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De Novo Sphingolipid Biosynthesis: A Necessary, but Dangerous, Pathway

Year: 2002
Type: review
Abstract: serine palmitoyltransferase Sphingolipids form specialized structures, mediate cell-cell and cell-substratum interactions, modulate the behavior of cellular proteins and receptors, and participate in signal transduction. They are synthesized de novo via a common backbone (sphinganine) that is modified to produce ceramides and more complex phospho- and glycosphingolipids. This minireview summarizes sphingoid base metabolism, function, and perturbation, including the participation of de novo sphingolipid biosynthesis in disease; other minireviews in this series will focus on ceramides (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar), sphingosine 1-phosphate (2Spiegel S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar), complex sphingolipids (3Kolter T. Proia R.L. Sandhoff K. J. Biol. Chem. 2002; 277: 25859-25862Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar), and sphingolipid trafficking (4van Meer G. Lisman Q. J. Biol. Chem. 2002; 277: 25855-25858Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar).Structural Diversity of Sphingoid BasesSphingoid bases 1Names in use for common sphingoid bases with those recommended by the IUPAC (7IUPAC-IUB Joint Commission on Biochemical Nomenclature Eur. J. Biochem. 1998; 257: 293-298Crossref PubMed Scopus (178) Google Scholar) shown in brackets are: sphingosine [(2S,3R,4E)- 2-aminooctadec-4-ene-1,3-diol and (E)-sphing-4-enine]; dihydrosphingosine [(2S,3R)-2-aminooctadecane-1,3-diol and sphinganine]; phytosphingosine and 4-hydroxysphinganine [(2S,3S,4R)-2-aminooctadecane-1,3,4-triol]. When alkyl chain length is not specified, it is assumed to be 18-carbon atoms; other lengths can be designated by a name or number prefix (such as icosasphingosine or C20-sphingosine for a sphingosine with 20 carbon atoms). are compounds with structural similarity to sphingosine from the root name (“sphingosin”) assigned to this family of alkaloidal lipids by Thudichum (5Thudichum J.L.W. A Treatise on the Chemical Constitution of Brain. Bailliere, Tindall, and Cox, London1884Google Scholar). They encompass a wide array of 2-amino-1,3-dihydroxyalkanes or -enes with (2S,3R)-erythro stereochemistry, alkyl chain lengths from 14 to 22 carbon atoms, 0 to 2 double bonds, and other modifications, such as hydroxyl group(s) at positions 4 or 6 and branching methyl groups at ω-l (iso), ω-2 (anti-iso), or elsewhere (6Karlsson K.-A. Lipids. 1970; 5: 6-43Crossref Scopus (243) Google Scholar, 7IUPAC-IUB Joint Commission on Biochemical Nomenclature Eur. J. Biochem. 1998; 257: 293-298Crossref PubMed Scopus (178) Google Scholar). Mammals produce mainly the species shown in Fig.1 plus small amounts of other chain length homologs; yeast have 18- and 20-carbon phytosphingosines and sphinganines (sphingoid bases with double bonds and hydroxyl and/or methyl groups are common in other fungi); and plants have unsaturated bases such as sphing-8-enines, sphing-4,8-dienes, and phytosphing-(8 or 9)-enines.Some organisms (such as fungi and sponges) produce compounds that are sphingoid base-like, examples of which are shown in Fig.2. As will be discussed later, at least some of these disrupt sphingolipid metabolism.Figure 2Examples of naturally occurring inhibitors for two key enzymes of sphingolipid biosynthesis as well as other sphingoid base-like compounds. More information on these inhibitors is given in the text. Calyxoside (65Zhou B.N. Mattern M.P. Johnson R.K. Kingston D.G.I. Tetrahedron. 2001; 57: 9459-9554Google Scholar) and BRS1 (66Willis R.H. De Vries Scopus Google Scholar) as compounds from for de novo sphingolipid biosynthesis is and the of sphingoid base of this by of serine palmitoyltransferase K. S. T. J. Biol. Chem. Full Text PDF PubMed Google Scholar, R.L. S. PubMed Scopus Google Scholar) or by or K. T. S. Biochem. PubMed Scopus Google Scholar) and De novo sphingolipid biosynthesis is for in sphingolipids are in the sphingoid bases are in the J. PubMed Scopus Google is that this compounds that behavior or via sphingolipid and that the can be and and or or of (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar, S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar). of the enzymes of sphingolipid be with serine which the of the which sphingoid bases as well as sphingosine is from sphingolipid or and which to and two and or and are for this R.L. PubMed Scopus Google Scholar) and to be K. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). A in not to be a K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of to other with to be the of the base with this R.L. PubMed Scopus Google Scholar). be for this K. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google in the common of 2001; PubMed Scopus Google Scholar, G. de 2001; PubMed Scopus Google Scholar). is to a J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google of is to be of the more that is the of and and is for with carbon atoms, other can be in by for the PubMed Scopus Google Scholar). palmitoyltransferase is by a number of and naturally occurring As for it with and other compounds PubMed Scopus Google Scholar, G. 2001; PubMed Scopus Google Scholar). More and inhibitors have from and S. T. T. Biochem. Scopus Google Scholar, PubMed Scopus Google Scholar). inhibitors which is have in the novo biosynthesis in T. 1998; PubMed Scopus Google be in the inhibitors K. T. S. Biochem. PubMed Scopus Google Scholar). which have in this is K. T. PubMed Scopus Google base can be by or sphingoid bases to in in J. PubMed Scopus Google Scholar) by of by sphingoid base G. T. T. Sandhoff K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). at a with a number of including and T. J. Biol. 1998; PubMed Scopus Google Scholar), J. 1998; Full Text Full Text PDF PubMed Google Scholar), T. S. G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and other L.M. Biochem. 2001; PubMed Scopus Google Scholar). of and in 2001; PubMed Scopus Google Scholar). of in to J. Y.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and in yeast Y.A. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). in yeast mainly sphingoid R.L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and in R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) and of G. Y.A. J. Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google of and of to in to of of the a of to and a family of of yeast for S. Biol. 2001; PubMed Scopus Google Scholar) to of the in other can be synthesized by the of S. Y.A. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and in yeast this of on to Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google is the of a number of inhibitors J. PubMed Scopus Google Scholar) such as that the backbone with the sphingoid base of and the with of the compounds with the backbone in are and inhibitors J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google of is of a as shown in J. G. G. Sandhoff K. Biochem. PubMed Scopus Google Scholar). This is ceramides are in (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar). This can be in or J. G. G. Sandhoff K. Biochem. PubMed Scopus Google G. J. Sandhoff K. J. Biol. Chem. Full Text Full Text PDF Scopus Google Scholar). have from plants Biochem. 2001; 293-298Crossref PubMed Scopus Google Scholar), to the of the and and a from S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). for that the G. J. Chem. 2001; PubMed Scopus Google Scholar), which is with the that of the and S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). A of the G. G. Chem. 2001; PubMed Scopus Google Scholar). for phytosphingosine have in yeast K. T. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), plants S. 2001; PubMed Scopus Google Scholar), and S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). that can with the sphingoid base and at least in yeast R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) in enzymes that and for complex the sphingoid base well as the that this and the that sphingoid base to a and will be discussed in the minireviews (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar, S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar, T. Proia R.L. Sandhoff K. J. Biol. Chem. 2002; 277: 25859-25862Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar, Meer G. Lisman Q. J. Biol. Chem. 2002; 277: 25855-25858Abstract Full Text Full Text PDF PubMed Scopus (184) Google of de in of de novo sphingolipid biosynthesis can be as shown for the 2001; PubMed Scopus Google Scholar). are of that a of and and and other 2001; PubMed Scopus Google Scholar). the of in and which is as a of 2001; PubMed Scopus Google Scholar). of to be for of the of these of complex sphingolipids the of some such as the J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and to T. and in that the of de novo sphingolipid biosynthesis and some that amounts and are some of the from the of which is to or 1-phosphate is not more complex sphingolipids which are of of inhibitors and are of these are for a are to be other some of these is to in the in have these in can 1-phosphate and Scholar) and of J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and sphingoid base are and (2Spiegel S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar), this for at least the of by in some J. J. Biol. Chem. Full Text PDF PubMed Google Scholar) and the of from of de novo synthesized of the of this can be to and other T. S. G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). in some are This it is that de novo sphingolipid biosynthesis in by a wide of by and K. Full Text PDF PubMed Scopus Google Scholar) in of of be in some of the of and 1998; Google Scholar, PubMed Scopus Google Scholar), and J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, 2001; Full Text Full Text PDF PubMed Scopus Google Scholar), and in of or by or other T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) This for a wide of and as of the for R.H. 2002; PubMed Scopus Google compounds with such a of and these compounds have that de novo sphingolipid biosynthesis and are for from in these and in organisms for as in the with which the to of the of compounds via complex sphingolipid and de novo biosynthesis are as amounts of the (sphingoid bases and can be to by sphingolipid and serine are the sphingolipid can be with of the cellular of complex the compounds be more to the are the and of these species be with other such as or not the are and and the (such as the of can be modified to more be that de novo sphingolipid biosynthesis and and of of these species as well as and are and Y.A. 2001; PubMed Scopus Google Scholar). This is as by Thudichum (5Thudichum J.L.W. A Treatise on the Chemical Constitution of Brain. Bailliere, Tindall, and Cox, London1884Google Scholar) in that lipids are and of that of plants as well as Sphingolipids form specialized structures, mediate cell-cell and cell-substratum interactions, modulate the behavior of cellular proteins and receptors, and participate in signal transduction. They are synthesized de novo via a common backbone (sphinganine) that is modified to produce ceramides and more complex phospho- and glycosphingolipids. This minireview summarizes sphingoid base metabolism, function, and perturbation, including the participation of de novo sphingolipid biosynthesis in disease; other minireviews in this series will focus on ceramides (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar), sphingosine 1-phosphate (2Spiegel S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar), complex sphingolipids (3Kolter T. Proia R.L. Sandhoff K. J. Biol. Chem. 2002; 277: 25859-25862Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar), and sphingolipid trafficking (4van Meer G. Lisman Q. J. Biol. Chem. 2002; 277: 25855-25858Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar). Diversity of Sphingoid BasesSphingoid bases 1Names in use for common sphingoid bases with those recommended by the IUPAC (7IUPAC-IUB Joint Commission on Biochemical Nomenclature Eur. J. Biochem. 1998; 257: 293-298Crossref PubMed Scopus (178) Google Scholar) shown in brackets are: sphingosine [(2S,3R,4E)- 2-aminooctadec-4-ene-1,3-diol and (E)-sphing-4-enine]; dihydrosphingosine [(2S,3R)-2-aminooctadecane-1,3-diol and sphinganine]; phytosphingosine and 4-hydroxysphinganine [(2S,3S,4R)-2-aminooctadecane-1,3,4-triol]. When alkyl chain length is not specified, it is assumed to be 18-carbon atoms; other lengths can be designated by a name or number prefix (such as icosasphingosine or C20-sphingosine for a sphingosine with 20 carbon atoms). are compounds with structural similarity to sphingosine from the root name (“sphingosin”) assigned to this family of alkaloidal lipids by Thudichum (5Thudichum J.L.W. A Treatise on the Chemical Constitution of Brain. Bailliere, Tindall, and Cox, London1884Google Scholar). They encompass a wide array of 2-amino-1,3-dihydroxyalkanes or -enes with (2S,3R)-erythro stereochemistry, alkyl chain lengths from 14 to 22 carbon atoms, 0 to 2 double bonds, and other modifications, such as hydroxyl group(s) at positions 4 or 6 and branching methyl groups at ω-l (iso), ω-2 (anti-iso), or elsewhere (6Karlsson K.-A. Lipids. 1970; 5: 6-43Crossref Scopus (243) Google Scholar, 7IUPAC-IUB Joint Commission on Biochemical Nomenclature Eur. J. Biochem. 1998; 257: 293-298Crossref PubMed Scopus (178) Google Scholar). Mammals produce mainly the species shown in Fig.1 plus small amounts of other chain length homologs; yeast have 18- and 20-carbon phytosphingosines and sphinganines (sphingoid bases with double bonds and hydroxyl and/or methyl groups are common in other fungi); and plants have unsaturated bases such as sphing-8-enines, sphing-4,8-dienes, and phytosphing-(8 or 9)-enines.Some organisms (such as fungi and sponges) produce compounds that are sphingoid base-like, examples of which are shown in Fig.2. As will be discussed later, at least some of these disrupt sphingolipid Sphingoid bases 1Names in use for common sphingoid bases with those recommended by the IUPAC (7IUPAC-IUB Joint Commission on Biochemical Nomenclature Eur. J. Biochem. 1998; 257: 293-298Crossref PubMed Scopus (178) Google Scholar) shown in brackets are: sphingosine [(2S,3R,4E)- 2-aminooctadec-4-ene-1,3-diol and (E)-sphing-4-enine]; dihydrosphingosine [(2S,3R)-2-aminooctadecane-1,3-diol and sphinganine]; phytosphingosine and 4-hydroxysphinganine [(2S,3S,4R)-2-aminooctadecane-1,3,4-triol]. When alkyl chain length is not specified, it is assumed to be 18-carbon atoms; other lengths can be designated by a name or number prefix (such as icosasphingosine or C20-sphingosine for a sphingosine with 20 carbon atoms). are compounds with structural similarity to sphingosine from the root name (“sphingosin”) assigned to this family of alkaloidal lipids by Thudichum (5Thudichum J.L.W. A Treatise on the Chemical Constitution of Brain. Bailliere, Tindall, and Cox, London1884Google Scholar). They encompass a wide array of 2-amino-1,3-dihydroxyalkanes or -enes with (2S,3R)-erythro stereochemistry, alkyl chain lengths from 14 to 22 carbon atoms, 0 to 2 double bonds, and other modifications, such as hydroxyl group(s) at positions 4 or 6 and branching methyl groups at ω-l (iso), ω-2 (anti-iso), or elsewhere (6Karlsson K.-A. Lipids. 1970; 5: 6-43Crossref Scopus (243) Google Scholar, 7IUPAC-IUB Joint Commission on Biochemical Nomenclature Eur. J. Biochem. 1998; 257: 293-298Crossref PubMed Scopus (178) Google Scholar). Mammals produce mainly the species shown in Fig.1 plus small amounts of other chain length homologs; yeast have 18- and 20-carbon phytosphingosines and sphinganines (sphingoid bases with double bonds and hydroxyl and/or methyl groups are common in other fungi); and plants have unsaturated bases such as sphing-8-enines, sphing-4,8-dienes, and phytosphing-(8 or organisms (such as fungi and sponges) produce compounds that are sphingoid base-like, examples of which are shown in Fig.2. As will be discussed later, at least some of these disrupt sphingolipid De for de novo sphingolipid biosynthesis is and the of sphingoid base of this by of serine palmitoyltransferase K. S. T. J. Biol. Chem. Full Text PDF PubMed Google Scholar, R.L. S. PubMed Scopus Google Scholar) or by or K. T. S. Biochem. PubMed Scopus Google Scholar) and De novo sphingolipid biosynthesis is for in sphingolipids are in the sphingoid bases are in the J. PubMed Scopus Google is that this compounds that behavior or via sphingolipid and that the can be and and or or of (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar, S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar). of the enzymes of sphingolipid be with serine which the of the which sphingoid bases as well as sphingosine is from sphingolipid or and which to and two and or and are for this R.L. PubMed Scopus Google Scholar) and to be K. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). A in not to be a K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of to other with to be the of the base with this R.L. PubMed Scopus Google Scholar). be for this K. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google in the common of 2001; PubMed Scopus Google Scholar, G. de 2001; PubMed Scopus Google Scholar). is to a J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google of is to be of the more that is the of and and is for with carbon atoms, other can be in by for the PubMed Scopus Google Scholar). palmitoyltransferase is by a number of and naturally occurring As for it with and other compounds PubMed Scopus Google Scholar, G. 2001; PubMed Scopus Google Scholar). More and inhibitors have from and S. T. T. Biochem. Scopus Google Scholar, PubMed Scopus Google Scholar). inhibitors which is have in the novo biosynthesis in T. 1998; PubMed Scopus Google be in the inhibitors K. T. S. Biochem. PubMed Scopus Google Scholar). which have in this is K. T. PubMed Scopus Google base can be by or sphingoid bases to in in J. PubMed Scopus Google Scholar) by of by sphingoid base G. T. T. Sandhoff K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). at a with a number of including and T. J. Biol. 1998; PubMed Scopus Google Scholar), J. 1998; Full Text Full Text PDF PubMed Google Scholar), T. S. G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and other L.M. Biochem. 2001; PubMed Scopus Google Scholar). of and in 2001; PubMed Scopus Google Scholar). of in to J. Y.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and in yeast Y.A. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). in yeast mainly sphingoid R.L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and in R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) and of G. Y.A. J. Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google of and of to in to of of the a of to and a family of of yeast for S. Biol. 2001; PubMed Scopus Google Scholar) to of the in other can be synthesized by the of S. Y.A. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and in yeast this of on to Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google is the of a number of inhibitors J. PubMed Scopus Google Scholar) such as that the backbone with the sphingoid base of and the with of the compounds with the backbone in are and inhibitors J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google of is of a as shown in J. G. G. Sandhoff K. Biochem. PubMed Scopus Google Scholar). This is ceramides are in (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar). This can be in or J. G. G. Sandhoff K. Biochem. PubMed Scopus Google G. J. Sandhoff K. J. Biol. Chem. Full Text Full Text PDF Scopus Google Scholar). have from plants Biochem. 2001; 293-298Crossref PubMed Scopus Google Scholar), to the of the and and a from S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). for that the G. J. Chem. 2001; PubMed Scopus Google Scholar), which is with the that of the and S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). A of the G. G. Chem. 2001; PubMed Scopus Google Scholar). for phytosphingosine have in yeast K. T. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), plants S. 2001; PubMed Scopus Google Scholar), and S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). that can with the sphingoid base and at least in yeast R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) in enzymes that and for complex the sphingoid base well as the that this and the that sphingoid base to a and will be discussed in the minireviews (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar, S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar, T. Proia R.L. Sandhoff K. J. Biol. Chem. 2002; 277: 25859-25862Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar, Meer G. Lisman Q. J. Biol. Chem. 2002; 277: 25855-25858Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar). for de novo sphingolipid biosynthesis is and the of sphingoid base of this by of serine palmitoyltransferase K. S. T. J. Biol. Chem. Full Text PDF PubMed Google Scholar, R.L. S. PubMed Scopus Google Scholar) or by or K. T. S. Biochem. PubMed Scopus Google Scholar) and De novo sphingolipid biosynthesis is for in sphingolipids are in the sphingoid bases are in the J. PubMed Scopus Google Scholar). is that this compounds that behavior or via sphingolipid and that the can be and and or or of (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar, S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar). of the enzymes of sphingolipid be with serine which the of the which sphingoid bases as well as sphingosine is from sphingolipid or and which to and two and or and are for this R.L. PubMed Scopus Google Scholar) and to be K. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). A in not to be a K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of to other with to be the of the base with this R.L. PubMed Scopus Google Scholar). be for this K. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google in the common of 2001; PubMed Scopus Google Scholar, G. de 2001; PubMed Scopus Google Scholar). is to a J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google of is to be of the more that is the of and and is for with carbon atoms, other can be in by for the PubMed Scopus Google Scholar). palmitoyltransferase is by a number of and naturally occurring As for it with and other compounds PubMed Scopus Google Scholar, G. 2001; PubMed Scopus Google Scholar). More and inhibitors have from and S. T. T. Biochem. Scopus Google Scholar, PubMed Scopus Google Scholar). inhibitors which is have in the novo biosynthesis in T. 1998; PubMed Scopus Google be in the inhibitors K. T. S. Biochem. PubMed Scopus Google Scholar). which have in this is K. T. PubMed Scopus Google base can be by or sphingoid bases to in in J. PubMed Scopus Google Scholar) by of by sphingoid base G. T. T. Sandhoff K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). at a with a number of including and T. J. Biol. 1998; PubMed Scopus Google Scholar), J. 1998; Full Text Full Text PDF PubMed Google Scholar), T. S. G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and other L.M. Biochem. 2001; PubMed Scopus Google Scholar). of and in 2001; PubMed Scopus Google Scholar). of in to J. Y.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and in yeast Y.A. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). in yeast mainly sphingoid R.L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and in R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) and of G. Y.A. J. Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google of and of to in to of of the a of to and a family of of yeast for S. Biol. 2001; PubMed Scopus Google Scholar) to of the in other can be synthesized by the of S. Y.A. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and in yeast this of on to Obeid L.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google is the of a number of inhibitors J. PubMed Scopus Google Scholar) such as that the backbone with the sphingoid base of and the with of the compounds with the backbone in are and inhibitors J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google of is of a as shown in J. G. G. Sandhoff K. Biochem. PubMed Scopus Google Scholar). This is ceramides are in (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar). This can be in or J. G. G. Sandhoff K. Biochem. PubMed Scopus Google G. J. Sandhoff K. J. Biol. Chem. Full Text Full Text PDF Scopus Google Scholar). have from plants Biochem. 2001; 293-298Crossref PubMed Scopus Google Scholar), to the of the and and a from S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). for that the G. J. Chem. 2001; PubMed Scopus Google Scholar), which is with the that of the and S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). A of the G. G. Chem. 2001; PubMed Scopus Google Scholar). for phytosphingosine have in yeast K. T. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), plants S. 2001; PubMed Scopus Google Scholar), and S. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). that can with the sphingoid base and at least in yeast R.L. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) in enzymes that and for complex the sphingoid base well as the that this and the that sphingoid base to a and will be discussed in the minireviews (1Hannun Y.A. Obeid L.M. J. Biol. Chem. 2002; 277: 25847-25850Abstract Full Text Full Text PDF PubMed Scopus (739) Google Scholar, S. Milstien S. J. Biol. Chem. 2002; 277: 25843-25846Abstract Full Text Full Text PDF PubMed Scopus (508) Google Scholar, T. Proia R.L. Sandhoff K. J. Biol. Chem. 2002; 277: 25859-25862Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar, Meer G. Lisman Q. J. Biol. Chem. 2002; 277: 25855-25858Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar). and two and or and are for this R.L. PubMed Scopus Google Scholar) and to be K. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). A in not to be a K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of to other with to be the of the base with this R.L. PubMed Scopus Google Scholar). be for this K. T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google in the common of 2001; PubMed Scopus Google Scholar, G. de 2001; PubMed Scopus Google Scholar).
DOI: 10.1074/jbc.r200009200
Language: English
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2076091755
FWCI: 2.637
Cites: 67
Cited by: 633
Related to: 10