Curcumin-glutathione interactions and the role of human glutathione S-transferase P1-1.
Chemico-biological interactions
confidence
Key findings
GSTP1-1 accelerates GSH-mediated curcumin consumption, forms mono/di-glutathionyl adducts, and catalyzes reverse reaction; substrate inhibition observed.
View source on PubMed (PMID 10996298) ↗
- Sample size
- N/A
- Population
- In vitro biochemical study (recombinant human GSTP1-1, no living subjects)
- Dosing
- Curcumin apparent Km 25±11 µM; 1 mM GSH; 10 mM potassium phosphate pH 7.0
- Duration
- N/A
- Route
- in vitro
- Blinding
- not_reported
- Controls
- none
- Drug class
- polyphenol
Full abstract
Curcumin (diferuloylmethane), a yellow pigment of turmeric with antioxidant properties has been shown to be a cancer preventative in animal studies. It contains two electrophilic alpha, beta-unsaturated carbonyl groups, which can react with nucleophilic compounds such as glutathione (GSH), but formation of the GSH-curcumin conjugates has not previously been demonstrated. In the present studies, we investigated the reactions of curcumin with GSH and the effect of recombinant human glutathione S-transferase(GST)P1-1 on reaction kinetics. Glutathionylated products of curcumin identified by FAB-MS and MALDI-MS included mono- and di-glutathionyl-adducts of curcumin as well as cyclic rearrangement products of GSH adducts of feruloylmethylketone (FMK) and feruloylaldehyde (FAL). The presence of GSTP1-1 significantly accelerated the initial rate of GSH-mediated consumption of curcumin in 10 mM potassium phosphate, pH 7.0, and 1 mM GSH. GSTP1-1 kinetics determined using HPLC indicated substrate inhibition (apparent K(m) for curcumin of 25+/-11 microM, and apparent K(i) for curcumin of 8+/-3 microM). GSTP1-1 was also shown to catalyze the reverse reaction leading to the formation of curcumin from GSH adducts of FMK and FAL.