The Interactions of Dopamine and L-Dopa with Lipid Headgroup and its Implication for Neurotransmitters Metabolism

Abstract

Atomistic molecular dynamics simulations were used to investigate the interactions between the neurotransmitter dopamine and its precursor L-dopa with membrane lipids. The results indicate that these molecules strongly interact with the lipid head groups e.g. via hydrogen bonds. These interactions anchor the dopamine and L-dopa to the membrane interfacial region. The strength of this bonding is dependent on lipids present in membrane. Presence of phosphatidylserine resulted in increased level of bonding strength with a lifetime longer than the timescale of our simulations.The high membrane association of dopamine and L-dopa both, extracellularly, might favour the availability of these compounds for cell membrane uptake processes and, intracellularly, can accentuate the importance of membrane-bound metabolizing enzymes over their soluble counterparts.We can also hypothesize that excessive association of dopamine and its precursor L-dopa with the membranes in the situation, when the concentration of phosphatidylserine is increased, may eventually limit the free use of dopamine as a synaptic transmitter what could possibly be a molecular level mechanism responsible for some of neurodegenerative disorders.View Large Image | View Hi-Res Image | Download PowerPoint Slide