TY - JOUR
T1 - Roles of L-serine and sphingolipid synthesis in brain development and neuronal survival
AU - Hirabayashi, Yoshio
AU - Furuya, Shigeki
N1 - Funding Information:
The author’s work was supported by the RIKEN Brain Science Institute, the RIKEN President Discretionary Fund (to Y.H.); Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (JST) (to Y.H.); and Grants-in-Aid for Scientific Research Areas (C) No. 14580756 and (B) No. 18300125 (to S.F.) from the Japanese Ministry of Education, Culture, Sport, Science and Technology.
PY - 2008/5
Y1 - 2008/5
N2 - Sphingolipids represent a class of membrane lipids that contain a hydrophobic ceramide chain as its common backbone structure. Sphingolipid synthesis requires two simple components: l-serine and palmitoyl CoA. Although l-serine is classified as a non-essential amino acid, an external supply of l-serine is essential for the synthesis of sphingolipids and phosphatidylserine (PS) in particular types of central nervous system (CNS) neurons. l-Serine is also essential for these neurons to undergo neuritogenesis and to survive. Biochemical analysis has shown that l-serine is synthesized from glucose and released by astrocytes but not by neurons, which is the major reason why this amino acid is an essential amino acid for neurons. Biosynthesis of membrane lipids, such as sphingolipids, PS, and phosphatidylethanolamine (PE), in neurons is completely dependent on this astrocytic factor. Recent advances in lipid biology research using transgenic mice have demonstrated that synthesis of endogenous l-serine and neuronal sphingolipids is essential for brain development. In this review, we discuss the metabolic system that coordinates sphingolipid synthesis with the l-serine synthetic pathway between neurons and glia. We also discuss the crucial roles of the metabolic conversion of l-serine to sphingolipids in neuronal development and survival. Human diseases associated with serine and sphingolipid biosynthesis are also discussed.
AB - Sphingolipids represent a class of membrane lipids that contain a hydrophobic ceramide chain as its common backbone structure. Sphingolipid synthesis requires two simple components: l-serine and palmitoyl CoA. Although l-serine is classified as a non-essential amino acid, an external supply of l-serine is essential for the synthesis of sphingolipids and phosphatidylserine (PS) in particular types of central nervous system (CNS) neurons. l-Serine is also essential for these neurons to undergo neuritogenesis and to survive. Biochemical analysis has shown that l-serine is synthesized from glucose and released by astrocytes but not by neurons, which is the major reason why this amino acid is an essential amino acid for neurons. Biosynthesis of membrane lipids, such as sphingolipids, PS, and phosphatidylethanolamine (PE), in neurons is completely dependent on this astrocytic factor. Recent advances in lipid biology research using transgenic mice have demonstrated that synthesis of endogenous l-serine and neuronal sphingolipids is essential for brain development. In this review, we discuss the metabolic system that coordinates sphingolipid synthesis with the l-serine synthetic pathway between neurons and glia. We also discuss the crucial roles of the metabolic conversion of l-serine to sphingolipids in neuronal development and survival. Human diseases associated with serine and sphingolipid biosynthesis are also discussed.
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U2 - 10.1016/j.plipres.2008.01.003
DO - 10.1016/j.plipres.2008.01.003
M3 - Review article
C2 - 18319065
AN - SCOPUS:40849106310
VL - 47
SP - 188
EP - 203
JO - Progress in Lipid Research
JF - Progress in Lipid Research
SN - 0163-7827
IS - 3
ER -