Green tea polyphenols: novel irreversible inhibitors of dopa decarboxylase.
The green tea gallocatechins, (-)-epigallocatechin-3-O-gallate (EGCG), and (-)-epigallocatechin (EGC) were found to be inhibitors of Dopa decarboxylase (DDC). EGCG and EGC inactivate the enzyme in both a time- and concentration-dependent manner and exhibit saturation of the rate of inactivation at high concentrations, with efficiency of inactivation values (k(inact)/K(i)) of 868 and 1511 M(-1) min(-1), respectively. In contrast, gallic acid behaves as a weak inhibitor of DDC. Protection against inactivation by EGCG and EGC was observed in the presence of the active site-directed inhibitor D-Dopa. Either EGCG or EGC induce changes in the absorbance and CD bands of the visible spectrum of enzyme-bound PLP. Taken together, these findings indicate the active site nature of the interaction of DDC with both polyphenols. On the basis of the properties of the EGCG-inactivated enzyme, it can be suggested that inactivation could be ascribed to a covalent modification of not yet identified residue(s) of the active site of DDC.
Bertoldi
M
M
Dipartimento di Scienze Neurologiche e della Visione, Sezione di Chimica Biologica, Facoltà di Medicina e Chirurgia, Università degli Studi di Verona, Strada Le Grazie, 8, Verona, 37134, Italy.
Gonsalvi
M
M
Voltattorni
C B
CB
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001665:Binding Sites / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004296:Dopa Decarboxylase / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D013053:Spectrophotometry; D013552:Swine; D013662:Tea / Q000737:chemistry*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D004296:Dopa Decarboxylase; C057580:gallocatechol