Trypanosoma Cruzi trypanothione reductase is inactivated by peroxidase-generated phenothiazine cationic radicals

Authors: Gutierrez-Correa, Jose1; Fairlamb, Alan2; Stoppani, Andres1

Source: Free Radical Research, Volume 34, Number 4, 2001 , pp. 363-378(16)

Publisher: Informa Healthcare

Buy & download fulltext article:


Price: $43.96 plus tax (Refund Policy)


Trypanosoma cruzi trypanothione reductase (TR) was irreversibly inhibited by peroxidase/H 2 O 2/phenothiazine (PTZ) systems. TR inactivation depended on (a) time of incubation with the phenothiazine system; (b) the peroxidase nature and (c) the PTZ structure and concentration. With the most effective systems, TR inactivation kinetics were biphasic, with a relatively fast initial phase during which about 75% of the enzyme activity was lost, followed by a slower phase leading to total enzyme inactivation. GSH prevented TR inactivation by the peroxidase/H 2 O 2 /PTZ +· systems. Production of PTZ +· cation radicals by PTZ peroxidation was essential for TR inactivation. Horseradish peroxidase, leukocyte myeloperoxidase (MPO) and the pseudo-peroxidase myoglobin (Mb) were effective catalysts of PTZ +· production. Promazine, thioridazine, chlorpromazine, propionylpromazine prochlorperazine, perphenazine and trimeprazine were effective constituents of the HRP/H 2 O 2 /PTZ system. The presence of substituents at the PTZ nucleus position 2 exerted significant influence on PTZ activity, as shown by the different effects of 2-trifluoromethyl and 2-H or 2-chlorophenothiazines. The PTZ +· cation radicals disproportionation regenerated the non-radical PTZ molecule and produced the PTZ sulfoxide that was inactive on TR. Thiol compounds including GSH interacted with PTZ +· cation radicals transferring an electron from the sulfide anion to the PTZ +· , thus nullifying the PTZ +· biological and chemical activities.

Keywords: Trypanothione reductase; cationic radicals; horseradish peroxidase; myeloperoxidase; myoglobin; phenothiazine

Document Type: Research Article


Affiliations: 1: Bioenergetics Research Centre, School of Medicine, University of Buenos Aires, Paraguay 2155, 1121, Buenos Aires, Argentina 2: Division of Molecular Parasitology and Biological Chemistry, Department of Biochemistry, University of Dundee, Dundee, DD1, 5EH, United Kingdom

Publication date: January 1, 2001

More about this publication?
Related content


Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content

Text size:

A | A | A | A
Share this item with others: These icons link to social bookmarking sites where readers can share and discover new web pages. print icon Print this page