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Biochemistry and cell biology of long chain sphingosine bases and sphingolipids, galactocerebrosides and sphingomyelin

Genetics, cell biology and biochemistry of sphingolipid synthesizing and degrading enzymes: Cerebroside synthase (UDP-galactosyl-ceramide transferase, CGT), acid (SMPD-1) and neutral sphingomyelinases (SMPD-2 and SMPD-3).
Sphingosine bases, dihydrosphingosine and sphingosine (long chain bases) form the backbone molecule of complex sphingolipids, important building blocks of biological membranes, particularly of myelin of central and peripheral nervous system.

We unravelled the complete biosynthetic (A) and catabolic (B) pathways of long chain sphingosine bases.

A. The key enzyme in the biosynthesis of long chain sphingosine bases is palmitoyl-CoA serine transferase (SPT). Palmitoyl-CoA and serine are condensed to 3-keto-2S-sphinganine, which is reduced by 3-ketosphinganine reductase, a NADPH dependent enzyme, to sphinganine. After acylation to ceramide the trans double bond is introduced in the acyl-4trans-sphinganine desaturase reaction.

B. The degradation of the long chain bases is initiated by the ATP dependent sphingosine-kinase (SP-1-K) reaction to sphingosine-1-phosphate, which has been recognized as a potential lipid second messenger molecule. SP1-P is cleaved in a pyridoxal phosphate dependent aldolase reaction by SP-1-phosphate aldolase to palmitaldehyde and ethanolamine phosphate. The reutilization of these degradation products in the phospholipid synthesis has been established in this laboratory.

Literature

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Human and Murine Serine-Palmitoyl-CoA Transferase (SPT): Cloning, Expression and Characterization of the Key Enzyme of Sphingolipid Synthesis
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W. Stoffel, I. Melzner (1980)
Studies in vitro on the biosynthesis of ceramide and sphingomyelin A reevaluation of proposed pathways Hoppe-Seyler's Zeitschr. Physiol. Chemie, 361, 755-771


W. Stoffel, K. Dittmar, R. Wilmes (1975)
Sphingolipid metabolism in bacteroide aceae
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W. Stoffel, K. Bister (1974)
Studies on the desaturation of sphinganine
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 355, 911-923


W. Stoffel, E. Bauer, J. Stahl (1974)
The metabolism of sphingosine bases in Tetrahymena pyriformis. Sphingosine kinase and sphingosine-1-phosphate lyase
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 355, 61-74


W. Stoffel, W. Därr (1974)
2-alkenal reductase. Isolation, properties and specificities
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 355, 54-60


W. Stoffel (1973)
Chemistry and biochemistry of sphingosine bases
Chemistry and Physics of Lipids, 11, 318-334


W. Stoffel, I. Melzner (1973)
Chemical synthesis of long chain 2-alkynals, alkynols, 2c- and 2t-alkenals and 2c- and 2t-alkenols Hoppe-Seyler's Zeitschr. Physiol. Chemie, 354, 1626-1632


W. Stoffel, B. Hellenbroich, G. Heimann (1973)
Properties and specificities of sphingosine kinase from blood platelets
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 354, 1311-1316
 

W. Stoffel (1973)
Sphingosine metabolism and its link to phospholipid biosynthesis
Enzymologia, Molecular & Cellular Biochemistry, 1, 147-155


R. Henning, W. Stoffel (1973)
Glycosphingolipids in lysosomal membranes
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 354, 760-770


W. Stoffel, G. Heimann, B. Hellenbroich (1973)
Sphingosine kinase in blood platelets
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 354, 562-566


W. Stoffel, K. Bister (1973)
Stereospecificities in the metabolic reactions of the four isomeric sphinganines (dihydrosphingosines) in rat liver
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 354, 169-181


W. Stoffel (1973)
Relationship between sphingolipid and phospholipid metabolism
Biochemical Society Transactions, 336-341


W. Stoffel, P. Hanfland (1973)
Analysis of amino sugar-containing glycosphingolipids by combined gas-liquid-chromatography and mass spectrometry
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G. Assmann, W. Stoffel (1972)
Metabolism of sphingosine bases XIX.
On the origin of phytosphingosine (4D-hydroxysphinganine) in mammalian tissues
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 353, 917-979


W. Stoffel, G. Assmann (1972)
Metabolism of sphingosine bases XVIII.
Degradation in vitro of phytosphingosine (4D-hydrosphinganine)
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 353, 965-970


H. Heckers, W. Stoffel (1972)
Sphingolipids in blood platelets of the pig
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 353, 407-418


W. Stoffel, G. Assmann (1972)
On the metabolism of sphinganyl- and sphingenylphosphorylcholine. Studies in vitro and in vivo
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 353, 65-74


G. Sticht, D. LeKim, W. Stoffel (1972)
Chemical synthesis of D,L-3-dehydrosphinganine, its C14-, C16- and C20-homologues and the resolution into the enantiomeric forms
Chem. Phys. Lipids, 8, 10-25


W. Stoffel, G. Assmann, K. Bister (1971)
Metabolism of sphingosine bases XVII.
Stereospecificities in the introduction of the 4t-double bond into sphinganine yielding 4t-sphingenine (sphingosine)
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 352, 1531-1544


W. Stoffel, D. LeKim, T. S. Tschung (1971)
A simple chemical method for labelling phosphatidylcholine and sphingomyelin in the choline moiety Hoppe-Seyler's Zeitschr. Physiol. Chemie, 352, 1058-1064


W. Stoffel, E. Binczek (1971)
Metabolism of sphingosine bases XVI.
Studies on the stereospecifity of the introduction of the hydroxy group of 4D-hydroxysphinganine (phytosphingosine)
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 352, 1065-1072


W. Stoffel, D. LeKim (1971)
Stereospecificity of the biochemical dehydrogenation of the 1-O-alkyl-glyceryl to the 1-O-alk-1'-enyl glyceryl ether bond
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 352, 501-511

 
W. Stoffel (1970)
Studies on the biosynthesis and degradation of sphingosine bases
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W. Stoffel, G. Assmann (1970)
Metabolism of sphingosine bases XV.
Enzymatic degradation of 4t-sphingenine 1-phosphate (sphingosine 1-phosphate) to 2t-hexadecen-1-al and ethanolamine phosphate
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 351, 1041-1049


W. Stoffel, D. LeKim, G. Heyn (1970)
Metabolism of sphingosine bases XIV.
Sphinganine (dihydrosphingosine), an effective donor of the alk-1'-enyl chain of plasmalogens
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 351, 875-883


W. Stoffel, G. Assmann, E. Binczek (1970)
Metabolism of sphingosine bases XIII.
Enzymatic synthesis of 1-phosphate esters of 4t-sphingenine (sphingosine), sphinganine (dihydrosphingosine), 4-hydroxysphinganine (phytosphingosine) and 3-dehydrosphinganine by erythrocytes
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 351, 635-642


W. Stoffel, A. Scheid (1969)
Metabolism of sphingosine bases XII.
Eicosasphinganine (eicosadihydrosphingosine) and 3-dehydroeicosasphinganine (3-dehydroeicosadihydrosphingosine)
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 350, 1593-1604


W. Stoffel, D. LeKim, G. Sticht (1969)
Metabolism of sphingosine bases XI.
Distribution and properties of dihydrosphingosine-1-phosphate aldolase (sphinganine-1-phosphate alkanal-lyase)
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 350, 1233-1241


R. Henning, W. Stoffel (1969)
The relationship between phospholipid biosynthesis, sphingosine degradation and serine metabolismHoppe-Seyler's Zeitschr. Physiol. Chemie, 350, 827-835


W. Stoffel, G. Sticht, D. LeKim (1969)
Metabolism of sphingosine bases X.
Degradation of [1-14C]-dihydrosphingosine (sphinganine) [1-14C]-2-amino-1,3-dihydroxyheptane and [1-14C]-dihydrosphingosine phosphate in rat liver
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 350, 63-68

W. Stoffel, G. Sticht, D. LeKim (1968)
Metabolism of sphingosine bases IX.
Degradation in vitro of dihydrosphingosine and dihydrosphingosine phosphate to palmitaldehyde and ethanolamine phosphate
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 349, 1745-1748


W. Stoffel, D. LeKim, G. Sticht (1968)
Metabolism of sphingosine bases VIII.
Stereospecifity of the NADPH-dependent reduction reaction of 3-oxodihydrosphingosine (2-amino-1-hydroxyoctadecane-3-one)
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 349, 1637-1644


W. Stoffel, R. Henning (1968)
Metabolism of sphingosine bases VII.
Studies on the metabolism of [1-3H]-erythro-D, L-sphingosine ([1-3H]-4t-sphingenine) during the myelination period of the rat
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 349, 1400-1404


W. Stoffel, G. Sticht, D. LeKim (1968)
Metabolism of sphingosine bases VI.
Synthesis and degradation of sphingosine bases in Hansenual ciferrii
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 349, 1149-1156


W. Stoffel, D. LeKim, G. Sticht (1968)
Metabolism of sphingosine bases V.
Biosynthesis of dihydrosphingosine in vitro
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 349, 664-670


W. Stoffel, D. LeKim, G. Sticht (1967)
Metabolism of sphingosine bases IV.
2-amino-1-hydroxyoctadecane-3-one (3-oxodihydrosphingosine), the common intermediate in the biosynthesis of dihydrosphingosine and sphingosine and in the degradation of dihydrosphingosine
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W. Stoffel, G. Sticht (1967)
Metabolism of sphingosine bases III.
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W. Stoffel, G. Sticht (1967)
Metabolism of sphingosine bases II.
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W. Stoffel, G. Sticht (1967)
Metabolism of sphingosine bases I.
Degradation and incorporation of [3-14C]-erythro-DL-Dihydrosphingosine and [7-3H2]-erythro-DL-sphingosine into sphingolipids of rat liver
Hoppe-Seyler's Zeitschr. Physiol. Chemie, 348, 941-943