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Biochim Biophys Acta. 1995 Apr 28;1256(1):25-30.

Interaction of sphingomyelinase with sphingomyelin analogs modified at the C-1 and C-3 positions of the sphingosine backbone.

Author information

1
Department of Biomolecular Research, Sphinx Pharmaceuticals Corporation, Durham, NC 27717, USA.

Abstract

In this study, analogs differing at the C-1 or C-3 position of the sphingosine backbone of sphingomyelin were examined in neutral pH-optimum sphingomyelinase assays. Two analogs modified at the C-1 position, ceramide-1-phosphate and ceramide-1-phosphoethanol-N,N-dimethylamine, could act as modest substrates but showed no ability to inhibit the reaction when egg sphingomyelin was used as the substrate. Four analogs of sphingomyelin differing at the C-3 position were used in which the hydroxyl group was replaced by a hydrogen atom (to give a deoxy-sphingomyelin analog), or with a O-methyl, O-ethyl or O-tetrahydropyranyl group. The deoxy analog showed no ability to compete with substrate of sphingomyelinase nor could it be hydrolyzed by the enzyme, suggesting that the hydroxyl group is a required substituent for the substrate. The 3-O-methyl and 3-O-ethyl-sphingomyelin analogs were inhibitors, with IC50 values of 50 microM and 140 microM, respectively at standard assay conditions. However, when the rat brain acidic pH-optimum sphingomyelinase was used, no inhibition by the 3-O-methyl analog could be detected. The size of the alkyl group on the ether moiety was important, as shown by the inability of 3-O-tetrahydropyranyl-sphingomyelin to compete with substrate of neutral pH-optimum sphingomyelinase.

PMID:
7742352
DOI:
10.1016/0005-2760(94)00249-x
[Indexed for MEDLINE]

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