Abstract
Chem Biol Interact 2001 Oct 25;138(1):77-83 Related Articles, Books, LinkOut
Hypochlorous acid is a potent inhibitor of GST P1-1.
van Haaften RI, den Hartog GJ, Evelo CT, Haenen GR, Bast A.
Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, PO Box 616, 6200 MD, Maastricht, The Netherlands. r.vanhaaften@farmaco.unimaas.nl
Glutathione S-transferase is a phase II detoxification enzyme that can be inactivated by H(2)O(2). During oxidative stress various other reactive oxygen species are generated that are more reactive than the relatively stable H(2)O(2). Hypochlorous acid (HOCl) is a powerful oxidant which is highly reactive towards a range of biological substrates. We studied the influence of HOCl on the activity of GST P1-1. HOCl inhibits purified glutathione S-transferase P1-1 in a concentration dependent manner with an IC(50)-value of 0.6 microM, which is more than 1000 times as low as IC(50) reported for H(2)O(2). HOCl lowered the V(max) value, but did not affect the K(m) for CDNB. Our results show that HOCl is a potent, non-competitive inhibitor of GST P1-1. The relevance of this effect is discussed.
Hypochlorous acid is a potent inhibitor of GST P1-1.
van Haaften RI, den Hartog GJ, Evelo CT, Haenen GR, Bast A.
Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, PO Box 616, 6200 MD, Maastricht, The Netherlands. r.vanhaaften@farmaco.unimaas.nl
Glutathione S-transferase is a phase II detoxification enzyme that can be inactivated by H(2)O(2). During oxidative stress various other reactive oxygen species are generated that are more reactive than the relatively stable H(2)O(2). Hypochlorous acid (HOCl) is a powerful oxidant which is highly reactive towards a range of biological substrates. We studied the influence of HOCl on the activity of GST P1-1. HOCl inhibits purified glutathione S-transferase P1-1 in a concentration dependent manner with an IC(50)-value of 0.6 microM, which is more than 1000 times as low as IC(50) reported for H(2)O(2). HOCl lowered the V(max) value, but did not affect the K(m) for CDNB. Our results show that HOCl is a potent, non-competitive inhibitor of GST P1-1. The relevance of this effect is discussed.
| Original language | English |
|---|---|
| Pages (from-to) | 77-83 |
| Number of pages | 7 |
| Journal | Chemico-Biological Interactions |
| Volume | 138 |
| DOIs | |
| Publication status | Published - 1 Jan 2001 |