A NEW METABOLIC PATHWAY OF L-THREO-3,4-DIHYDROXYPHENYLSERINE, A PRECURSOR AMINO-ACID OF NOREPINEPHRINE, IN THE BRAIN STUDIES BY IN-VIVO MICRODIALYSIS

The metabolism and the effects of L-threo-3,4-dihydroxyphenylserine (L -threo-DOPS) were studied in the rat brain striatum by in vivo microdi alysis. In the brain L-threo-DOPS was metabolized by 3 different enzym es; aromatic L-amino acid decarboxylase, catechol-O-methyltransferase, and DOPS-aldolase. DOPS-aldolase was the main enzyme which metabolize s L-threo-DOPS. The amounts of the metabolites by L-amino acid decarbo xylase (norepinephrine and its metabolites) were 0.4% of the total amo unts of metabolites detected in the dialysate, while those by catechol -O-methyltransferase, 2.1 %, and by DOPS-aldolase, 97.5%, after 100 mi n perfusion of L-threo-DOPS. L-threo-DOPS was found to increase extrac ellular levels of dopamine and serotonin, and to inhibit monoamine cat abolism in the brain. Inhibition of DOPS-aldolase should improve its e ffectiveness as the supplement therapy of norepinephrine.