Catechol-O-methyltransferase: substrate-specificity and stereoselectivity for beta-adrenoceptor agents.

Article Details

Citation

Raxworthy MJ, Youde IR, Gulliver PA

Catechol-O-methyltransferase: substrate-specificity and stereoselectivity for beta-adrenoceptor agents.

Xenobiotica. 1986 Jan;16(1):47-52.

PubMed ID
2868577 [ View in PubMed
]
Abstract

Isoprenaline, isoetharine, rimiterol, dobutamine and nadolol were investigated as substrates for purified pig-liver catechol-O-methyltransferase using a sensitive spectrophotometric assay. Kinetic parameters, Km and Vmax, were defined and the apparent first-order rate constant (Vmax/Km) was derived. On the basis of the apparent first-order rate constant, rimiterol was found to be a 1.5-fold and dobutamine a 5-fold better substrate for catechol-O-methyltransferase than isoprenaline; isoetharine shows no improvement over isoprenaline. Nadolol is not a substrate for catechol-O-methyltransferase. O-Methylation of isoprenaline- and noradrenaline-enantiomers was found to be stereoselective: catechol-O-methyltransferase shows selectivity towards the laevo (-) isomer with respect to the (+) form or racemic mixture. The investigation indicated stereochemical and steric determinants important in the interaction of catechol-O-methyltransferase with physiologically and clinically important beta-adrenoceptor agents.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
DobutamineCatechol O-methyltransferaseProteinHumans
Unknown
Substrate
Details