Catechol O-methyltransferase

Catechol O-methyltransferase (COMT) is an enzyme that catalyzes the O-methylation and inactivation of catecholamine neurotransmitters and catechol hormones, thereby regulating their biological half-lives (UniProt: P21964). The protein also modulates the duration of action of certain neuroactive drugs including L-DOPA and isoproterenol. COMT is expressed in human tissues and plays a critical role in dopamine and norepinephrine signaling.

In the UniProt knowledgebase, COMT is associated with schizophrenia (MIM 181500), reflecting its role in catecholamine metabolism and potential contribution to psychotic disorders (UniProt: P21964). Given the central importance of dopaminergic signaling in both neuropsychiatric and neurodegenerative contexts, dysregulation of catecholamine catabolism has broader implications for brain function.

Regarding Alzheimer's disease, COMT is upregulated in human post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of +0.49 across one subcellular fraction in TMT-labeled quantitative proteomics. This elevation may reflect altered catecholamine metabolism in the AD brain, potentially contributing to neuroinflammatory or neurodegenerative processes.