What is it about?
Betaine homocysteine methyltransferase locates both to the cytoplasm and the cell nucleus. During acute liver injury BHMT accumulates in the nucleus while reducing its levels in the cytoplasm. This change of subcellular localization is due to the reduced GSH/GSSG ratio in treated cells (D-galactosamine, paracetamol/acetaminophen, buthionine sulfoximine) and addition of N-acetylcysteine prevents this anomalous distribution. Moreover, basic residues in the N-terminal of BHMT are involved in the regulation of subcellular localization. Nuclear BHMT is an active homotetramer in normal and galactosamine treated livers, but not in paracetamol-treated livers. Changes in nuclear BHMT activity correlate with the global protein homocysteinylation detected in this compartment, thus supporting the role of nuclear BHMT in the remethylation of homocysteine.
Why is it important?
This is the first report on homocysteine remethylation in the nucleus, further supporting the existence of a nuclear branch of the methionine cycle that supports epigenetic modifications.
The following have contributed to this page: Dr María A Pajares