Practice question

Building sphingolipids requires creation of sphingoid long-chain base de novo in endoplasmic reticulum membrane through highly regulated steps essential for barrier formation. Serine palmitoyltransferase, heterodimer of SPTLC1 and SPTLC2 regulated by ORMDL feedback inhibition and small subunits ssSPTa/b that determine acyl chain preference, condenses L-serine and palmitoyl-CoA producing 3-ketodihydrosphingosine, reduced by 3-ketodihydrosphingosine reductase KDSR to dihydrosphingosine, also called sphinganine. Dihydrosphingosine is N-acylated by six ceramide synthases CerS isoforms with fatty-acyl specificity ranging C14 to C26 to dihydroceramide and desaturated by dihydroceramide desaturase DES1 to ceramide whose backbone is sphingosine, 2-amino-4-octadecene-1,3-diol. This amino alcohol thus represents defining precursor whose fatty acid chain can be remodeled via salvage pathway where sphingosine generated from sphingomyelin hydrolysis by acid sphingomyelinase is rapidly reacylated. Subsequent phosphorylation by sphingosine kinases 1 and 2 yields sphingosine-1-phosphate high-affinity ligand for S1PR1-5 GPCRs controlling lymphocyte egress from lymph nodes, angiogenesis, and vascular barrier integrity and immune regulation in mammals critically.