When the DDC enzyme is inhibited, COMT enzyme activity increases1-4

The catechol-O-methyltransferase (COMT) enzyme metabolizes levodopa (L-dopa) into 3-O-methyldopa (3-OMD). But when the dopa decarboxylase (DDC) enzyme is inhibited, COMT becomes the predominant peripheral metabolic pathway, further disrupting L-dopa’s journey to the brain by metabolizing even more of it into 3-OMD.1-5

The promise of L-dopa may be at further risk because it has been shown that 3-OMD may compete for transport across the blood-brain barrier6,7

3-OMD has an affinity for the LNAA transporter and may compete with the remaining L-dopa7,8*

3-OMD has more than 3× the half-life of L-dopa9

3-OMD can reach plasma concentrations 10× higher than L-dopa3

bar1 bar2 bar3 bar4 bar5

Artistic depiction is provided for illustration purposes only and is not a representation of exact molecular mechanism.

*LNAA transporter is the large neutral amino acid transport carrier system from the gut to the circulatory system, and from circulation to the brain.8



Blood-brain barrier

When the DDC enzyme is blocked, the COMT enzyme can make L-dopa's journey to the brain more difficult1

L-dopa may be metabolized by the COMT enzyme or may compete with 3-OMD for transport across the blood-brain barrier. This may result in only a small portion of each L-dopa dose reaching the brain.1,7,10

Any interference with the ability of L-dopa to reach the brain may impact its effect.1,4 A greater knowledge of enzymatic activity can help you focus on getting the most out of L-dopa.