L-type amino acid transporter

Uchino, H., et al. Transport of amino add-related compounds mediated by L-type amino acid transporter 1 (LAT1) insights into the mechanisms of substrate recognition. Mol. Pharmacol. 2002, 61, 729—737. 

Immunohistochemical study ND not determined GLUT1 facilitative glucose transporter MCT1 monocarboxylate transporter CRT creatine transporter LAT1 L-type amino acid transporter TAUT taurine transporter ENT equilibrative nucleoside transporter Oatp organic anion-transporting polypeptide PAH p-aminohippuric acid RUI retinal uptake index TR-iBRB rat retinal capillary endothelial cells. 

M. Tomi, M. Mori, M. Tachikawa, K. Katayama, T. Terasaki, and K. Hosoya. L-Type amino acid transporter 1 (LATl)-mediated L-leucine transport at the inner blood-retinal barrier. Invest. Ophthalmol. Vis. Sci. 46 2522-2530... 

Fig. 11 Labeled artificial amino acids which were recognized by the L-type amino acid transporter LAT1 (36) whereas the isomer 37 lost any affinity...

MRP2 (Fig. 14.6) [34, 63]. In addition, 2 suppresses L-type amino acid transporter 1 and Na /glucose cotransporter 1 transporter s function through the release of their transporters from the apical membranes of Caco-2R cell monolayers. Interestingly, DM-a-CyD augments H -coupled peptide transporter PepTl-mediated uptake of glycylsarcosine in Caco-2 and Caco-2R cell monolayers. 

The main factor for the increased uptake of radiolabeled amino acids in malignant tumors appears to be the increased expression and activity of the so-called L-type amino acid transporter. This transport system mediates the movement of neutral amino acids across the cell membrane. It has long been characterized as a nonenergy-dependent bidirectional transport system, which... 

Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, Cha SH, Matsuo H, Fukushima J, Eukasawa Y, Tani Y, Taketani Y, Uchino H, Kim JY, Inatomi J, Okayasu I, Miyamoto K, Takeda E, Goya T, Endou H. Human L-type amino acid transporter 1 (LATl) characterization of fimction and expression in tumor cell lines. Biochim Biophys Acta 2001 1514 291 302. 

Abstract Polyamine (PA) transport has been analyzed at the ceU and organ levels in several plant species, but currently the molecular mechanisms of PA transport are not completely understood. Several papers recently identified plant PA transporters. A study of Arabidopsis oxidative stress responses to the herbicide paraquat (PQ) identified a LAT (L-type amino acid transporter) family protein as a transporter of both PQ and PA. Other studies based on yeast complementation analyses revealed that LAT family genes in rice md Arabidopsis function as PA transporters. 

Simmons-Willis, T. A., et al. Transport of a neurotoxicant by molecular mimicry the methylmercury-l-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. Biochem. J. 2002, 367, 239-246. 

Lavillette, D., Marin, M., Ruggierei, A., Mallet, F., Cosset, F.-L. and Kahat, D. (2002) The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters / cell surface receptors. J Viroll, 6442-6452. 

It is apparent that at this stage of development definitive conclusions are premature, and that this aspect of amino acid and lipide metabolism will be pursued vigorously in the near future. It is of considerable interest to us that biotin and pantothenic acid deficiencies affect amino acid transport in L. arabinosus, since both vitamins are known to play a prominent role in lipide biosynthesis. We are currently reexamining the turnover of lipide fractions in nutritionally normal and vitamin-deficient cell types to determine whether there is some relation between this aspect of metabolism and amino acid transport. In any case, the nature of the catalytic steps involved in amino acid transport is still unknown to us. They probably occur in the peripheral cell membrane, but even this elementary and widely accepted belief will require additional study before it can be accepted beyond doubt as an established fact. 

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

FIGURE 23.7 Dopamine (DA) is synthesized within neuronal terminals from the precursor tyrosine by the sequential actions of the enzymes tyrosine hydroxylase, producing the intermediary L-dihydroxyphenylalanine (Dopa), and aromatic L-amino acid decarboxylase. In the terminal, dopamine is transported into storage vesicles by a transporter protein (T) associated with the vesicular membrane. Release, triggered by depolarization and entry of Ca2+, allows dopamine to act on postsynaptic dopamine receptors (DAR). Several distinct types of dopamine receptors are present in the brain, and the differential actions of dopamine on postsynaptic targets bearing different types of dopamine receptors have important implications for the function of neural circuits. The actions of dopamine are terminated by the sequential actions of the enzymes catechol-O-methyl-transferase (COMT) and monoamine oxidase (MAO), or by reuptake of dopamine into the terminal. 

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