Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

Acute Regulation of the Glycerophospholipid Composition of The Membranes of Mammalian Cells. The First Comprehensive Model

Version 1 : Received: 15 April 2019 / Approved: 19 April 2019 / Online: 19 April 2019 (07:38:21 CEST)
Version 2 : Received: 30 October 2019 / Approved: 31 October 2019 / Online: 31 October 2019 (04:39:47 CET)

A peer-reviewed article of this Preprint also exists.


Is unclear how mammalian cells maintain the complex glycerophospholipid (GPL) compositions of their various membranes. Here we propose the first comprehensive model that suggests how this could be accomplished. The model is based on the idea that there are a limited number of GPL compositions that are energetically more favorable than the other compositions, i.e., those (optimal) compositions represent local free energy minima. Thus, the GPL composition of a membrane has a natural tendency to settle in one of the optimal composition. When the mole fraction of an GPL class exceeds that in an optimal composition, its chemical activity abruptly increases, which (i) increases its propensity to efflux from the membranes thus making it susceptible for hydrolysis by homeostatic phospholipases; (ii) increases its potency to inhibit its own biosynthesis via a feedback mechanism; (iii) enhances its conversion to another GPL class via “head group remodeling” or (iv) enhances its translocation to another membrane. These four processes may act separately or simultaneously to maintain GPL homeostasis.


homeostasis; membrane; glycerophospholipid; composition; chemical activity


Biology and Life Sciences, Biochemistry and Molecular Biology

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