Authors

M Cerone¹; TS Terry K Smith¹;  ¹ University of St Andrews, UK

Discussion

Trypanosomatids have an exclusive and finely regulated biosynthetic pathway for de novo synthesis of fatty acids (FAs) and particularly of polyunsaturated fatty acids (PUFAs). The key enzymes for the process of unsaturation are known as desaturases. In this work, we explored the activity of the putative Δ6-desaturase in T. brucei. Via GC-MS analysis of the fatty acids of the cells after genetic manipulation of the level of expression of Δ6-desaturases in both procyclic (PCF) and bloodstream (BSF) forms of T. brucei, and via supplementation of the media with FA sources, we showed that docosahexaenoic acid (22:6) and/or docosapentaenoic acid (22:5), and arachidonic acid (20:4) and/or docosatetraenoic acid (22:4) are the products and the substrates respectively of this Δ6-desaturases. Surprisingly, we were able to observe, via lipidomic analysis with ESI-MS/MS, an increase in inositol-phosphoryl ceramide (IPC) in response to the overexpression of Δ6-desaturases in low-fat media in BSF. The formation of IPC is normally only observed in the stumpy and procyclic forms of T. brucei. Therefore, the expression levels of Δ6-desaturases, which varies between BSF and PCF, might be involved in the cascade(s) of metabolic events that cause lipid remodelling and ultimately morphological changes, which are key to the transition between these life-cycle stages.