Regulation of Hepatic Amino Acid Transport and Partial Purification of the System A Carrier

  • M. S. Kilberg
Conference paper
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)


Amino acid transport across the plasma membrane is an important site for metabolic regulation. Indeed, in many instances transport actually represents the first step of catabolism. Evidence from several laboratories suggests that transport into the hepatocyte is the rate-limiting step for alanine metabolism when tested at physiological levels of the substrate (Christensen, 1983). The general importance of amino acid flows between the major tissues of the body has been reviewed by Christensen (1982). The concept of metabolic control via translocation of nutrients across the plasma membrane is not new; Exton et al. (1970) proposed that substrate supply was a key regulator of amino acid-dependent gluconeogenesis nearly two decades ago. More recently, Christensen (1983) has postulated that concurrent changes in hepatic amino acid metabolism and accumulation ensure that transport across the plasma membrane remains rate-limiting over a wide range of extracellular substrate concentrations. Data from our laboratory indicate that the hepatic utilization of several amino acids for de novo glucose synthesis may be limited by availability.


Amino Acid Transport Plasma Membrane Vesicle Amino Acid Starvation Amino Acid Transport System Dependent Uptake 
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  1. Bracy DS, Handlogten ME, Barber EF, Han H-P, Kilberg MS (1986) Ci s-1nhibition, trans-inhibition, and repression of hepatic amino acid transport mediated by System A. J Biol Chem 261: 1514–1520PubMedGoogle Scholar
  2. Bracy DS, Schenerman MA, Kilberg MS (1987) Solubilization and reconstitution of hepatic System A-mediated amino acid transport. Preparation of proteoliposomes containing glucagon-stimulated transport activity. Biochim Biophys Acta 899: 51–58PubMedCrossRefGoogle Scholar
  3. Christensen HN (1982) Interorgan amino acid nutrition. Physiol Rev 62: 1193–1233PubMedGoogle Scholar
  4. Christensen HN (1983) Hypothesis: Control of hepatic utilization of alanine by membrane transport or by cellular metabolism. Biosci Rep 3: 905–913PubMedCrossRefGoogle Scholar
  5. Edmondson JW, Lumeng L (1980) Biphasic stimulation of amino acid uptake by glucagon in hepatocytes. Biochem Biophys Res Commun 96: 61–68PubMedCrossRefGoogle Scholar
  6. Exton JH, Mallette LE, Jefferson LS, Wong EHA, Friedmann N, Miller TB, Jr, Park CR (1970) The hormonal control of hepatic gluconeogenesis. Recent Prog Horm Res 26: 411–457PubMedGoogle Scholar
  7. Gazzola GC, Dall’Asta V, Guidotti GG (1981) Adaptive regulation of amino acid transport in cultured human fibroblasts. J Biol Chem 2 56: 3191–3198Google Scholar
  8. Kilberg MS (1986) System A-mediated amino acid transport: metabolic control at the plasma membrane. Trends Biochem Sci 11: 183–186CrossRefGoogle Scholar
  9. Kilberg MS, Barber EF, Handlogten ME (1985a) Characteristics and hormonal regulation of amino acid transport System A in isolated rat hepatocytes. Curr Top Cell Regul 25: 133–163PubMedGoogle Scholar
  10. Kilberg MS, Han H-P, Barber E, Chiles TC (1985b) Adaptive regulation of neutral amino acid transport System A in rat H4 hepatoma cells. J Cell Physiol 122: 290–298PubMedCrossRefGoogle Scholar
  11. Kletzien RF, Pariza MW, Becker JE, Potter VR (1975) A “permissive” effect of dexamethasone on the glucagon induction of amino acid transport in cultured hepatocytes. Nature 256: 46–47PubMedCrossRefGoogle Scholar
  12. Oxender DL, Christensen HN (1963) Distinct mediating systems for the transport of neutral amino acids by the Ehrlich cell. J Biol Chem 238: 3686–3699PubMedGoogle Scholar
  13. Prpic V, Green KC, Blackmore PF, Exton JH (1984) Vasopressin, angiotensin II-, and α1-adrenergic-induced inhibition of Ca2+ transport by rat liver plasma membrane vesicles. J Biol Chem 259: 1382–1385PubMedGoogle Scholar
  14. Quinlan DC, Todderud CG, Kelley DS, Kletzien RF (1982) Sodium- gradient-stimulated transport of L-alanine by plasma-membrane vesicles isolated from liver parenchymal cells of fed and starved rats. Biochem J 208: 685–693PubMedGoogle Scholar
  15. Rosenthal NR, Jacob R, Barrett E (1985) Diabetes enhances activity of alanine transport in liver plasma membrane vesicles. Am J Physiol 248: E581–E587PubMedGoogle Scholar
  16. Schenerman MA, Kilberg MS (1986) Maintenance of glucagon- stimulated System A amino acid transport acitivity in rat liver plasma membrane vesicles. Biochim Biophys Acta 856: 428–436PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. S. Kilberg
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Florida School of MedicineGainesvilleUSA

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