post-translational modifications on histone tails been shown be responsible epigenetic regulation gene expression. One methylation lysine residues. first enzyme discovered accomplish modified histones was demethylase (LSD1). LSD1 specifically removes groups di- mono-methylated lysines at position 4 3. contained residue formaldehyde. mechanism analogous previously postulated i.e. oxidation N-methyl bond methylene imine followed by hydrolysis generate suggested might also involved scavenge produced. Our hypotheses native analogy serves class demethylases destructive effects generation formation We present pilot data showing decreased livers as result dietary deficiency associated increased levels methylated can activity resulting available active site caused deficiency. Because regulate expression this suggests may play more important role than simply serving carrier one-carbon units factor other diseases low folate.