Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves
The interaction of the product of H2O2 and (PhSe)2 with delta-aminolevulinate dehydratase (delta-ALA-D) from mammals and plants was investigated. (PhSe)2 inhibited rat hepatic delta-ALA-D with an IC50 of 10 µM but not the enzyme from cucumber leaves. The reaction of (PhSe)2 with H2O2 for 1 h increas...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Associação Brasileira de Divulgação Científica
2002-06-01
|
| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2002000600001 |
| _version_ | 1818309873548394496 |
|---|---|
| author | M. Farina N.B.V. Barbosa C.W. Nogueira V. Folmer G. Zeni L.H. Andrade A. L. Braga J.B.T. Rocha |
| author_facet | M. Farina N.B.V. Barbosa C.W. Nogueira V. Folmer G. Zeni L.H. Andrade A. L. Braga J.B.T. Rocha |
| author_sort | M. Farina |
| collection | DOAJ |
| description | The interaction of the product of H2O2 and (PhSe)2 with delta-aminolevulinate dehydratase (delta-ALA-D) from mammals and plants was investigated. (PhSe)2 inhibited rat hepatic delta-ALA-D with an IC50 of 10 µM but not the enzyme from cucumber leaves. The reaction of (PhSe)2 with H2O2 for 1 h increased the inhibitory potency of the original compound and the IC50 for animal delta-ALA-D inhibition was decreased from 10 to 2 µM. delta-ALA-D from cucumber leaves was also inhibited by the products of reaction of (PhSe)2 with H2O2 with an IC50 of 4 µM. The major product of reaction of (PhSe)2 with H2O2 was identified as seleninic acid and produced an intermediate with a lambdamax at 265 nm after reaction with t-BuSH. These results suggest that the interaction of (PhSe)2 with mammal delta-ALA-D requires the presence of cysteinyl residues in close proximity. Two cysteine residues in spatial proximity have been recently described for the mammalian enzyme. Analysis of the primary structure of plant delta-ALA-D did not reveal an analogous site. In contrast to (PhSe)2, seleninic acid, as a result of the higher electrophilic nature of its selenium atom, may react with additional cysteinyl residue(s) in mammalian delta-ALA-D and also with cysteinyl residues from cucumber leaves located at a site distinct from that found at the B and A sites in mammals. Although the interaction of organochalcogens with H2O2 may have some antioxidant properties, the formation of seleninic acid as a product of this reaction may increase the toxicity of organic chalcogens such as (PhSe)2. |
| first_indexed | 2024-12-13T07:37:05Z |
| format | Article |
| id | doaj.art-395b8f7075544c1eb151dd5d8c8d61cc |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-13T07:37:05Z |
| publishDate | 2002-06-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-395b8f7075544c1eb151dd5d8c8d61cc2022-12-21T23:55:03ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2002-06-0135662363110.1590/S0100-879X2002000600001Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leavesM. FarinaN.B.V. BarbosaC.W. NogueiraV. FolmerG. ZeniL.H. AndradeA. L. BragaJ.B.T. RochaThe interaction of the product of H2O2 and (PhSe)2 with delta-aminolevulinate dehydratase (delta-ALA-D) from mammals and plants was investigated. (PhSe)2 inhibited rat hepatic delta-ALA-D with an IC50 of 10 µM but not the enzyme from cucumber leaves. The reaction of (PhSe)2 with H2O2 for 1 h increased the inhibitory potency of the original compound and the IC50 for animal delta-ALA-D inhibition was decreased from 10 to 2 µM. delta-ALA-D from cucumber leaves was also inhibited by the products of reaction of (PhSe)2 with H2O2 with an IC50 of 4 µM. The major product of reaction of (PhSe)2 with H2O2 was identified as seleninic acid and produced an intermediate with a lambdamax at 265 nm after reaction with t-BuSH. These results suggest that the interaction of (PhSe)2 with mammal delta-ALA-D requires the presence of cysteinyl residues in close proximity. Two cysteine residues in spatial proximity have been recently described for the mammalian enzyme. Analysis of the primary structure of plant delta-ALA-D did not reveal an analogous site. In contrast to (PhSe)2, seleninic acid, as a result of the higher electrophilic nature of its selenium atom, may react with additional cysteinyl residue(s) in mammalian delta-ALA-D and also with cysteinyl residues from cucumber leaves located at a site distinct from that found at the B and A sites in mammals. Although the interaction of organochalcogens with H2O2 may have some antioxidant properties, the formation of seleninic acid as a product of this reaction may increase the toxicity of organic chalcogens such as (PhSe)2.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2002000600001delta-Aminolevulinate dehydrataseDiphenyl diselenideSeleninic acid |
| spellingShingle | M. Farina N.B.V. Barbosa C.W. Nogueira V. Folmer G. Zeni L.H. Andrade A. L. Braga J.B.T. Rocha Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves Brazilian Journal of Medical and Biological Research delta-Aminolevulinate dehydratase Diphenyl diselenide Seleninic acid |
| title | Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves |
| title_full | Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves |
| title_fullStr | Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves |
| title_full_unstemmed | Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves |
| title_short | Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves |
| title_sort | reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta aminolevulinate dehydratase from rat liver and cucumber leaves |
| topic | delta-Aminolevulinate dehydratase Diphenyl diselenide Seleninic acid |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2002000600001 |
| work_keys_str_mv | AT mfarina reactionofdiphenyldiselenidewithhydrogenperoxideandinhibitionofdeltaaminolevulinatedehydratasefromratliverandcucumberleaves AT nbvbarbosa reactionofdiphenyldiselenidewithhydrogenperoxideandinhibitionofdeltaaminolevulinatedehydratasefromratliverandcucumberleaves AT cwnogueira reactionofdiphenyldiselenidewithhydrogenperoxideandinhibitionofdeltaaminolevulinatedehydratasefromratliverandcucumberleaves AT vfolmer reactionofdiphenyldiselenidewithhydrogenperoxideandinhibitionofdeltaaminolevulinatedehydratasefromratliverandcucumberleaves AT gzeni reactionofdiphenyldiselenidewithhydrogenperoxideandinhibitionofdeltaaminolevulinatedehydratasefromratliverandcucumberleaves AT lhandrade reactionofdiphenyldiselenidewithhydrogenperoxideandinhibitionofdeltaaminolevulinatedehydratasefromratliverandcucumberleaves AT albraga reactionofdiphenyldiselenidewithhydrogenperoxideandinhibitionofdeltaaminolevulinatedehydratasefromratliverandcucumberleaves AT jbtrocha reactionofdiphenyldiselenidewithhydrogenperoxideandinhibitionofdeltaaminolevulinatedehydratasefromratliverandcucumberleaves |