FIGURE 1.

(A) Sphingolipid biosynthesis and degradation pathways. Ceramide (Cer) is the central core of sphingolipid metabolism, which is generated through the de novo synthesis pathway starting from serine and palmintoyl CoA, the SMase pathway by direct degradation of sphingomyelin (SM), and phosphorylation degradation of ceraminde-1-phosphate (C1P). Under the action of ceramidase, Cer is converted into sphingosine (Sph), which can be further phosphorylated by SphKs to form S1P. S1P lyase catalyzes irreversible exit from this pathway. Cer and Sph induce cell cycle arrest and apoptosis, whereas C1P and S1P promote cell proliferation and growth and induce inflammation. (B) The balance of sphingolipid-rheostat. Interconversion between Cer/Sph and S1P via SphKs. Cer/Sph induced cell death, whereas S1P promoted cell proliferation and survival. Sphingolipid-rheostat is formed between Cer/Sph and S1P, which determines cell death or survival. SphKs has intrinsic catalytic activity that helps maintain normal physiological levels through the balance of sphingolipid-rheostat, and is also influenced by Erk1/2, growth factors, and transcription level.