Authors; Lucia Sessa, Anna Maria Nardiello, Jacopo Santoro, Simona Concilio, and Stefano Piotto.
Title: Hydroxylated Fatty Acids: The Role of the Sphingomyelin Synthase and the Origin of Selectivity.
Journal: Membranes (Basel)
2021 Oct; 11(10): 787. Published online 2021 Oct 16.
Abstract; Sphingolipids are a class of lipids acting as key modulators of many physiological and pathophysiological processes. Hydroxylation patterns have a major influence on the biophysical properties of sphingolipids. In this work, we have studied the mechanism of action of hydroxylated lipids in sphingomyelin synthase (SMS). The structures of the two human isoforms, SMS1 and SMS2, have been generated through neural network supported homology. Furthermore, we have elucidated the reaction mechanism that allows SMS to recover the choline head from a phosphocholine (PC) and transfer it to ceramide, and we have clarified the role of the hydroxyl group in the interaction with the enzyme. Finally, the effect of partial inhibition of SMS on the levels of PC and sphingomyelin was calculated for different rate constants solving ordinary differential equation systems