Strong preferences of dopamine and l -dopa towards lipid head group: Importance of lipid composition and implication for neurotransmitter metabolism

Abstract

The interactions of the neurotransmitter dopamine, and its precursor l-dopa, with membrane lipids were investigated through a set of molecular dynamic simulations with all atom resolution. The results obtained indicate that both dopamine and l-dopa have a pronounced association with the lipid head groups, predominantly mediated through H-bonds. As a result the molecules are anchored to the interfacial region of the membrane. The strength of this interaction is dependent on lipid composition - the presence of phosphatidylserine leads to an increase in the strength of this interaction, resulting in an H-bond network with a lifetime much longer than the timescale of our simulations. Also, bilayers that include sphingomieline and cholesterol interact strongly with dopamine and l-dopa. We postulate that the high membrane association that we have observed for both dopamine and l-dopa could have the following effects: 1) when on the plasma membrane exterior, favour the availability of these compounds for cell membrane uptake processes and, 2) when on an internal membrane surface, accentuate the importance of membrane-bound metabolizing enzymes over their soluble counterparts. Through a computational study, we have shown that both dopamine and l-dopa have a pronounced association with lipid membrane head groups, predominantly mediated through a network of H-bonds. As a result, the molecules are anchored to the interfacial region of the membrane. The strength of this interaction is dependent on lipid composition. Possible effects for the metabolism of dopamine are discussed. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.