Angelo Zinellu1, Salvatore Sotgia2, Bastianina Scanu2, Dionigia Arru2, Annalisa Cossu2, Anna Maria Posadino2, Roberta Giordo2, Arduino A Mangoni3, Gianfranco Pintus2, Ciriaco Carru4. 1. Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100, Sassari, Italy. azinellu@uniss.it. 2. Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100, Sassari, Italy. 3. Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia. 4. Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100, Sassari, Italy. carru@uniss.it.
Abstract
PURPOSE: The dietary flavonoids epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) have been shown to interact with circulating albumin for transport in blood to different body tissues. This interaction may modulate their bioavailability and effectiveness. METHODS: Using affinity capillary electrophoresis to assess binding constants (K b), we investigated whether posttranslational modification of human serum albumin (HSA) through N- and S-homocysteinylation, commonly observed in hyperhomocysteinemia, may modify its interaction with catechins. RESULTS: S-Hcy HSA had lower Kb values toward EC (14 %), EGC (18 %), ECG (24 %) and EGCG (30 %). Similarly, N-Hcy HSA had lower Kb values toward EC (17 %), EGC (22 %), ECG (23 %) and EGCG (32 %). No differences were observed in the affinity between catechins, albumin and mercaptalbumin. CONCLUSION: Therefore, HSA posttranslational modifications typical of hyperhomocysteinemia reduce its affinity to catechins, potentially affecting their pharmacokinetics and availability at the active sites.
PURPOSE: The dietary flavonoidsepicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) have been shown to interact with circulating albumin for transport in blood to different body tissues. This interaction may modulate their bioavailability and effectiveness. METHODS: Using affinity capillary electrophoresis to assess binding constants (K b), we investigated whether posttranslational modification of humanserum albumin (HSA) through N- and S-homocysteinylation, commonly observed in hyperhomocysteinemia, may modify its interaction with catechins. RESULTS: S-Hcy HSA had lower Kb values toward EC (14 %), EGC (18 %), ECG (24 %) and EGCG (30 %). Similarly, N-Hcy HSA had lower Kb values toward EC (17 %), EGC (22 %), ECG (23 %) and EGCG (32 %). No differences were observed in the affinity between catechins, albumin and mercaptalbumin. CONCLUSION: Therefore, HSA posttranslational modifications typical of hyperhomocysteinemia reduce its affinity to catechins, potentially affecting their pharmacokinetics and availability at the active sites.
Authors: H-H Sherry Chow; Iman A Hakim; Donna R Vining; James A Crowell; James Ranger-Moore; Wade M Chew; Catherine A Celaya; Steven R Rodney; Yukihiko Hara; David S Alberts Journal: Clin Cancer Res Date: 2005-06-15 Impact factor: 12.531