Characteristics of taurine transport in rat liver lysosomes

Abstract

Taurine (2-aminoethanesulfonic acid) is a unique sulfur amino acid derivative that has putative nutritional, osmoregulatory, and neuroregulatory roles and is highly concentrated within a variety of cells. The permeability of Percoll density gradient purified rat liver lysosomes to taurine was examined. Intralysosomal amino acid analysis showed trace levels of taurine compared to most other amino acids. Taurine uptake was Na(+)-independent, with an overshoot between 5-10 minutes. Trichloroacetic acid extraction studies and detergent lysis confirmed that free taurine accumulated in the lysosomal space. Kinetic studies revealed heterogeneous uptake with values for Km1 = 31 +/- 1.82 and Km2 greater than 198 +/- 10.2 mM. The uptake had a pH optimal of 6.5 and was stimulated by the potassium specific ionophore valinomycin. The exodus rate was fairly rapid, with a t1/2 of 5 minutes at 37 degrees C. Analog inhibition studies indicated substrate specificity similar to the plasma membrane beta-alanine carrier system, with inhibition by beta-alanine, hypotaurine, and taurine. alpha-Alanine, 2-methylaminoisobutyric acid (MeAIB), and threonine were poor inhibitors. No effects were observed with sucrose and the photoaffinity derivative of taurine NAP-taurine [N-(4-azido-2-nitrophenyl)-2-aminoethanesulfonate]. In summary, rat liver lysosomes possess a high Km system for taurine transport that is sensitive to changes in K+ gradient and perhaps valinomycin induced diffusional membrane potential. These features may enable lysosomes to adapt to changing intracellular concentrations of this osmotic regulatory substance.

Identification and characterization of a lysosomal transporter for small neutral amino acids

“…Taken together, these data support a physiological role of LYAAT-1 as an amino acid transporter involved in the efflux of lysosomal proteolysis products, such as L-proline, L-alanine, or glycine, from the organelle lumen to the cytosol. Each of these amino acids is present at a Ϸ50 M concentration in the lumen of liver lysosomes (24), thus amounting to an overall substrate concentration of 150 M, which is in good agreement with a K m value of Ϸ500 M (Fig. 3 d and e).…”

Epithelia & Membrane Transport

“…The human leukaemic cell line K562 can be induced to differentiate by various mutagens, and has been used to study expression e.g. of globin genes (Cioe et al 1981), and amino acid transport systems (Vadgama et al 1991). We have investigated the possibility of inducing the Caactivated K channel in these cells, following treatment with haemin.…”

Influence of membrane physical state on lysosomal potassium ion permeability

“…As established previously, some lysosomal transport systems are sensitive to the movement of K C across their membranes. The lysosomal uptake of taurine (a sulfur amino acid derivative that has putative nutritional, osmoregulatory and neuroregulatory roles in a variety of cells) can be enhanced by the influx of K C , which changes the cytoplasmic concentration of taurine (Vadgama et al, 1991). Cystinosis is a recessively inherited metabolic disorder characterized by intralysosomal cystine storage (due to a deficiency in lysosomal cystine transport) (Pisoni and Thoene, 1991).…”