Fig. 9.

Schematic depicting the effect of SACLAC on sphingolipid pathway interactions for the promotion of cell death. The schematic is based on the MS results shown in Fig. 7 (HL-60/dnr cells exposed to SACLAC) and SACLAC cytotoxicity (shown in Fig. 4A). SACLAC inhibition of AC produces decreases in the AC product, sphingosine, and decreases in downstream S1P (down arrows). Due to AC inhibition, ceramide levels increase (up arrow). Excess ceramides elicit product inhibition of Des1 (dh-ceramide desaturase) (block sign), which in turn promotes a buildup of dh-ceramides (up arrow) resulting in product inhibition of dh-CerSs (block sign), promoting a sphinganine surplus (up arrow).