Computational Modeling of Lipid Metabolism in Yeast

Abstract

Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes. Here, we present an object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner. The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

PHGDH supports liver ceramide synthesis and sustains lipid homeostasis

“…For targeted lipidomics, deoxysphingolipid and ceramide peaks identified by MS 2 were manually integrated using the Thermo Xcaliber Qual Browser. The quantification was based on previous methods [11,36]. For nontargeted lipidomics, lipid peaks including triacylglycerols and ceramides were identified, aligned, and exported using MS-DIAL [41].…”

Identification of key lipids critical for platelet activation by comprehensive analysis of the platelet lipidome

“…Quantification of membrane and signaling lipids is clearly required for correct modeling of membrane fluidity, stiffness, or signaling. 21 For a full structural analysis of the lipids, we developed the first comprehensive quantitative lipidomics analysis tailored for murine platelets by providing lipid concentrations of 384 lipid species, spanning 28 lipid classes, monitored in resting and activated platelets. Key findings were confirmed in human platelets.…”

PHGDH supports liver ceramide synthesis and sustains lipid homeostasis

“…For targeted lipidomics, deoxysphingolipid and ceramide peaks identified by MS 2 were manually integrated using Thermo Xcaliber Qual Browser. The quantification was based on previous methods (Esaki et al, 2015; Schutzhold et al, 2016). For non-targeted lipidomics, lipid peaks including triacylglycerols and ceramides were identified, aligned, and exported using MS-DIAL (Tsugawa et al, 2015).…”