Nonenzymatic conversion of 3,4-dihydroxyphenylalanine to 2,4,5-trihydroxyphenylalanine and 2,4,5-trihydroxyphenylalanine quinone in physiological solutions.

Abstract:

:2,4,5-Trihydroxyphenylalanine (TOPA) oxidizes in solution to form a quinone derivative that is a non-N-methyl-D-aspartate agonist and neurotoxin. Although pathways have been postulated for the formation of both TOPA and TOPA quinone from closely related catecholamines, the generation of these compounds has not been conclusively demonstrated by analytical techniques. Reverse-phase HPLC with a dual electrode coulometric detector was used to analyze TOPA containing solutions in an effort to rigorously characterize the behavior of this substance under physiological conditions. Electrode potential, buffer system, and methanol concentration were varied to obtain optimal conditions to selectively detect and quantify TOPA and TOPA quinone from closely related catecholamines. TOPA was shown to rapidly autoxidize to TOPA quinone by a process dependent on pH. TOPA was the dominant species at acidic pHs (below 5-6), whereas TOPA quinone was dominant at physiological pHs. This conversion was reversible upon acidification. In addition, we found that 3,4-dihydroxyphenylalanine can autoxidize to form both TOPA and TOPA quinone under physiological conditions. This partial conversion (0.5%) is time dependent and can be substantially decreased (0.2%) in acidic conditions (pH < or = 3). These results suggest that some of the excitatory and excitotoxic properties that some investigators have attributed to DOPA may actually be due to its conversion to TOPA and TOPA quinone.

journal_name

J Neurochem

authors

Newcomer TA,Palmer AM,Rosenberg PA,Aizenman E

doi

10.1111/j.1471-4159.1993.tb03602.x

subject

Has Abstract

pub_date

1993-09-01 00:00:00

pages

911-20

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

61

pub_type

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