title: Studies in vitro on the biosynthesis of ceramide and sphingomyelin. A reevaluation of proposed pathways.
abstract: The postulated biosynthetic-pathways of ceramide and sphingomyelin were reinvestigated in extensive investigations by means of synthetic stereo- and radio-chemically pure substrates of high specific radioactivity. As a result, the synthesis of ceramides requires the acyl-CoA-mediated acyltransfer to the long chain bases sphingenine and sphinganine. During the biosynthesis of sphingomyelins, phosphocholine is being transferred from the donor CDP-choline to the primary alcohol group of ceramides. Neither can the free long chain sphingosine bases act as acceptor molecule for the phosphocholine group from CDP-choline, nor has a transfer of [N-14CH3]phosphocholine from [N-14CH3]phosphatidyl choline to ceramide by rat liver enzyme preparations been observed. In agreement with previous studies in vivo, the acylation of sphingenylphosphocholine by acyl-CoA or free fatty acid, ATP and CoASH as an alternative pathway in sphingomyelin biosynthesis has been excluded. Other parameters of the CDP-choline:ceramide cholinephosphotransferase reaction (pH-optimum, ion requirement, competitive inhibition by diacyl glycerols, chain length of fatty acids) are reported. Sphingenine-containing ceramide species are preferred as acceptor molecules. Ceramide species with the L-threo (2S,3S)-enantiomeric long-chain bases are better acceptors than the corresponding D-erythro (2S,3R)-isomeric compounds. The meaning of the steric arrangement for the reaction is discussed.
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002518:Ceramides / Q000096:biosynthesis*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D051381:Rats; D013109:Sphingomyelins / Q000096:biosynthesis* / Q000378:metabolism; D013110:Sphingosine / Q000378:metabolism; D013237:Stereoisomerism; D017855:Transferases (Other Substituted Phosphate Groups)
chemical_list: D000214:Acyl Coenzyme A; D002518:Ceramides; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D003566:Cytidine Diphosphate Choline; D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); C019863:ceramide cholinephosphotransferase; D013110:Sphingosine