COMT Human

Catechol-O-Methyltransferase (COMT) is an enzyme that plays a crucial role in the metabolism of catecholamines, which include neurotransmitters such as dopamine, epinephrine, and norepinephrine . The enzyme is responsible for the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to the hydroxyl groups of catechol substrates, a process known as O-methylation .

There are two main forms of COMT: soluble (S-COMT) and membrane-bound (MB-COMT). Both forms are encoded by a single COMT gene but differ in their structure and location within the cell . S-COMT is found in the cytoplasm and nucleus, while MB-COMT is associated with intracellular membranes .

Recombinant COMT refers to the enzyme produced through recombinant DNA technology, which involves inserting the COMT gene into a host organism to produce the enzyme in large quantities. This method allows for the production of both S-COMT and MB-COMT in various host systems, including Escherichia coli and insect cells .

COMT has been extensively studied due to its role in the metabolism of neurotransmitters and its implications in various neurological and psychiatric disorders. For instance, COMT polymorphisms have been linked to conditions such as Parkinson’s disease, schizophrenia, and depression . Inhibition of COMT is a therapeutic strategy used in the treatment of Parkinson’s disease to improve the pharmacokinetics of L-DOPA, a precursor to dopamine .

The production of recombinant COMT involves optimizing various parameters to achieve high yields and activity. For example, the use of Pichia pastoris as a host organism has been explored for the biosynthesis of membrane-bound COMT. Optimization of factors such as temperature, methanol flow-rate, and the addition of chemical chaperones like dimethylsulfoxide (DMSO) has been shown to significantly improve the specific activity of the enzyme .