Roles of L-serine and sphingolipid synthesis in brain development and neuronal survival

Yoshio Hirabayashi, Shigeki Furuya

Research output: Contribution to journalReview article

49 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)188-203
Number of pages16
JournalProgress in Lipid Research
Volume47
Issue number3
DOIs
Publication statusPublished - May 1 2008

Fingerprint

Sphingolipids
Serine
Brain
Neurons
Phosphatidylserines
Biosynthesis
Membrane Lipids
Palmitoyl Coenzyme A
Amino Acids
Essential Amino Acids
Ceramides
Neurology
Neuroglia
Astrocytes
Transgenic Mice
Central Nervous System
Lipids
Glucose
Survival

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cite this

Roles of L-serine and sphingolipid synthesis in brain development and neuronal survival. / Hirabayashi, Yoshio; Furuya, Shigeki.

In: Progress in Lipid Research, Vol. 47, No. 3, 01.05.2008, p. 188-203.

Research output: Contribution to journalReview article

@article{5b8187b10d26421faf802c4164e09415,
title = "Roles of L-serine and sphingolipid synthesis in brain development and neuronal survival",
abstract = "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.",
author = "Yoshio Hirabayashi and Shigeki Furuya",
year = "2008",
month = "5",
day = "1",
doi = "10.1016/j.plipres.2008.01.003",
language = "English",
volume = "47",
pages = "188--203",
journal = "Progress in Lipid Research",
issn = "0163-7827",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - Roles of L-serine and sphingolipid synthesis in brain development and neuronal survival

AU - Hirabayashi, Yoshio

AU - Furuya, Shigeki

PY - 2008/5/1

Y1 - 2008/5/1

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.

UR - http://www.scopus.com/inward/record.url?scp=40849106310&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40849106310&partnerID=8YFLogxK

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 -