Modulation of membrane transport by free fatty acids: inhibition of synaptosomal sodium-dependent amino acid uptake

Abstract

High-affinity, Na+-dependent synaptosomal amino acid uptake systems are strongly stimulated by proteins which are known to bind free fatty acids. The rate of uptake as well as the overall level of accumulation is increased by such proteins as bovine serum albumin, hepatic fatty acid binding protein, beta-lactoglobulin, and fetuin. Such a stimulation is not observed with proteins which do not bind fatty acids. The transport activity of synaptosomal preparations can be directly correlated with the free fatty acid content of the preparation. Thus, incubation with albumin reduces the free fatty acid content of synaptosomal preparations, suggesting that the stimulatory effects of the proteins are related to their removal of inhibitory fatty acids formed by hydrolysis of membrane lipids during incubation. Inhibition of amino acid uptake is seen with most cis-unsaturated long chain fatty acids while saturated and trans-unsaturated fatty acids have relatively little or no effect. Under conditions in which the ionophore gramicidin D causes an increase of 22Na flux into synaptosomes, oleic acid (50 microM) has no effect on the influx. These data are consistent with the hypothesis proposed earlier by us [Rhoads, D. E., Peterson, N. A., & Raghupathy, E. (1982) Biochemistry 21, 4782] that Na+-dependent amino acid transport carrier proteins reside in a relatively fluid lipid domain in the synaptosomal membrane and that the effects of cis-unsaturated fatty acids are mediated by interactions with such domains.

High Sensitivity of Glutamate Uptake to Extracellular Free Arachidonic Acid Levels in Rat Cortical Synaptosomes and Astrocytes

“…This result is in agreement with Barbour et al ( 1989), whereas other investigators need higher arachidonate concentrations (250 p M ) (see Lynch and Voss, 1990). Cis-polyunsaturated fatty acids, but not trans-unsaturated and saturated ones, mimic arachidonate inhibition (Rhoads et al, 1983;Barbour et al, 1989;Volterra et al, 1992), suggesting that the relevant molecular feature for this effect is the folded carbon chain of arachidonic acid and its analogues. We find also that the melittin effect is insensitive to indometh- acin.…”

Membrane docosahexaenoate is supplied to the developing brain and retina by the liver.

“…Loss of 22:6 in neurodegenerative disorders and aging may result from a failure in the replenishment system. A number of mechanisms conceivably contribute to maintaining 22:6 levels in tissues, such as cellular (27,28) and extracellular matrix fatty acid-binding proteins (29), docosahexaenoyl-coenzyme A synthetase (5-7), and likely a relative enrichment in receptors (fatty acid-binding proteins for uptake of 22:6) that allows brain and retina (including choriocapillaries and retinal pigment epithelium) to take up 22:6 from serum carriers. A putative 22:6 receptor could explain why the central nervous system contains much higher quantities of 22:6 than other tissues, despite being exposed to similar levels of 22:6 circulating in the blood.…”

Transport, metabolism and distribution space of octanoate in the perfused rat liver

“…These possibilities become more plausible if one remembers that free fatty acids with low melting temperatures, when introduced into membranes, usually increasē uidity. 21 In the case of octanoate this is a striking possibility because it is liquid at 378C.…”