Strong preferences of dopamine and l-dopa towards lipid head group: importance of lipid composition and implication for neurotransmitter metabolism.
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.
Department of Physics, Tampere University of Technology, Finland.
Adam
A
Orłowski
Michał
M
Grzybek
Alex
A
Bunker
Marta
M
Pasenkiewicz-Gierula
Ilpo
I
Vattulainen
Pekka T
PT
Männistö
Tomasz
T
Róg
D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004298:Dopamine / Q000737:chemistry* / Q000378:metabolism; D015259:Dopamine Agents / Q000737:chemistry*; D006860:Hydrogen Bonding; D007980:Levodopa / Q000737:chemistry*; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D055672:Static Electricity
D015259:Dopamine Agents; D008051:Lipid Bilayers; D008055:Lipids; D018377:Neurotransmitter Agents; D010718:Phosphatidylserines; D007980:Levodopa; D004298:Dopamine