Document Detail

Redox reaction between amino-(3,4-dihydroxyphenyl)methyl phosphonic acid and dopaquinone is responsible for the apparent inhibitory effect on tyrosinase.
MedLine Citation:
PMID:  12180986     Owner:  NLM     Status:  MEDLINE    
Amino-(3,4-dihydroxyphenyl)methyl phosphonic acid, the phosphonic analog of 3,4-dihydroxyphenylglycine, had been previously reported as a potent inhibitor of tyrosinase. The mechanism of the apparent enzyme inhibition by this compound has now been established. Amino-(3,4-dihydroxyphenyl)methyl phosphonic acid turned out to be a substrate and was oxidized to o-quinone, which evolved to a final product identified as 3,4-dihydroxybenzaldehyde, the same as for 3,4-dihydroxyphenylglycine. Monohydroxylated compounds (amino-(3-hydroxyphenyl)methyl phosphonic acid and amino-(4-hydroxyphenyl)methyl phosphonic acid) were not oxidized, neither was 4-hydroxy-l-phenylglycine. However, the relatively high Km for amino-(3,4-dihydroxyphenyl)methyl phosphonic acid (0.52 mm) indicated that competitive inhibition could not entirely explain the previously reported strong inhibitory effect (Ki = 50 and 97 micro m for tyrosine and 3-(3,4-dihydroxyphenyl)alanine (Dopa) as substrates, respectively). Neither was the enzyme covalently inactivated to a significant degree. Spectroscopic and electrochemical analysis of the oxidation of a mixture of Dopa and the inhibitor demonstrated that the phosphonic compound reduced dopaquinone back to Dopa, thus diminishing and delaying the formation of dopachrome. This produces an apparent strong inhibitory effect when the reaction is monitored spectrophotometrically at 475 nm. In this peculiar case Dopa acts as a redox shuttle mediating the oxidation of the shorter phosphonic homolog. Decomposition of the phosphonic o-quinone to 3,4-dihydroxybenzaldehyde drives the reaction against the slightly unfavorable difference in redox potentials.
Beata Gasowska; Hubert Wojtasek; Józef Hurek; Marcin Drag; Kornel Nowak; Paweł Kafarski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of biochemistry / FEBS     Volume:  269     ISSN:  0014-2956     ISO Abbreviation:  Eur. J. Biochem.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-15     Completed Date:  2002-10-10     Revised Date:  2007-07-23    
Medline Journal Info:
Nlm Unique ID:  0107600     Medline TA:  Eur J Biochem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  4098-104     Citation Subset:  IM    
Institute of Chemistry, University of Opole, Poland.
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MeSH Terms
Agaricales / enzymology
Benzoquinones / metabolism*
Dihydroxyphenylalanine / analogs & derivatives*,  metabolism*
Enzyme Inhibitors / metabolism,  pharmacology*
Models, Chemical
Monophenol Monooxygenase / antagonists & inhibitors*
Oxygen / metabolism
Phosphonic Acids / metabolism,  pharmacology*
Plant Proteins / antagonists & inhibitors*
Reg. No./Substance:
0/Benzoquinones; 0/Enzyme Inhibitors; 0/Phosphonic Acids; 0/Plant Proteins; 0/amino-(3,4-dihydroxyphenyl)methylphosphonic acid; 4430-97-1/dopaquinone; 63-84-3/Dihydroxyphenylalanine; 7782-44-7/Oxygen; EC Monooxygenase
Erratum In:
Eur J Biochem 2002 Oct;269(20):5101

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