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Synthesis and Biological Activity of Homohypotaurine Obtained by the Enzyme-Based Conversion of Homocysteine Sulfinic Acid Using Recombinant Escherichia Coli Glutamate Decarboxylase.
Fontana, Mario; Gunaydin Akyildiz, Aysenur; D'Alonzo, Chiara; Giovannercole, Fabio; Zicchi, Arianna; Francioso, Antonio; Capuozzo, Elisabetta; De Biase, Daniela.
Afiliación
  • Fontana M; Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
  • Gunaydin Akyildiz A; Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Istanbul, Turkey.
  • D'Alonzo C; Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
  • Giovannercole F; Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
  • Zicchi A; Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
  • Francioso A; Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
  • Capuozzo E; Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
  • De Biase D; Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
Molecules ; 29(17)2024 Aug 23.
Article en En | MEDLINE | ID: mdl-39274833
ABSTRACT
l-Homocysteine, formed from S-adenosyl methionine following demethylation and adenosine release, accumulates when the methionine recycling pathway and other pathways become impaired, thus leading to hyperhomocysteinemia, a biomarker in cardiovascular diseases, neurological/psychiatric disorders, and cancer. The partial oxidation of the l-homocysteine thiol group and its decarboxylation on C-alpha lead to the formation of l-homocysteinesulfinic acid (l-HCSA) and homohypotaurine (HHT), respectively. Both compounds are not readily available from commercial suppliers, which hinders the investigation of their biological activities. Herein, the chemical synthesis of l-HCSA, from l-homocystine, was the starting point for establishing the bio-based synthesis of HHT using recombinant Escherichia coli glutamate decarboxylase (EcGadB), an enzyme already successfully employed for the bio-based synthesis of GABA and its phosphinic analog. Prior to HHT synthesis, kcat (33.92 ± 1.07) and KM (38.24 ± 3.45 mM) kinetic constants were determined for l-HCSA on EcGadB. The results of our study show that the EcGadB-mediated synthesis of HHT can be achieved with good yields (i.e., 40% following enzymatic synthesis and column chromatography). Purified HHT was tested in vitro on primary human umbilical vein endothelial cells and rat cardiomyoblasts and compared to the fully oxidized analog, homotaurine (OT, also known as tramiprosate), in widespread pharmaceutical use. The results show that both cell lines display statistically significant recovery from the cytotoxic effects induced by H2O2 in the presence of HHT.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Escherichia coli / Glutamato Descarboxilasa / Homocisteína Límite: Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Escherichia coli / Glutamato Descarboxilasa / Homocisteína Límite: Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza