A MATHEMATICAL-MODEL OF SIALYLATION OF N-LINKED OLIGOSACCHARIDES IN THE TRANS-GOLGI NETWORK

A mathematical model is developed of the compartmentalized sialylation of N-linked oligosaccharides in order to understand and predict the o utcome of sialylation reactions, A set of assumptions are presented, i ncluding Michaelis-Menten-type dependency of reaction rate on the conc entration of the glycoprotein substrate, The resulting model predicts the heterogeneous outcome of a posttranslational oligosaccharide biosy nthesis step, a critical aspect that is not accounted for in the model ing of the cotranslational attachment of oligosaccharides to glycosyla tion sites (Shelikoff ed at, Biotech, Bioeng,, 50, 73-90, 1996) or gen eral models of the secretion process (Noe and Delenick, J, Cell Sci,, 92, 449-459, 1989), In the steady-state for the likely case where the concentration of substrate is much less than the K-m of the sialyltran sferase, the model predicts that the extent of sialylation, x, will de pend upon the enzyme concentration, enzyme kinetic parameters and subs trate residence time in the reaction compartment. The value of x predi cted by the model using available literature data is consistent with t he values of x that have been recently determined for the glycoprotein s CD4 (Spellman et al., Biochemistry, 30, 2395-2406, 1991) and t-PA (S pellman et al,, J, Biol., Chem,, 264, 14100-14111, 1989) secreted by C hinese hamster ovary cells, For the unsaturated case, the model also p redicts that x is independent of the concentration of secreted glycopr otein in the Golgi, The general modeling approach outlined in this art icle may be applicable to other glycosylation reactions and posttransl ational modifications.