Investigation of the putative rate-limiting role of electron transfer in fatty acid desaturation using transfected HEK293T cells.

Elevated fatty acid (FA) levels contribute to severe metabolic diseases. Unbalanced oversupply of saturated FAs is particularly damaging, which renders stearoyl-CoA desaturase (SCD1) activity an important factor of resistance. A SCD1-related oxidoreductase protects cells against palmitate toxicity, so we aimed to test whether desaturase activity is limited by SCD1 itself or by the associated electron supply. Unsaturated/saturated FA ratio was markedly elevated by SCD1 overexpression while it remained unaffected by the overexpression of SCD1-related electron transfer proteins in HEK293T cells. Electron supply was not rate-limiting either in palmitate-treated cells or in cells with enhanced SCD1 expression. Our findings indicate the rate-limiting role of SCD1 itself, and that FA desaturation cannot be facilitated by reinforcing the electron supply of the enzyme.