Chemical and Biochemical Characteristics of Topa Quinone

Abstract

2,4,5-Trihydroxyphenylalanine (6-hydroxydopa, abbreviated as topa) is a perhydroxylated derivative of an amino acid, tyrosine. It rarely occurs in nature as the free amino acid, but is well known as a very strong neurotoxic agent. The neurotoxicity is ascribed mainly to its chemical reactivity and redox capacity. In addition, the oxidized form of topa, topa quinone, has been shown to be an active non-N-methyl-d-aspartate glutamatergic agonist and to produce neuronal cell death. Topa and topa quinone may be biosynthesized enzymatically and non-enzymatically from dopa or from tyrosine through dopa. On the other hand, topa quinone bound covalently in a protein has been identified in copper amine oxidase, in which topa quinone serves as an essential cofactor in catalyzing the oxidation of amines. The topa quinone cofactor is produced by post-translational modification of a specific tyrosine precursor with the participation of the enzyme-bound copper ion. These physiological and biochemical features of topa quinone as well as its chemical properties revealed by recent model studies are reviewed here. © 1997, Taylor & Francis Group, LLC. All rights reserved.