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Exp Parasitol ; 231: 108178, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34767777

RESUMEN

Dihydroxyacetone (DHA) can be used as an energy source by many cell types; however, it is toxic at high concentrations. The enzyme dihydroxyacetone kinase (DAK) has shown to be involved in DHA detoxification and osmoregulation. Among protozoa of the genus Trypanosoma, T. brucei, which causes sleeping sickness, is highly sensitive to DHA and does not have orthologous genes to DAK. Conversely, T. cruzi, the etiological agent of Chagas Disease, has two putative ATP-dependent DAK (TcDAKs) sequences in its genome. Here we show that T. cruzi epimastigote lysates present a DAK specific activity of 27.1 nmol/min/mg of protein and that this form of the parasite is able to grow in the presence of 2 mM DHA. TcDAK gene was cloned and the recombinant enzyme (recTcDAK) was expressed in Escherichia coli. An anti-recTcDAK serum reacted with a protein of the expected molecular mass of 61 kDa in epimastigotes. recTcDAK presented maximal activity using Mg+2, showing a Km of 6.5 µM for DHA and a K0.5 of 124.7 µM for ATP. As it was reported for other DAKs, recTcDAK activity was inhibited by FAD with an IC50 value of 0.33 mM. In conclusion, TcDAK is the first DAK described in trypanosomatids confirming another divergent metabolism between T. brucei and T. cruzi.


Asunto(s)
Fosfotransferasas (Aceptor de Grupo Alcohol)/aislamiento & purificación , Trypanosoma cruzi/enzimología , Secuencia de Aminoácidos , Animales , Western Blotting , Chlorocebus aethiops , Dihidroxiacetona/metabolismo , Dihidroxiacetona/toxicidad , Electroforesis en Gel de Poliacrilamida , Técnica del Anticuerpo Fluorescente , Masculino , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Osmorregulación , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Fosfotransferasas (Aceptor de Grupo Alcohol)/clasificación , Trypanosoma brucei brucei/efectos de los fármacos , Trypanosoma cruzi/efectos de los fármacos , Células Vero
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