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Regulation of Betaine Homocysteine Methyltransferase by 3',5'‐Adenosine Bisphosphate
Author(s) -
Dorosheva Oleksandra,
Spiegelberg Bryan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.884.37
Subject(s) - homocysteine , methyltransferase , regulator , chemistry , enzyme , biochemistry , betaine , allosteric regulation , methylation , dna , gene
Homocysteine (Hcy) has gained considerable interest in the clinic as a potential risk factor for inflammation and heart disease. One route of homocysteine metabolism involves the enzyme betaine‐homocysteine methyltransferase (BHMT). BHMT is reportedly inhibited by S ‐adenosyl methionine (SAM), but other in situ regulators of BHMT activity are not well characterized. We discovered that native mouse liver BHMT interacts with an intermediate in sulfur assimilation, 3',5'‐adenosine bisphosphate (PAP), suggesting the possibility that PAP is an allosteric regulator of this multimeric enzyme. The use of recombinant BHMT confirms a direct interaction between the enzyme and the nucleotide. The role of PAP as a regulator of the enzyme activity is being tested in vitro via quantitative 1 HNMR examination of BHMT metabolites in the presence of PAP and via quantification of BHMT metabolites in cells treated with lithium, a specific inhibitor of PAP catabolism.