The inhibition of catechol-O-methyltransferase by 2,3-dihydroxypyridine

Despite its structural similarity to catechol, 2,3-dihydroxypyridine is not a substrate but a “dead-end” inhibitor of purified pig liver catechol-O-methyltransferase. It inhibits the methylation of 3,4-dihydroxyphenylacetic acid competitively with an inhibitor constant of 15 μM. Against the methyl donor, $\text{S-}\text{adenosyl}\text{-}\text{l}\text{-}\text{methionine}$, it is an uncompetitive inhibitor (K′_i = 85 μM). Clearly, although 2,3-dihydroxypyridine interacts with the catechol-binding site of the enzyme, the presence of a nitrogen in the ring alters its susceptibility to O-methylation.