Hoppe-Seyler's Z. Physiol. Chem. Bd. 354, S. 169-181, Februar 1973 Stereospecificities in the Metabolie Reactions of the four Isomeric Sphinganines (Dihydrosphingosines) in Rat Liver Wilhelm Stoffel* and Klaus Bister (Received 21 November 1972) Summary: The metabolism of the four optical isomers [(O( + )-eryfhro (=25,3/i); ^(-)-erythro (= 2/U5), O( + )-threo (= 2R y 3R) and L(-)-threo (=25,35)] of sphinganine (dihydrosphingosine) was studied in the rat. Convenient separation methods for the radioactive antipodes of the erythro and threo enantiomers are described. The stereo- chemical arrangement of the substituents around carbon atoms 2 and 3 determines the specificity of the reactions. Long chain fatty acids are transferred to the amino group of each isomeric long chain base with no preference for any antipode. The desaturation reaction to 4/-sphingenine (sphingosine) takes place at the sphinganine level as shown with [3- 14 C;3- 3 H]D( + )-^ry////O-sphinga- nine. The isotope ratio in 4/-sphingenine proved to be identical with that of the precursor sphinganine. Only O( + )-erythro (2S,3R) and L( — )-//jra?-sphin- ganine (25,35), which possess identical configura- tion at carbon atoms 2, are substrates in the desa- turation reaction. Only the two isomers (2S,3R) and (25,35)-sphinga- nine, are precursors for both with identical 25- configuration the synthesis of sphingomyelin and cerebrosides of rat liver. This result points to the high stereospecificity of the ceramide-CDP choline phosphorylcholine transferase and ceramide-UDP- galactose (glucose) galactose (glucose) transferase reactions. Sphingomyelin and cerebrosides con- tained predominantly D(+)-ery///r0-4/-sphingenine and L(—)-///ra?-4/-sphingenine, respectively, as bases. The sphinganine kinase transfers the phosphate group from ATP to O( + )-eryihro (2S,3R), D( + )- threo (2R,3R), L(-)-erythro (2R,3S) and L(-)- f//re0-sphinganine, (25,35). Although all four isomers form 1-phosphate esters, only D( + )-ery//iro-sphinganine is a substrate of the sphinganine-1-phosphate lyase. Stereospezifität der Stoffwechselreaktionen der vier isomeren Sphinganine in Rattenleber Zusammenfassung: Der Stoffwechsel der vier erythro (= 2R 9 3S), O(+)-(hreo (= 2R,3R) und optischen Isomeren des Sphinganins (Dihydro- L(-)-threo ( 25,35)] wurde in der Ratte unter- sphingosins) [D( + )-erythro (= 2S,3R) 9 L(—)- sucht. Es werden einfache Trennungsmethoden * Address: Prof. Dr. Dr. W. Stoffel, Institut für Physiologische Chemie der Universität Köln, D-5 Köln 41, Joseph- Stelzmann-Straße 52. Enzymes: Acyltransferase, acyl CoA: sphinganine TV-acyltransferase (EC 2.3.I.?; not yet listed) Ceramide cholinephosphotransferase, CDPcholinerceramide cholinephosphotransferase (EC 2.7.8.3) D-3-Dehydrosphinganinc reductase, D-sphinganine:NADP oxidoreductase (EC l.l.l.?; not yet listed) 3-Dehydrosphinganine synthetase, acyl-CoA:scrineC-2-acyltransfcrase(dccarboxylating) (EC2.3.I. ?; not yet listed) Sphinganine kinase, ATP:sphinganine 1-phosphotransferase (EC 2.7.1.?; not yet listed) Sphinganine-1-phosphate lyase, sphinganine-1-phosphate alkanal-lyase (EC 4.I.2.?; not yet listed). Abbreviations: TMS = trimethylsilyl; GLC = gas-liquid chromatography, stationary phases: SE 30 ethylene glycol succinate polyester; S = start; F = front. methyl silicone, EGS = Brought to you by | University of Arizona Authenticated Download Date | 5/26/15 11:01 AM