New role for ceramide in hypoxia and insulin resistance

Figure 2 Ceramide synthesis pathways. Ceramides are synthesize through three ways, namely, de novo pathway, salvage pathway, and sphingomyelinase pathway. The de novo synthesis of ceramide commences with the condensation of serine and palmitate via action of serine palmitoyl-coenzyme A acyltransferase, followed by the continuous action of 3-keto-dihydrosphingosine reductase, dihydroceramide synthases, and dihydroceramide desaturase. In the sphingomyelinase pathway, ceramide can be produced from hydrolysis of sphingomyelin through the action of either acid or neutral sphingomyelinase, and ceramide also can synthesize sphingomyelin through the action of sphingomyelin synthase. The salvage pathway is more complex than the other two pathways. Glucosylceramide, complex sphingolipids, sphingosine, and sphingomyelin can generate ceramide from the action of diverse enzymes such as glucosylceramide synthase, LASS, and sphingomyelinase. SPT: Serine palmitoyl-coenzyme A acyltransferase; SMase: Sphingomyelinase; GCS: Glucosylceramide synthase.