Plasma‐membrane transport of alanine is rate‐limiting for its metabolism in rat‐liver parenchymal cells

Sips, Herman J.; Groen, Albert K.; Tager, J. M.

doi:10.1016/0014-5793(80)80269-9

Cited by 83 publications

(24 citation statements)

References 16 publications

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“…The well-documented induction of System A amino acid transport following PH [12,26] and exposure to glucagon [4,19] and during movement into the cell cycle [3,9] are examples of up-regulated amino acid transport presumably providing increased nutrition for regeneration, substrate for gluconeogenesis, and macromolecule precursors for cell proliferation, respectively. The difference in transport rate, and the resulting cytoplasmic availability of substrate [37], could regulate some of the processes fueled by System A transport activity. However, characterization of these amino acid transport systems at the molecular level is in its infancy, and the future unraveling of the role that each System A component plays in liver regeneration will enhance the understanding of this unique phenomenon.…”

Section: Discussionmentioning

confidence: 99%

ATA2-mediated amino acid uptake following partial hepatectomy is regulated by redistribution to the plasma membrane

Freeman

Thiele

Tuma

et al. 2002

Archives of Biochemistry and Biophysics

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Section: Discussionmentioning

confidence: 99%

ATA2-mediated amino acid uptake following partial hepatectomy is regulated by redistribution to the plasma membrane

Freeman

Thiele

Tuma

et al. 2002

Archives of Biochemistry and Biophysics

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“…These studies were performed in perifused hepatocytes from both fed and fasted rats using physiological concentrations of alanine (0.2 to 0.5 mM). McGivan, Ramsell and Lacey (1981) extended the work of Sips et al (1980) to show that at alanine concentrations greater than 1 mM translocation of alanine across the plasma membrane was not metabolically rate-limiting. Furthermore, it was concluded that stimulation of alanine metabolism by exogenous cAMP could be limited by the rate of alanine transport at physiological levels of the amino acid, although the primary effect of the cAMP occurred on an intracellular reaction when the alanine concentration was above 1 mN (McGivan et al, 1981).…”

mentioning

confidence: 95%

“…With respect to regulation of amino acid-dependent gluconeogenesis, it has long been recognized that amino acid supply may provide a control point in the overall process (Exton, Mallette, Jefferson, Wong, Friedmann, Miller & Park, 1970). Recently, it was shown that transport of ai[anine into isolated rat hepatocytes represents the rate-limiting step in alanine metabolism (Sips, Groen & Tager, 1980). These studies were performed in perifused hepatocytes from both fed and fasted rats using physiological concentrations of alanine (0.2 to 0.5 mM).…”

mentioning

confidence: 98%

Amino acid transport in isolated rat hepatocytes

Kilberg

1982

J. Membrain Biol.

217

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Improvements in the collagenase perfusion techniques have made isolated rat hepatocytes a popular model in which to study hepatic function. Our knowledge of hepatic amino acid transport has been advanced as a result of this methodology. Translocation across the hepatocyte plasma membrane can, in some instances, represent the rate-limiting step in the overall metabolism of certain amino acids. Furthermore, regulation of amino acid uptake by hepatocytes appears to play a role in diabetes, and perhaps in malignant transformation. Comparisons between normal adult hepatocytes and several hepatoma cell lines show basic differences in amino acid transport. There are at least eight distinct systems in normal hepatocytes for transport of the hormones. Systems A and N exhibit enhanced uptake rates after the cells have been maintained in the absence of extracellular amino acids, a phenomenon termed adaptive control. Further studies using isolated hepatocytes will increase our basic understanding of membrane transport processes and their regulation.

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“…Regulation of transport activity has been investigated extensively and is increased by a broad spectrum of hormones and growth factors as well as substrate availability and cellular growth rate (15,62,81,89). Hepatic transport of alanine, in part mediated by System A activity, can be a rate-determining step for further alanine metabolism (27,28), and thus it is hypothesized that glucagon-induced alanine delivery via System A contributes to the aberrant synthesis of glucose in diabetes (106). In addition to hormone signals, System A transport activity is increased by amino acid limitation.…”

Section: Snat2 Neutral Amino Acid Transporter-systemmentioning

confidence: 99%

NUTRITIONAL CONTROL OF GENE EXPRESSION: How Mammalian Cells Respond to Amino Acid Limitation

et al. 2005

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The amino acid response (AAR) pathway in mammalian cells is designed to detect and respond to amino acid deficiency. Limiting any essential amino acid initiates this signaling cascade, which leads to increased translation of a "master regulator," activating transcription factor (ATF) 4, and ultimately, to regulation of many steps along the pathway of DNA to RNA to protein. These regulated events include chromatin remodeling, RNA splicing, nuclear RNA export, mRNA stabilization, and translational control. Proteins that are increased in their expression as targets of the AAR pathway include membrane transporters, transcription factors from the basic region/ leucine zipper (bZIP) superfamily, growth factors, and metabolic enzymes. Significant progress has been achieved in understanding the molecular mechanisms by which amino acids control the synthesis and turnover of mRNA and protein. Beyond gaining additional knowledge of these important regulatory pathways, further characterization of how these processes contribute to the pathology of various disease states represents an interesting aspect of future research in molecular nutrition.Keywords nutrient starvation; metabolite control; protein metabolism; transcription; mRNA stability * ABBREVIATIONS: AAR, amino acid response (pathway); AARE, amino acid response element; ARE, AU-rich elements; ASNS, asparagine synthetase; Cdk, cyclin-dependent kinase; CdkI, cyclin-dependent kinase inhibitor; C/EBP, CCAAT-enhancer binding protein; ChIP, chromatin immunoprecipitation; CHOP, C/EBP homology protein/growth arrest and DNA damage 153; EMSA, electrophoresis mobility shift analysis; mTOR, mammalian target of rapamycin; NSRE, nutrient-sensing response element; UPR, unfolded protein response.

show abstract

Plasma‐membrane transport of alanine is rate‐limiting for its metabolism in rat‐liver parenchymal cells

Cited by 83 publications

References 16 publications

ATA2-mediated amino acid uptake following partial hepatectomy is regulated by redistribution to the plasma membrane

ATA2-mediated amino acid uptake following partial hepatectomy is regulated by redistribution to the plasma membrane

Amino acid transport in isolated rat hepatocytes

NUTRITIONAL CONTROL OF GENE EXPRESSION: How Mammalian Cells Respond to Amino Acid Limitation

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