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Published on: January 14, 2013
Pharmacological Modulation of Glycosphingolipid Metabolism
Jin-Ichi Inokuchi1, Takashi Ode2,3, Miki Hara-Yokoyama4
1Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan. jin@tohoku-mpu.ac.jp.
Abstract:
The experimental approach to deplete cellular glycosphingolipids (GSLs) with the specific inhibitors of glycosphingolipid biosynthesis has the potential to identify functions of endogenous GSLs. Most GSLs are derived from glucosylceramide (GlcCer). D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) inhibits GIcCer synthase and has been used extensively to study the biological functions of living cells. D-PDMP inhibits mTORC1 activity, which is independent of its inhibitory activity on GlcCer synthase. We also developed an analog of D-PDMP, D-threo-1-phenyl-2-benzyloxycarbonylamino-3-pyrrolidino-1-propanol (D-PBPP) lacking the effect on mTORC1. Here, we summarize the effects of D-PDMP and D-PBPP on the metabolism of GSLs and cell growth.
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