Highly specific methyl-end fatty-acid desaturases of trypanosomatids

ANDRÉS ALLOATTI; ANTONIO D. UTTARO

MOLECULAR AND BIOCHEMICAL PARASITOLOGY

ELSEVIER SCIENCE BV

Año: 2010

0166-6851

ESTE MANUSCRITO HA SIDO ACEPTADO CON CORRECCIONES EN: MOL. BIOCHEM. PARASITOL (2010) Abstract A detailed analysis of the trypanosomatids´ genome projects revealed the presence of genes predicted to encode fatty-acid desaturases of methyl-end type (MED). After cloning and functional characterization of all identified genes, it can be concluded that T. brucei contains a unique MED with oleate desaturase (OD) activity, T. cruzi has two ODs and L. major contains one OD and two active linoleate desaturases (LD). All characterized ODs are highly specific for oleate (18:1D9) as substrate, presenting a n + 3 regioselectivity, although palmitoleate (16:1D9) can be desaturated as well to a lesser extent. L. major LD appears to use exclusively linoleate (18:2n-6), converting it into a-linolenate (18:3n-3). This strong specificity assures no further conversion of polyunsaturated fatty acids (PUFAs) of the n-6 series into the n-3 series, downstream in the PUFA biosynthesis pathway. This characterization completes the identification of all enzymes involved in PUFA biosynthesis in a parasitic protist. Differently from T. brucei OD, T. cruzi and L. major orthologues are more active when expressed in the presence of trienoic fatty acids. This could be evidence for a post-translational regulation of these enzymes by a direct sensing of environmental parameters such as membrane fluidity or composition.