Interspecies comparison in the COMT-mediated methylation of 3-BTD

Abstract

The methylation behaviour of 3-BTD in liver S9 from eight different species was characterized with respect to the similarities and differences of their metabolic profiles, catalytic efficacy and inhibitory potency by a known chemical inhibitor.

Integrated Mass Spectrometry Reveals Celastrol As a Novel Catechol-O-methyltransferase Inhibitor

“…11−13 Unfortunately, further applications of currently available COMT inhibitors have been limited by their insufficient brain penetration or severe side effect. 14,15 Here, we applied chemical proteomics to identify COMT as a major binding target of celastrol and verified the finding with targeted mass spectrometry methods. We also analyzed the binding stoichiometry between celastrol and COMT with time isoform S-COMT and membrane-bound form MB-COMT and thus induced a significant increase of DA in neuroendocrine chromaffin cells.…”

“…In clinical practice, COMT inhibitors are used in combination with levodopa, the precursor of dopamine, to control the motor symptoms of Parkinson’s disease. COMT inhibitors have also been proposed to treat other diseases such as Alzheimer’s disease, schizophrenia, deficit hyperactivity disorder, etc. − Unfortunately, further applications of currently available COMT inhibitors have been limited by their insufficient brain penetration or severe side effect. , …”