Catechol O-Methyltransferase

Supporting information

Catechol O-Methyltransferase (COMT) (EC catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to a catechol substrate in the presence of magnesium (Mg2+) ions. COMT substrates include dopamine, norepinephrine, epinephrine and levodopa. There are two isoforms of COMT: soluble (S-) COMT and membrane-bound (MB-) COMT.

COMT is ubiquitously expressed, with the highest COMT activity occurring in the liver and kidneys. Notable expression of COMT occurs in kidney proximal tubular epithelial cells, where the enzyme is thought to indirectly regulate the metabolism of dopamine and other catecholamines. However, a significant focus of research has been the involvement of COMT in the adverse effects associated with the use of levodopa for Parkinson's disease (PD) therapy.

Prior to reaching the brain, orally administered levodopa can be metabolized in peripheral tissues by either COMT or L-amino acid decarboxylase (AADC). Metabolism of levodopa by COMT produces 3-O-methyldopa, a metabolite with no therapeutic effect in PD and that competes with levodopa for transport into the brain, thereby attenuating the therapeutic benefit of levodopa. This effect is thought to underlie the "wearing off" phenomenon associated with levodopa treatment; a phenomenon that is characterized by motor fluctuations or dyskinesias in PD patients following long-term levodopa treatment. Thus, inhibiting peripheral COMT improves the bioavailability of levodopa in the brain and decreases the "wearing off" phenomenon.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Catechol O-Methyltransferase Human COMT NM_000754 P21964
Mouse Comt NM_007744 O88587
Rat Comt NM_012531 P22734

Literature for Catechol O-Methyltransferase

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Parkinson's Life Science Poster

Written by Anthony H.V. Schapira

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