Modeling sphingomyelin synthase 1 driven reaction at the Golgi apparatus can explain data by inclusion of a positive feedback mechanism

Abstract

Here we present a minimal mathematical model for the sphingomyelin synthase 1 (SMS1) driven conversion of ceramide to sphingomyelin based on chemical reaction kinetics. We demonstrate via mathematical analysis that this model is not able to qualitatively reproduce experimental measurements on lipid compositions after altering SMS1 activity. We prove that a positive feedback mechanism from the products to the reactants of the reaction is one possible model extension to explain these specific experimental data. The proposed mechanism in fact exists in vivo via protein kinase D and the ceramide transfer protein CERT. The model is further evaluated by additional observations from the literature.

Keywords: CHO Cells; Cer; Chinese hamster ovary cells; DAG; ER; Feedback control; IFT; PC; PH Domain; PI; PI4KIIIβ; PI4P; PKD; SM; SMS; Sphingomyelin synthase 1; Sphingomyelin synthesis; TGN; ceramide; diacylglycerol; endoplasmic Reticulum; implicit function theorem; phosphatidylcholine; phosphatidylinositol; phosphatidylinositol(4)-Phosphat; phosphatidylinositol-4-Kinase IIIβ; pleckstrin homology domain; protein kinase D; sphingomyelin; sphingomyelin synthase; trans-Golgi network.