Supplemental leucine and isoleucine affect expression of cationic amino acid transporters and myosin, serum concentration of amino acids, and growth performance of pigs

Recent advances have made possible the isolation of the genes and their cDNAs encoding Na(+)-independent amino acid transporters. Two classes of amino acid 'uniporters' have been isolated. One class contains the mCAT (murine cationic amino acid transporter) gene family that encodes proteins predicted to span the membrane 12-14 times and exhibits structural properties similar to the GLUT (glucose transporter) family and to other well-known transporters. The other class consists of two known genes, rBAT (related to B system amino acid transporters) and 4F2hc, that share amino acid sequence similarity with alpha-amylases and alpha-glucosidases. They are type II glycoproteins predicted to span the membrane only once, yet they mediate the Na(+)-independent transport of cationic and zwitterionic amino acids in Xenopus oocytes. Mutations in the human rBAT gene have been identified by Palacín and his co-workers in several families suffering from a heritable form of cystinuria. This important finding clearly establishes a key role for rBAT in cystine transport. The two classes of amino acid transporters are compared with the well-studied GLUT family of Na(+)-independent glucose transporters.

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Transporters for Cationic Amino Acids in Animal Cells: Discovery, Structure, and Function

Physiological Reviews ◽

10.1152/physrev.1998.78.2.487 ◽

1998 ◽

Vol 78 (2) ◽

pp. 487-545 ◽

Cited By ~ 337

Author(s):

R. DEVÉS ◽

C. A. R. BOYD

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Structure And Function ◽

Xenopus Laevis Oocytes ◽

Amino Acid Transporters ◽

Cdna Clones ◽

Animal Cells ◽

Cationic Amino Acid ◽

Cationic Amino Acids ◽

And Function

Devés, R., and C. A. R. Boyd. Transporters for Cationic Amino Acids in Animal Cells: Discovery, Structure, and Function. Physiol. Rev. 78: 487–545, 1998. — The structure and function of the four cationic amino acid transporters identified in animal cells are discussed. The systems differ in specificity, cation dependence, and physiological role. One of them, system y+, is selective for cationic amino acids, whereas the others (B0,+, b0,+, and y+L) also accept neutral amino acids. In recent years, cDNA clones related to these activities have been isolated. Thus two families of proteins have been identified: 1) CAT or cationic amino acid transporters and 2) BAT or broad-scope transport proteins. In the CAT family, three genes encode for four different isoforms [CAT-1, CAT-2A, CAT-2(B) and CAT-3]; these are ∼70-kDa proteins with multiple transmembrane segments ( 12 – 14 ), and despite their structural similarity, they differ in tissue distribution, kinetics, and regulatory properties. System y+is the expression of the activity of CAT transporters. The BAT family includes two isoforms (rBAT and 4F2hc); these are 59- to 78-kDa proteins with one to four membrane-spanning segments, and it has been proposed that these proteins act as transport regulators. The expression of rBAT and 4F2hc induces system b0,+and system y+L activity in Xenopus laevis oocytes, respectively. The roles of these transporters in nutrition, endocrinology, nitric oxide biology, and immunology, as well as in the genetic diseases cystinuria and lysinuric protein intolerance, are reviewed. Experimental strategies, which can be used in the kinetic characterization of coexpressed transporters, are also discussed.

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Coordinated Action of Multiple Transporters in the Acquisition of Essential Cationic Amino Acids by the Intracellular Parasite Toxoplasma gondii

10.1101/2021.06.25.450001 ◽

2021 ◽

Author(s):

Stephen J Fairweather ◽

Esther Rajendran ◽

Martin Blume ◽

Kiran Javed ◽

Birte Steinhoefel ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Toxoplasma Gondii ◽

Large Family ◽

Essential Amino Acids ◽

Amino Acid Transporters ◽

Cationic Amino Acid ◽

Intracellular Parasites ◽

Cationic Amino Acids ◽

High Concentrations

Intracellular parasites of the phylum Apicomplexa are dependent on the scavenging of essential amino acids from their hosts. We previously identified a large family of apicomplexan-specific plasma membrane-localized amino acid transporters, the ApiATs, and showed that the Toxoplasma gondii transporter TgApiAT1 functions in the selective uptake of arginine. TgApiAT1 is essential for parasite virulence, but dispensable for parasite growth in medium containing high concentrations of arginine, indicating the presence of at least one other arginine transporter. Here we identify TgApiAT6-1 as the second arginine transporter. Using a combination of parasite assays and heterologous characterisation of TgApiAT6-1 in Xenopus laevis oocytes, we demonstrate that TgApiAT6-1 is a general cationic amino acid transporter that mediates both the high-affinity uptake of lysine and the low-affinity uptake of arginine. TgApiAT6-1 is the primary lysine transporter in the disease-causing tachyzoite stage of T. gondii and is essential for parasite proliferation. We demonstrate that the uptake of cationic amino acids by TgApiAT6-1 is "trans-stimulated" by cationic and neutral amino acids and is likely promoted by an inwardly negative membrane potential. These findings demonstrate that T. gondii has evolved overlapping transport mechanisms for the uptake of essential cationic amino acids, and we draw together our findings into a comprehensive model that highlights the finely-tuned, regulated processes that mediate cationic amino acid scavenging by these intracellular parasites.

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Transcriptome Analysis and Expression of Selected Cationic Amino Acid Transporters in the Liver of Broiler Chicken Fed Diets with Varying Concentrations of Lysine

International Journal of Molecular Sciences ◽

10.3390/ijms21165594 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5594

Author(s):

Collins N. Khwatenge ◽

Boniface M. Kimathi ◽

Samuel N. Nahashon

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Broiler Chickens ◽

Molecular Mechanisms ◽

Cellular Growth ◽

Control Group ◽

Amino Acid Transporters ◽

Potential Candidate ◽

Cationic Amino Acid ◽

High Lysine

Amino acids are known to play a key role in gene expression regulation. Amino acid signaling is mediated via two pathways: the mammalian target of rapamycin complex 1 (mTORC1) and the amino acid responsive (AAR) pathways. Cationic amino acid transporters (CATs) are crucial in these pathways due to their sensing, signaling and transport functions. The availability of certain amino acids plays a key role in the intake of other amino acids, hence affecting growth in young birds. However, the specific mechanism for regulating lysine transport for growth is not clear. In this study, we analyze the transcriptome profiles and mRNA expression of selected cationic amino acid transporters in the livers of broilers fed low and high lysine diets. Birds consumed high-lysine (1.42% lysine) or low-lysine (0.85% lysine) diets while the control group consumed 1.14% lysine diet. These concentrations of lysine represent 125% (high lysine), 75% (low lysine) and 100% (control), respectively, of the National Research Council’s (NRC) recommendation for broiler chickens. After comparing the two groups, 210 differentially expressed genes (DEGs) were identified (fold change >1 and false discovery rate (FDR) <0.05). When comparing the high lysine and the low lysine treatments, there were 67 upregulated genes and 143 downregulated genes among these DEGs. Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) enrichment analysis show that cellular growth, lipid metabolism and lysine metabolism pathways were among the significantly enriched pathways. This study contributes to a better understanding of the potential molecular mechanisms underlying the correlation between lysine intake, body weight gain (BWG) and feed intake (FI) in broiler chickens. Moreover, the DEGs obtained in this study may be used as potential candidate genes for further investigation of broiler growth customized responses to individualized nutrients such as amino acids.

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The Role of Large Neutral Amino Acid Transporter (LAT1) in Cancer

Current Cancer Drug Targets ◽

10.2174/1568009619666190802135714 ◽

2019 ◽

Vol 19 (11) ◽

pp. 863-876 ◽

Cited By ~ 3

Author(s):

Xinjie Lu

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Metabolic Networks ◽

Amino Acid Transporter ◽

Amino Acid Transporters ◽

Large Neutral Amino Acid ◽

Pharmaceutical Drugs ◽

Cationic Amino Acid ◽

Acid Transporter

Background: The solute carrier family 7 (SLC7) can be categorically divided into two subfamilies, the L-type amino acid transporters (LATs) including SLC7A5-13, and SLC7A15, and the cationic amino acid transporters (CATs) including SLC7A1-4 and SLC7A14. Members of the CAT family transport predominantly cationic amino acids by facilitating diffusion with intracellular substrates. LAT1 (also known as SLC7A5), is defined as a heteromeric amino acid transporter (HAT) interacting with the glycoprotein CD98 (SLC3A2) through a conserved disulfide to uptake not only large neutral amino acids, but also several pharmaceutical drugs to cells. Methods: In this review, we provide an overview of the interaction of the structure-function of LAT1 and its essential role in cancer, specifically, its role at the blood-brain barrier (BBB) to facilitate the transport of thyroid hormones, pharmaceuticals (e.g., I-DOPA, gabapentin), and metabolites into the brain. Results: LAT1 expression increases as cancers progress, leading to higher expression levels in highgrade tumors and metastases. In addition, LAT1 plays a crucial role in cancer-associated reprogrammed metabolic networks by supplying tumor cells with essential amino acids. Conclusion: The increasing understanding of the role of LAT1 in cancer has led to an increase in interest surrounding its potential as a drug target for cancer treatment.

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Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii

PLoS Pathogens ◽

10.1371/journal.ppat.1009835 ◽

2021 ◽

Vol 17 (8) ◽

pp. e1009835

Author(s):

Stephen J. Fairweather ◽

Esther Rajendran ◽

Martin Blume ◽

Kiran Javed ◽

Birte Steinhöfel ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Toxoplasma Gondii ◽

Large Family ◽

Essential Amino Acids ◽

Amino Acid Transporters ◽

Cationic Amino Acid ◽

Intracellular Parasites ◽

Cationic Amino Acids ◽

High Concentrations

Intracellular parasites of the phylum Apicomplexa are dependent on the scavenging of essential amino acids from their hosts. We previously identified a large family of apicomplexan-specific plasma membrane-localized amino acid transporters, the ApiATs, and showed that the Toxoplasma gondii transporter TgApiAT1 functions in the selective uptake of arginine. TgApiAT1 is essential for parasite virulence, but dispensable for parasite growth in medium containing high concentrations of arginine, indicating the presence of at least one other arginine transporter. Here we identify TgApiAT6-1 as the second arginine transporter. Using a combination of parasite assays and heterologous characterisation of TgApiAT6-1 in Xenopus laevis oocytes, we demonstrate that TgApiAT6-1 is a general cationic amino acid transporter that mediates both the high-affinity uptake of lysine and the low-affinity uptake of arginine. TgApiAT6-1 is the primary lysine transporter in the disease-causing tachyzoite stage of T. gondii and is essential for parasite proliferation. We demonstrate that the uptake of cationic amino acids by TgApiAT6-1 is ‘trans-stimulated’ by cationic and neutral amino acids and is likely promoted by an inwardly negative membrane potential. These findings demonstrate that T. gondii has evolved overlapping transport mechanisms for the uptake of essential cationic amino acids, and we draw together our findings into a comprehensive model that highlights the finely-tuned, regulated processes that mediate cationic amino acid scavenging by these intracellular parasites.

Download Full-text