1.Enzymic sulphation of dopa and tyrosine isomers by HepG2 human hepatoma cells: stereoselectivity and stimulation by Mn2+.
Suiko M1, Sakakibara Y, Nakajima H, Sakaida H, Liu MC. Biochem J. 1996 Feb 15;314 ( Pt 1):151-8.
HepG2 human hepatoma cells, labelled with [35S]sulphate in media containing L-3,4-dihydroxyphenylalanine (L-dopa), (D-dopa), DL-m-tyrosine or D-p-tyrosine, were found to produce the [35S]sulphated forms of these compounds. Addition to the labelling media of m-hydroxybenzylhydrazine, an aromatic amino acid decarboxylase inhibitor, greatly enhanced the production of L-dopa O-[35S]sulphate and DL-m-tyrosine O-[35S]sulphate, with a concomitant decrease in the formation of dopamine O-[35S]sulphate and m-tyramine O-[35S]sulphate. With 3'-phosphoadenosine 5'-phospho[35S]sulphate as the sulphate donor., HepG2-cell cytosol was shown to contain enzymic activity catalysing the sulphation of L-dopa, D-dopa, L-m-tyrosine, D-m-tyrosine, L-p-tyrosine and D-p-tyrosine. The pH optimum of the enzyme, designated dopa/tyrosine sulphotransferase, was determined to be 8.75 with D-m-tyrosine as the substrate. The enzyme exhibited stereoselectivity for the D-form of dopa or tyrosine isomers.
2.Studies on the depletion of brain amines by m-tyrosine.
Smyth RG, Tong JH, D'Iorio A. Eur J Pharmacol. 1977 Apr 7;42(3):267-73.
The biochemical basis of the well-known physiological and pharmacological actions of m-tyrosine was examined by a detailed study of its effect on the brain biogenic amines. m-Tyrosine was injected i.p. and rat brain monoamine levels were measured. Endogenous levels of dopamine, norepinephrine and serotonin all showed approximately 50% reductions 1 h after the administration of L-m-tyrosine at 150 mg/kg. These actions of L-m-tyrosine could be blocked by the inhibition of the central dopa decarboxylase. Depletion of brain monoamines was also observed with the D-isomer of m-tyrosine, although this effect was less pronounced than that of the L-isomer. In vitro experiments with rat brain homogenates showed that L-m-tyrosine, m-tyramine and m-octopamine enhanced in efflux of exogenous labeled monamines from brain particles, whereas D-m-tyrosine was completely ineffective. From these results it is concluded that the observed decreased in brain monamine levels by L-m-tyrosine may be due to a m-tyramine-enhanced release of the amines which are quickly metabolized in vivo.
3.Inhibition of pig kidney L-aromatic amino acid decarboxylase by 2,3-methano-m-tyrosines.
Ahmad S1, Phillips RS, Stammer CH. J Med Chem. 1992 Apr 17;35(8):1410-7.
Both racemic (E)- and (Z)-2,3-methano-m-tyrosines (9E and 9Z) have been synthesized from a common intermediate, monoester (Z)-1-(ethoxycarbonyl)-2-[3-[(2-methoxyethoxy)methoxy]phenyl] cyclopropanecarboxylic acid (5). Quinine and ephedrine, respectively, were used to resolve their N-tert-butoxycarbonyl (Boc) derivatives. Among the compounds prepared, the (+)-(E)-diastereomer of 9 is the most potent inhibitor of L-aromatic amino acid decarboxylase (Dopa decarboxylase), having a Ki of 22 microM, with the (-)-Z-diastereomer (9Z) second at Ki = 49 microM. (+)-9E is a 45-fold more potent inhibitor of DDC than its acyclic analogue, D-m-tyrosine.
