Free fatty acids inhibit an ion-coupled membrane transporter by dissipating the ion gradient.

ABSTRACT: Glutamate is the main excitatory transmitter in the mammalian central nervous system; glutamate transporters keep the synaptic glutamate concentrations at bay for normal brain function. Arachidonic acid (AA), docosahexaenoic acid, and other unsaturated fatty acids modulate glutamate transporters in cell- and tissue slices-based studies. Here, we investigated their effect and mechanism using a purified archaeal glutamate transporter homolog reconstituted into the lipid membranes. AA, docosahexaenoic acid, and related fatty acids irreversibly inhibited the sodium-dependent concentrative substrate uptake into lipid vesicles within the physiologically relevant concentration range. In contrast, AA did not inhibit amino acid exchange across the membrane. The length and unsaturation of the alipha

SUBMITTER: Wang X 

PROVIDER: S-EPMC11667161 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature