Effects of glutamate and aspartate on growth performance, serum amino acids, and amino acid transporters in piglets

The immunosuppressants cyclosporin A, FK506, and rapamycin inhibit growth of unicellular eukaryotic microorganisms and also block activation of T lymphocytes from multicellular eukaryotes. In vitro, these compounds bind and inhibit two different types of peptidyl-prolyl cis-trans isomerases. Cyclosporin A binds cyclophilins, whereas FK506 and rapamycin bind FK506-binding proteins (FKBPs). Cyclophilins and FKBPs are ubiquitous, abundant, and targeted to multiple cellular compartments, and they may fold proteins in vivo. Previously, a 12-kDa cytoplasmic FKBP was shown to be only one of at least two FK506-sensitive targets in the yeast Saccharomyces cerevisiae. We find that a second FK506-sensitive target is required for amino acid import. Amino acid-auxotrophic yeast strains (trp1 his4 leu2) are FK506 sensitive, whereas prototrophic strains (TRP1 his4 leu2, trp1 HIS4 leu2, and trp1 his4 LEU2) are FK506 resistant. Amino acids added exogenously to the growth medium mitigate FK506 toxicity. FK506 induces GCN4 expression, which is normally induced by amino acid starvation. FK506 inhibits transport of tryptophan, histidine, and leucine into yeast cells. Lastly, several genes encoding proteins involved in amino acid import or biosynthesis confer FK506 resistance. These findings demonstrate that FK506 inhibits amino acid import in yeast cells, most likely by inhibiting amino acid transporters. Amino acid transporters are integral membrane proteins which import extracellular amino acids and constitute a protein family sharing 30 to 35% identity, including eight invariant prolines. Thus, the second FK506-sensitive target in yeast cells may be a proline isomerase that plays a role in folding amino acid transporters during transit through the secretory pathway.

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Placental amino acid transport

AJP Cell Physiology ◽

10.1152/ajpcell.1995.268.6.c1321 ◽

1995 ◽

Vol 268 (6) ◽

pp. C1321-C1331 ◽

Cited By ~ 85

Author(s):

A. J. Moe

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Human Placenta ◽

Amino Acid Transport ◽

Single Layer ◽

Maternal Blood ◽

Transport Systems ◽

Amino Acid Transporters ◽

Acid Transport ◽

Principal Mechanism

Normal fetal growth and development depend on a continuous supply of amino acids from the mother to the fetus. The placenta is responsible for the transfer of amino acids between the two circulations. The human placenta is hemomonochorial, meaning that the maternal and fetal circulations are separated by a single layer of polarized epithelium called the syncytiotrophoblast, which is in direct contact with maternal blood. Transport proteins located in the microvillous and basal membranes of the syncytiotrophoblast are the principal mechanism for transfer from maternal blood to fetal blood. Knowledge of the function and regulation of syncytiotrophoblast amino acid transporters is of great importance in understanding the mechanism of placental transport and potentially improving fetal and newborn outcomes. The development of methods for the isolation of microvillous and basal membrane vesicles from human placenta over the past two decades has contributed greatly to this understanding. Now a primary cultured trophoblast model is available to study amino acid transport and regulation as the cells differentiate. The types of amino acid transporters and their distribution between the syncytiotrophoblast microvillous and basal membranes are somewhat unique compared with other polarized epithelia. These differences may reflect the unusual circumstance of this epithelium that is exposed to blood on both sides. The current state of knowledge as to the types of transport systems present in syncytiotrophoblast, their regulation, and the effects of maternal consumption of drugs on transport are discussed.

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Expression of genes coding for selected amino acid transporters in small intestine, liver, and skeletal muscle of pigs fed excess branched-chain amino acids

Genetics and Molecular Research ◽

10.4238/2015.august.19.11 ◽

2015 ◽

Vol 14 (3) ◽

pp. 9779-9792 ◽

Cited By ~ 4

Author(s):

M. Cervantes ◽

N. Arce ◽

H. García ◽

M. Cota ◽

J.K. Htoo ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Small Intestine ◽

Amino Acid ◽

Branched Chain Amino Acids ◽

Amino Acid Transporters ◽

Expression Of Genes ◽

Branched Chain

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Effect of protein restriction on15N transfer from dietary [15N]alanine and [15N]Spirulina platensisinto urea

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.2.e349 ◽

2001 ◽

Vol 281 (2) ◽

pp. E349-E356 ◽

Cited By ~ 2

Author(s):

Mazen J. Hamadeh ◽

L. John Hoffer

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Test Meal ◽

High Protein Diet ◽

Normal Subjects ◽

Insulin Dependent Diabetes Mellitus ◽

Protein Restriction ◽

Dependent Diabetes Mellitus ◽

Serum Amino Acids ◽

Normal Men

Six normal men consumed a mixed test meal while adapted to high (1.5 g · kg−1· day−1) and low (0.3 g · kg−1· day−1) protein intakes. They completed this protocol twice: when the test meals included 3 mg/kg of [15N]alanine ([15N]Ala) and when they included 30 mg/kg of intrinsically labeled [15N] Spirulina platensis([15N]SPI). Six subjects with insulin-dependent diabetes mellitus (IDDM) receiving conventional insulin therapy consumed the test meal with added [15N]Ala while adapted to their customary high-protein diet. Protein restriction increased serum alanine, glycine, glutamine, and methionine concentrations and reduced those of leucine. Whether the previous diet was high or low in protein, there was a similar increase in serum alanine, methionine, and branched-chain amino acid concentrations after the test meal and a similar pattern of15N enrichment in serum amino acids for a given tracer. When [15N]Ala was included in the test meal,15N appeared rapidly in serum alanine and glutamine, to a minor degree in leucine and isoleucine, and not at all in other circulating amino acids. With [15N]SPI, there was a slow appearance of the label in all serum amino acids analyzed. Despite the different serum amino acid labeling, protein restriction reduced the postmeal transfer of dietary15N in [15N]Ala or [15N]SPI into [15N]urea by similar amounts (38 and 43%, respectively, not significant). The response of the subjects with IDDM was similar to that of the normal subjects. Information about adaptive reductions in dietary amino acid catabolism obtained by adding [15N]Ala to a test meal appears to be equivalent to that obtained using an intrinsically labeled protein tracer.

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PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids

Development ◽

10.1242/dev.01821 ◽

2005 ◽

Vol 132 (10) ◽

pp. 2365-2375 ◽

Cited By ~ 99

Author(s):

D. C. I. Goberdhan

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Amino Acid Transporters ◽

Related Amino Acid ◽

Bulk Transport

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Rhizobium leguminosarum Has a Second General Amino Acid Permease with Unusually Broad Substrate Specificity and High Similarity to Branched-Chain Amino Acid Transporters (Bra/LIV) of the ABC Family

Journal of Bacteriology ◽

10.1128/jb.184.15.4071-4080.2002 ◽

2002 ◽

Vol 184 (15) ◽

pp. 4071-4080 ◽

Cited By ~ 76

Author(s):

A. H. F. Hosie ◽

D. Allaway ◽

C. S. Galloway ◽

H. A. Dunsby ◽

P. S. Poole

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Rhizobium Leguminosarum ◽

Binding Protein ◽

Amino Acid Transporters ◽

Acid Uptake ◽

Amino Acid Permease ◽

Branched Chain Amino Acid ◽

General Amino Acid Permease ◽

Branched Chain

ABSTRACT Amino acid uptake by Rhizobium leguminosarum is dominated by two ABC transporters, the general amino acid permease (Aap) and the branched-chain amino acid permease (BraRl). Characterization of the solute specificity of BraRl shows it to be the second general amino acid permease of R. leguminosarum. Although BraRl has high sequence identity to members of the family of hydrophobic amino acid transporters (HAAT), it transports a broad range of solutes, including acidic and basic polar amino acids (l-glutamate, l-arginine, and l-histidine), in addition to neutral amino acids (l-alanine and l-leucine). While amino and carboxyl groups are required for transport, solutes do not have to be α-amino acids. Consistent with this, BraRl is the first ABC transporter to be shown to transport γ-aminobutyric acid (GABA). All previously identified bacterial GABA transporters are secondary carriers of the amino acid-polyamine-organocation (APC) superfamily. Also, transport by BraRl does not appear to be stereospecific as d amino acids cause significant inhibition of uptake of l-glutamate and l-leucine. Unlike all other solutes tested, l-alanine uptake is not dependent on solute binding protein BraCRl. Therefore, a second, unidentified solute binding protein may interact with the BraDEFGRl membrane complex during l-alanine uptake. Overall, the data indicate that BraRl is a general amino acid permease of the HAAT family. Furthermore, BraRl has the broadest solute specificity of any characterized bacterial amino acid transporter.

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Na(+)-independent transport (uniport) of amino acids and glucose in mammalian cells.

Journal of Experimental Biology ◽

10.1242/jeb.196.1.93 ◽

1994 ◽

Vol 196 (1) ◽

pp. 93-108

Author(s):

D K Kakuda ◽

C L MacLeod

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Mammalian Cells ◽

Glucose Transporter ◽

Sequence Similarity ◽

Amino Acid Sequence Similarity ◽

Amino Acid Transporters ◽

Cationic Amino Acid ◽

Transporter Family ◽

Share Amino Acid Sequence

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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