PubMed · 5481015
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Y Marquis. 1970. [Ethacrynic acid].. https://pubmed.ncbi.nlm.nih.gov/5481015/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
The reversibility of the conjugation reaction of the diuretic drug ethacrynic acid (EA), an alpha,beta-unsaturated ketone, with glutathione and glutathione S-transferase P1-1 (GST P1-1) has been studied. When the glutathione conjugate of EA was incubated with a 5-fold molar excess of N-acetyl-L-cysteine or GST P1-1, a time-dependent transfer of EA to N-acetyl-L-cysteine or GST P1-1 was observed. With increasing pH, the pseudo first order rate constants of transfer of EA to N-acetyl-L-cysteine increased from 0.010 h-1 (pH 6.4) to 0.040 h-1 (pH 7.4) and 0.076 h-1 (pH 8.4). From the fact that preincubation of GST P1-1 with 1-chloro-2,4-dinitrobenzene reduced the incorporation of [14C]EA from 0.94 +/- 0.21 (SD) to 0.16 +/- 0.02 mol EA/mol subunit and from automated Edman degradation of the major radioactive peptide isolated after pepsin digestion of the [14C]EA-labeled enzyme, it was concluded that the reaction of EA takes place with cysteine 47 of GST P1-1. When GST P1-1 was inactivated with a 5-fold molar excess of EA, adding an excess of glutathione resulted in full restoration of the catalytic activity in about 120 h. These findings may have several implications. Under normal physiological conditions the inhibition of GST P1-1 by covalent binding of EA would be reversed by glutathione, leaving reversible inhibition by the glutathione conjugate of EA and by EA itself as the main mechanism of inhibition; however, when glutathione levels are low the covalent inhibition might be predominant, resulting in a completely different time course for the inhibition.
Explore the source record for details and available documents.
Explore the source record for details and available documents.