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 microdialysis. In the brain L-threo-DOPS was metabolized by 3 different enzymes; aromatic L-amino acid decarboxylase, catechol-O-methyltransferase, and DOPS-aldolase. DOPS-aldolase was the main enzyme which metabolizes L-threo-DOPS. The amounts of the metabolites by L-amino acid decarboxylase (norepinephrine and its metabolites) were 0.4% of the total amounts of metabolites detected in the dialysate, while those by catechol-O-methyltransferase, 2.1 %, and by DOPS-aldolase, 97.5%, after 100 min perfusion of L-threo-DOPS. L-threo-DOPS was found to increase extracellular levels of dopamine and serotonin, and to inhibit monoamine catabolism in the brain. Inhibition of DOPS-aldolase should improve its effectiveness as the supplement therapy of norepinephrine.