PubMed · 5008563
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1972-02-17. Gout and levodopa.. https://doi.org/10.1056/nejm197202172860718
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We have determined the kinetic parameters for Dopa decarboxylase (DDC) of three ring-fluorinated analogs of 3,4-dihydroxyphenylalanine (Dopa). The rank order of catalytic efficiency of decarboxylation (k(cat)/K(m)) is Dopa>6-F-Dopa>2-F-Dopa>5-F-Dopa. This rank is consistent with previous in vivo and in vitro studies which indicate that, of the fluorinated analogs, 6-F-Dopa has pharmacokinetics that are most suited for positron emission tomographic (PET) evaluation of dopamine function. The effectiveness of PET as a diagnostic tool, the convenient half-life of (18)F (110 min) and the favorable pharmacokinetics of 6-[(18)F]FDOPA have combined to make this an extremely valuable reagent to study dopaminergic activity. The reactions of the related fluorinated DOPS analogs show that, while 6-F-threo-3,4-(dihydroxyphenyl)serine (DOPS) is decarboxylated at approximately the same rate as the non-fluorinated substrate, 2-F-threo-DOPS is not converted into the corresponding amine. In both cases a Pictet-Spengler condensation with the pyridoxal 5(')-phosphate (PLP) cofactor occurs to produce tetrahydroisoquinolines. Condensation of fluorinated catecholamines and catechol amino acids with endogenous aldehydes will be investigated as an approach to study possible mechanisms of L-Dopa-linked neurotoxicity.
One main metabolizing pathway of levodopa is O-methylation to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). Since COMT requires Mg2+ and S-adenosylmethionine as methyl donor for this transmethylating process, COMT converts S-adenosylmethionine to S-adenosylhomocysteine and subsequent homocysteine. Objective of this study was to demonstrate relations between plasma levodopa, 3-OMD and total homocysteine in treated parkinsonian subjects. We measured homocysteine, levodopa and 3-OMD by HPLC. We compared plasma homocysteine in two groups of treated parkinsonian subjects subdivided according to their 3-OMD level. Homocysteine was significantly (p = 0.002) elevated in the group with higher 3-OMD concentrations and positively (r = 0.52, p = 0.0006) correlated to 3-OMD. Homocysteine induces vascular disease. Previous studies showed an increase of ischaemic heart- and cerebrovascular disease in treated parkinsonian patients.
The photoconductivity effect in synthetic dopa-melanin polymer with relation to the charge hopping conduction has been investigated. Measurements of the rise and decay of photocurrents upon visible radiation (400-800 nm) and at temperatures of 293-326 K allowed the determination of the major trapping levels as follows: 56, 35 and 26 kJ/mol. Spectral response of the steady-state photocurrent in the range 367-1100 nm showed significant departures from the absorption spectrum of melanin. The high concentration of traps or recombination centers can explain the long time-constants calculated from the photocurrent rise and decay curves. The results obtained can support the postulated earlier polarons and hopping model of conductivity in synthetic dopa-melanin.