Physiological, Pharmacological and Toxicological Implications of Heterodimeric Amino Acid Transporters

Kanai, Yoshikatsu,Endou, Hitoshi The Korean Society of Pharmacology 2004 The Korean Journal of Physiology & Pharmacology Vol.8 No.3

The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT $(related\;to\;b^0,\;^+-amino\;acid\;transporter)$. Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters $b^{0,+}AT/BAT1\;(b^{0,+}-type\;amino\;acid\;transporter/b^{0,+}-type\;amino\;acid\;transporter\;1)$ and $y^+LAT1\;(y^+L-type\;amino\;acid\;transporter\;1)$ result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

패혈증 환자에서 혈장 및 적혈구 아미노산의 변화

장순희,조경자,장윤정,송경은,이원길,김재식 대한임상병리학회 1998 대한임상병리학회지 Vol.18 No.2

Amino Acid Imbalance-Biochemical Mechanism and Nutritional Aspects

Park, Byung-Chul Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.9

Amino acid imbalances refer to the deleterious effects that occur when a second-limiting amino acid or mixture of amino acid lacking a particular limiting amino acid is supplemented in diets marginal in one or more indispensable amino acids. In spite of variation in the conditions that have been used to induce amino acid imbalances, such as protein level in the diet, the extent of difference in total nitrogen content between basal and imbalanced diets, and kinds of amino acids used as imbalancing agents, the conspicuous common features of amino acid imbalances have been a decreased concentration of the limiting amino acid in blood, depression of feed intake and weight gain, and increased dietary content of the limiting amino acid needed to correct the imbalances. There is strong evidence that a decrease in the concentration of a limiting amino acid detected in the anterior prepyriform cortex of the brain is followed by behavioral effects, especially a decrease in feed intake. This might be due to the competition between the limiting amino acid and the amino acids in the imbalancing mixture for transport from blood into brain. One of the biochemical responses of animals fed amino acid imbalanced diets is a rapid decrease in the concentration of the limiting amino acid, which are due in part to an increase in catabolism of the limiting amino acid by the increased activities of enzymes involved in the catabolism of the amino acid. Practically, specific amino acid imbalances could be induced in swine and poultry diets that have been supplemented with lysine, methionine, tryptophan when threonine, isoleucine, valine, etc. are potentially third- or fourth-limiting in diets. In these cases supplementation of the limiting amino acid could be beneficial in preventing the decrease of feed intake that could otherwise occur as a result of amino acid imbalance.

Remarkable impact of amino acids on ginsenoside transformation from fresh ginseng to red ginseng

Liu, Zhi,Wen, Xin,Wang, Chong-Zhi,Li, Wei,Huang, Wei-Hua,Xia, Juan,Ruan, Chang-Chun,Yuan, Chun-Su The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.3

Background: Amino acids are one of the major constituents in Panax ginseng, including neutral amino acid, acidic amino acid, and basic amino acid. However, whether these amino acids play a role in ginsenoside conversion during the steaming process has not yet been elucidated. Methods: In the present study, to elucidate the role of amino acids in ginsenoside transformation from fresh ginseng to red ginseng, an amino acids impregnation pretreatment was applied during the steaming process at 120℃. Acidic glutamic acid and basic arginine were used for the acid impregnation treatment during the root steaming. The ginsenosides contents, pH, browning intensity, and free amino acids contents in untreated and amino acid-treated P. ginseng samples were determined. Results: After 2 h of steaming, the concentration of less polar ginsenosides in glutamic acid-treated P. ginseng was significantly higher than that in untreated P. ginseng during the steaming process. However, the less polar ginsenosides in arginine-treated P. ginseng increased slightly. Meanwhile, free amino acids contents in fresh P. ginseng, glutamic acid-treated P. ginseng, and arginine-treated P. ginseng significantly decreased during steaming from 0 to 2h. The pH also decreased in P. ginseng samples at high temperatures. The pH decrease in red ginseng was closely related to the decrease in basic amino acids levels during the steaming process. Conclusion: Amino acids can remarkably affect the acidity of P. ginseng sample by altering the pH value. They were the main influential factors for the ginsenoside transformation. These results are useful in elucidating why and how steaming induces the structural change of ginsenoside inP. ginseng and also provides an effective and green approach to regulate the ginsenoside conversion using amino acids during the steaming process.

Expression and Functional Characterization of Neutral Amino Acid Transporter in HEp2 Human Head and Neck Squamous Cell Carcinoma

Kim, Do Kyung,Yoon, Jung Hoon,Jeon, Jeong Hoon,Lee, Sang Ho Korean Academy of Oral Biology and the UCLA Dental 2004 International Journal of Oral Biology Vol.29 No.2

Amino acid transporters are essential for growth and proliferation in normal and transformed cells. Among the amino acid transport systems, the system L amino acid transporter is a major nutrient transport system responsible for the Na^(+)-independent transport of large neutral amino acids including several essential amino acids. In malignant tumors, a system L transporter L-type amino acid transporter 1 (LAT1) is up-regulated to support tumor cell growth. In this study, we have investigated the expression and functional characterization of system L amino acid transporter in HEp2 human laryngeal squamous cell carcinoma. RT-PCR, real-time quantitative RT-PCR and western blot analysis have revealed that the HEp2 cells express LAT1 together with its associating protein, heavy chain of 4F2 antigen (4F2hc), whereas the HEp2 cells do not express the L-type amino acid transporter 2 (LAT2), the second isoform of system L amino acid transporter. The uptake of [^(14)C]L-leucine by HEp2 cells is Na^(+)-independent and almost completely inhibited by system L amino acid transporter selective inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). The inhibition profile of [^(14)C]L-leucine uptake by various amino acids in the HEp2 cells is comparable with those for the LAT1 expressed in Xenopus oocytes. The majority of [^(14)C]L-leucine uptake is, therefore, mediated by LAT1 in the HEp2 cells. These results suggest that the transport of neutral amino acids including several essential amino acids in the HEp2 human laryngeal squamous cell carcinoma mediated by LAT1. In addition, the specific inhibition of LAT1 in head and neck squamous cell carcinomas will be a new rationale for anti-cancer therapy.

Determination of Amino Acid Composition in Leaf, Stem, and Inflorescence of Alfalfa (Medicago sativa L.)

Karnan Muthusamy,정종성,이배훈,남철환,박형수,최기춘 한국초지조사료학회 2022 한국초지조사료학회지 Vol.42 No.3

Alfalfa is one of the most useful forage crops worldwide, containing a high level of amino acids that are essential to both human and animal health. However, amino acids and their concentrations may differ between plant parts. Hence, detecting amino acids in different plant parts would be useful in the development of diet supplements. The purpose of this study was to determine the amino acid content in alfalfa leaves, stems, and inflorescences using an amino acid analyzer. Asparagine and glutamic acid were the most abundant amino acids found in stems, leaves, and inflorescences than other amino acids. All parts of alfalfa had low concentrations of cysteine and methionine. All amino acids except asparagine were present in the highest concentration in leaves followed by inflorescences. Leaf had a rich amino acid content, namely asparagine, glutamic acid, leucine, proline, and lysine. However, the stem had a lower amino acid composition than the leaf or inflorescence. Overall, the data showed determining the amino acid content of forages provides a good approach to making animal feed with essential and specific amino acids and preventing excessive inclusion of amino acids.

Reabsorption of Neutral Amino Acids Mediated by Amino Acid Transporter LAT2 and TAT1 in The Basolateral Membrane of Proximal Tubule

Park Sun Young,Kim Jong-Keun,Kim In Jin,Choi Bong Kyu,Jung Kyu Yong,Lee Seoul,Park Kyung Jin,Chairoungdua Arthit,Kanai Yoshikatsu,Endou Hitoshi,Kim Do Kyung The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.4

In order to understand the renal reabsorption mechanism of neutral amino acids via amino acid transporters, we have isolated human L-type amino acid transporter 2 (hLAT2) and human T-type amino acid transporter 1 (hTAT1) in human, then, we have examined and compared the gene structures, the functional characterizations and the localization in human kidney. Northern blot analysis showed that hLAT2 mRNA was expressed at high levels in the heart, brain, placenta, kidney, spleen, prostate, testis, ovary, lymph node and the fetal liver. The hTAT1 mRNA was detected at high levels in the heart, placenta, liver, skeletal muscle, kidney, pancreas, spleen, thymus and prostate. Immunohistochemical analysis on the human kidney revealed that the hLAT2 and hTAT1 proteins coexist in the basolateral membrane of the renal proximal tubules. The hLAT2 transports all neutral amino acids and hTAT1 transports aromatic amino acids. The basolateral location of the hLAT2 and hTAT1 proteins in the renal proximal tubule as well as the amino acid transport activity of hLAT2 and hTAT1 suggests that these transporters contribute to the renal reabsorption of neutral and aromatic amino acids in the basolateral domain of epithelial proximal tubule cells, respectively. Therefore, LAT2 and TAT1 play essential roles in the reabsorption of neutral amino acids from the epithelial cells to the blood stream in the kidney. Because LAT2 and TAT1 are essential to the efficient absorption of neutral amino acids from the kidney, their defects might be involved in the pathogenesis of disorders caused by a disruption in amino acid absorption such as blue diaper syndrome.

Influence of biopolymers on the solubility of branched-chain amino acids and stability of their solutions

Hong, Chi Rac,Lee, Gyu Whan,Paik, Hyun-Dong,Chang, Pahn-Shick,Choi, Seung Jun Elsevier 2018 Food chemistry Vol.239 No.-

<P><B>Abstract</B></P> <P>This study confirmed the possibility of biopolymer-type stabilizers to increase the saturation concentration of branched-chain amino acids by preventing their crystallization/precipitation. Although microfluidization increased the initial solubility, it failed to increase the saturation concentration of the branched-chain amino acids. The saturation concentration of the branched-chain amino acids increased from 3.81% to 4.42% and 4.85% after the incorporation of food hydrocolloids and proteins, respectively. However, the branched-chain amino acids:stabilizer ratio did not affect the solubility. In the case of food hydrocolloid-based solutions, crystal formation and growth of branched-chain amino acids occurred during storage, resulting in the precipitation of branched-chain amino acid crystals. However, food proteins effectively increased the stability of the solubilized branched-chain amino acids. The improved solubility and stability of the solubilized branched-chain amino acids could be attributed to interactions between the functional groups (carboxyl, amine, sulfate, aliphatic, aromatic, etc.) of the stabilizer and the branched-chain amino acid molecules.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Microfluidization increased the initial solubility of branched-chain amino acids. </LI> <LI> Stabilizer increased the saturation concentration of branched-chain amino acids. </LI> <LI> Stabilizer type was a main factor to affect the stability of amino acid solutions. </LI> <LI> Amino acid:stabilizer ratio did not affect the BCAA solubility. </LI> <LI> The solution stability was not affected by amino acid:stabilizer ratio. </LI> </UL> </P>

豆乳의 遊離糖 및 Amino Acids 含量分析

崔震相,崔相道,姜君中,朱玉守,南相海,徐源澤 진주산업대학교 농업기술연구소 1998 農業技術硏究所報 Vol.11 No.-

두유의 유리당 및 amino acids의 함량을 HPLC 및 AAA를 이용하여 분석한 결과는 다음과 같다. 시중 유통 두유에서는 단당류중 fructose와 glucose, 이당류중 sucrose, maltose 및 lactose를 분석하였고, sucrose는 0.78∼9.2 mg/mL의 범위로서 모든 시료에서 측정되었다. 17종의 amino acids를 확인하였으며, 그 조성은 모든 시료에서 비슷하였다. Glutamic acid를 비롯한 산성 amino acids가 전체 amino acids의 40.94%로서 가장 많은 함량이었고, threonine을 포함한 필수 amino acids는 31.78%로 측정되었다. Free sugars and amino acids that contained in soybean milk were analyzed with HPLC and AAA(amino acid analyzer), the results were as follows. Fructose and glucose of monosaccharides, and sucrose, maltose and lactose of disaccharides were detected in soybean milk that collected in market. Sucrose was ranged as 0.78∼9.21 mg/mL and showed in all soybean milk. Amino acids were detected 17 varieties, and the compositions were alike in all soybean milk Contents of acidic amino acids including glutamic acid were 40.94% of total amino acids, and the next order was neutral amino acids as 24.62%. Basic amino acids and aromatic amino acids were 10.83% and 9.20%, respectively. Seven varieties of essential amino acids excluding tryptophan analyzed into 31.78% of total amino acds.

가감난간전(加減煖肝煎) 탕약의 아미노산 성분분

이석하 ( Seok Ha Lee ),이채윤 ( Chae Yun Lee ),이성국 ( Seong Guk Lee ),이형환 ( Hyung H Lee ) 한국자연치유학회 2014 Journal of Naturopathy Vol.3 No.2

This study was designed to analyze, using the HPLC method, the quantity and types of amino acids found in the Gagam nanganjeon herbs decoction prescribed to women for treatment of infertility. Eighteen types of L-amino acids were discovered in the 100 g of Gagam Nanganjeon decoction. There were 50 mg of pro, 40 mg of ser, 38.5 mg of arg, 19.6 mg of ala, 14.5 mg of asp and the rest were 13 types of L-amino acid ranging from 0.33~6.2 mg. In the 100 g of Lycium fruit decoction, there were 12 types of amino acids. The quantity of arg was highest with 28 mg, and the rest ranged from 0.125~1.3 mg. Angelica root decoction contained 18 types of amino acids: arg was the most abundant with 71 mg, and the rest ranged from 0.16~5.6 mg. Poria decoction contained 7 types of amino acids: asp was most abundant at 0.5 mg, and the rest ranged from 0.1~0.2 mg. Lindera root decoction contained 14 types of amino acids: ser was most abundant with 6.9 mg, and the rest ranged from 0.14~6.64 mg. Fennel decoction contained 14 types amino acids. Arg was the most abundant at 4.2 mg, and the rest ranged from 0.3~3.2 mg. Cinnamon decoction contained 4 types of amino acids ranging from 0.08~0.37 mg. Costus root decoction contained 15 types of amino acids and it contained especially large amounts of pro at 36 mg, and 0.12~7.8 mg of other amino acids. Evodia decoction contained 14 types of amino acids: large quantity of pro at 11.2 mg, and the rest ranged from 0.19~6.2 mg. Ginger decoction contained 17 types of amino acids: large quantities of ala at 11.2 mg, ser at 10.4 mg, and the rest ranged from 0.06~2.6 mg. Prepared aconite decoction contained small quantities of 4 amino acids. Ginseng decoction contained 12 types of amino acids: large quantities of arg at 27.9% and the rest ranged from 0.12~1.3 mg. In conclusion, we found that each herb in the formula of Gagam nangajnjeon, when combined, contributed 18 amino acids, which assisted in protein and enzyme synthesis necessary for pregnancy. This finding supports the claim that decocting individual herbs do not create the same desired effect as combining herbs in an herbal formula. The particular combination of herbs and the way they react with each other is an important part of understanding the efficacy of this particular prescription.