Functional characterization of enzymes involved in cysteine biosynthesis and H2S production in Trypanosoma cruzi

MARCIANO, DANIELA; SANTANA, MARIANELA; NOWICKI, CRISTINA

MOLECULAR AND BIOCHEMICAL PARASITOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012

0166-6851

Trypanosoma cruzi is expected to synthetize de novo cysteine by different routes, among which thetwo-step pathway involving serine acetyltransferase and cysteine synthase (CS) is comprised. Also, cystathionine synthase (CBS) might contribute to the de novo generation of cysteine in addition to catalyzethe first step of the reverse transsulfuration route producing cystathionine. However, neither the functionalityof CS nor that of cystathionine lyase (CGL) has been assessed. Our results show that T. cruziCS could participate notably more actively than CBS in the de novo synthesis of cysteine. Interestingly,at the protein level T. cruzi CS is more abundant in amastigotes than in epimastigotes. Unlike the mammalianhomologues, T. cruzi CGL specifically cleaves cystathionine into cysteine and is unable to produceH2S. The expression pattern of T. cruzi CGL parallels that of CBS, which unexpectedly suggests that inaddition to the de novo synthesis of cysteine, the reverse transsulfuration pathway could be operativein the mammalian and insect stages. Besides, T. cruzi CBS produces H2S by decomposing cysteine or viacondensation of cysteine with homocysteine. The latter reaction leads to cystathionine production, andis catalyzed remarkably more efficiently than the breakdown of cysteine. In T. cruzi like in other organisms,H2S could exert regulatory effects on varied metabolic processes. Notably, T. cruzi seems to counton stage-specific routes involved in cysteine production, the multiple cysteine-processing alternativescould presumably reflect this parasite?s high needs of reducing power for detoxification of reactive oxygenspecies.