SPTLC1 and Insulin resistance: However, most important in the pathogenesis of insulin resistance is the de novo pathway, which begins in the endoplasmic reticulum by the action of the enzyme serine palmitoyltransferase 1 and 2 (SPTLC1 and SPTLC 2), producing 3-ketosphinganine from serine and palmitoyl-CoA.