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. 1972 Aug;51(8):2130–2142. doi: 10.1172/JCI107020

Transport of dibasic amino acids, cystine, and tryptophan by cultured human fibroblasts: absence of a defect in cystinuria and Hartnup disease

Ulrich Groth 1,2, Leon E Rosenberg 1,2
PMCID: PMC292370  PMID: 5054467

Abstract

Transport of lysine, arginine, cystine, and tryptophan was studied in cultured skin fibroblasts from normal controls and from patients with cystinuria and Hartnup disease. Each of these amino acids was accumulated against concentration gradients by energy-dependent, saturable mechanisms. Lysine and arginine were each transported by two distinct processes which they shared with each other and with ornithine. In contrast, cystine was taken up by a different transport system with no demonstrable affinity for the dibasic amino acids. The time course and Michaelis-Menten kinetics of lysine and cystine uptake by cells from three cystinuric patients differed in no way from those found in control cells. Similarly, the characteristics of tryptophan uptake by cells from a child with Hartnup disease were identical to those noted in control cells. These findings indicate that the specific transport defects observed in gut and kidney in cystinuria and Hartnup disease are not expressed in cultured human fibroblasts, thus providing additional evidence of the important role that cellular differentiation plays in the regulation of expression of the human genome.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AKEDO H., CHRISTENSEN H. N. Nature of insulin action on amino acid uptake by the isolated diaphragm. J Biol Chem. 1962 Jan;237:118–122. [PubMed] [Google Scholar]
  2. AMES G. F. UPTAKE OF AMINO ACIDS BY SALMONELLA TYPHIMURIUM. Arch Biochem Biophys. 1964 Jan;104:1–18. doi: 10.1016/s0003-9861(64)80028-x. [DOI] [PubMed] [Google Scholar]
  3. ARROW V. K., WESTALL R. G. Amino acid clearances in cystinuria. J Physiol. 1958 Jun 18;142(1):141–146. doi: 10.1113/jphysiol.1958.sp006004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BECKER F. F., GREEN H. Incorporation of cystine and lysine by normal and cystinuric leukocytes. Proc Soc Exp Biol Med. 1958 Dec;99(3):694–696. doi: 10.3181/00379727-99-24466. [DOI] [PubMed] [Google Scholar]
  5. CHRISTENSEN H. N. A TRANSPORT SYSTEM SERVING FOR MONO- AND DIAMINO ACIDS. Proc Natl Acad Sci U S A. 1964 Feb;51:337–344. doi: 10.1073/pnas.51.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Curran P. F., Schultz S. G., Chez R. A., Fuisz R. E. Kinetic relations of the Na-amino acid interaction at the mucosal border of intestine. J Gen Physiol. 1967 May;50(5):1261–1286. doi: 10.1085/jgp.50.5.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FOX M., THIER S., ROSENBERG L., KISER W., SEGAL S. EVIDENCE AGAINST A SINGLE RENAL TRANSPORT DEFECT IN CYSTINURIA. N Engl J Med. 1964 Mar 12;270:556–561. doi: 10.1056/NEJM196403122701105. [DOI] [PubMed] [Google Scholar]
  8. Grenson M., Mousset M., Wiame J. M., Bechet J. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. I. Evidence for a specific arginine-transporting system. Biochim Biophys Acta. 1966 Oct 31;127(2):325–338. doi: 10.1016/0304-4165(66)90387-4. [DOI] [PubMed] [Google Scholar]
  9. Hillman R. E., Albrecht I., Rosenberg L. E. Identification and analysis of multiple glycine transport systems in isolated mammalian renal tubules. J Biol Chem. 1968 Nov 10;243(21):5566–5571. [PubMed] [Google Scholar]
  10. Hillman R. E., Rosenberg L. E. Amino acid transport by isolated mammalian renal tubules. II. Transport systems for L-proline. J Biol Chem. 1969 Aug 25;244(16):4494–4498. [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Mahoney M. J., Rosenberg L. E. Uptake of alpha-aminoisobutyric acid by cultured human fibroblasts. Biochim Biophys Acta. 1970 Dec 1;219(2):500–502. doi: 10.1016/0005-2736(70)90232-4. [DOI] [PubMed] [Google Scholar]
  13. Matthews R. H., Leslie C. A., Scholefield P. G. Histidine uptake and exchange in S 37 ascites tumor cells. Biochim Biophys Acta. 1970 Jun 2;203(3):457–463. doi: 10.1016/0005-2736(70)90185-9. [DOI] [PubMed] [Google Scholar]
  14. Mellman W. J. A biochemical genetic view of human cell culture. Adv Hum Genet. 1971;2:259–306. [PubMed] [Google Scholar]
  15. Milne M. D., Asatoor A. M., Edwards K. D., Loughridge L. W. The intestinal absorption defect in cystinuria. Gut. 1961 Dec;2(4):323–337. doi: 10.1136/gut.2.4.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Munck B. G. Interactions between lysine, Na+ and Cl- transport in rat jejunum. Biochim Biophys Acta. 1970 Jun 2;203(3):424–433. doi: 10.1016/0005-2736(70)90182-3. [DOI] [PubMed] [Google Scholar]
  17. OXENDER D. L., CHRISTENSEN H. N. DISTINCT MEDIATING SYSTEMS FOR THE TRANSPORT OF NEUTRAL AMINO ACIDS BY THE EHRLICH CELL. J Biol Chem. 1963 Nov;238:3686–3699. [PubMed] [Google Scholar]
  18. Pardee A. B. Membrane transport proteins. Proteins that appear to be parts of membrane transport systems are being isolated and characterized. Science. 1968 Nov 8;162(3854):632–637. doi: 10.1126/science.162.3854.632. [DOI] [PubMed] [Google Scholar]
  19. ROBSON E. B., ROSE G. A. The effect of intravenous lysine on the renal clearances of cystine, arginine and ornithine in normal subjects, in patients with cystinuria and Fanconi syndrome and in their relatives. Clin Sci. 1957 Feb;16(1):75–93. [PubMed] [Google Scholar]
  20. ROSENBERG L. E., DOWNING S. J., SEGAL S. Competitive inhibition of dibasic amino acid transport in rat kidney. J Biol Chem. 1962 Jul;237:2265–2270. [PubMed] [Google Scholar]
  21. ROSENBERG L. E., DOWNING S. TRANSPORT OF NEUTRAL AND DIBASIC AMINO ACIDS BY HUMAN LEUKOCYTES: ABSENCE OF DEFECT IN CYSTINURIA. J Clin Invest. 1965 Aug;44:1382–1393. doi: 10.1172/JCI105243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reiser S., Christiansen P. A. The properties of the preferential uptake of L-leucine by isolated intestinal epithelial cells. Biochim Biophys Acta. 1971 Jan 5;225(1):123–139. doi: 10.1016/0005-2736(71)90291-4. [DOI] [PubMed] [Google Scholar]
  23. Ring K. Die induktion des aktiven Transportes neutraler Amino-säuren bei Streptomyces hydrogenans. Biochim Biophys Acta. 1969 Jul 15;183(2):375–393. doi: 10.1016/0005-2736(69)90094-7. [DOI] [PubMed] [Google Scholar]
  24. Rosenberg I. H., Coleman A. L., Rosenberg L. E. The role of sodium ion in the transport of amino acids by the intestine. Biochim Biophys Acta. 1965 May 25;102(1):161–171. doi: 10.1016/0926-6585(65)90210-4. [DOI] [PubMed] [Google Scholar]
  25. Rosenberg L. E., Albrecht I., Segal S. Lysine transport in human kidney: evidence for two systems. Science. 1967 Mar 17;155(3768):1426–1428. doi: 10.1126/science.155.3768.1426. [DOI] [PubMed] [Google Scholar]
  26. Rosenberg L. E., Crawhall J. C., Segal S. Intestinal transport of cystine and cysteine in man: evidence for separate mechanisms. J Clin Invest. 1967 Jan;46(1):30–34. doi: 10.1172/JCI105508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rosenberg L. E. Cystinuria: genetic heterogeneity and allelism. Science. 1966 Dec 9;154(3754):1341–1343. doi: 10.1126/science.154.3754.1341. [DOI] [PubMed] [Google Scholar]
  28. Schultz S. G., Fuisz R. E., Curran P. F. Amino acid and sugar transport in rabbit ileum. J Gen Physiol. 1966 May;49(5):849–866. doi: 10.1085/jgp.49.5.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. THIER S. O., SEGAL S., FOX M., BLAIR A., ROSENBERG L. E. CYSTINURIA: DEFECTIVE INTESTINAL TRANSPORT OF DIBASIC AMINO ACIDS AND CYSTINE. J Clin Invest. 1965 Mar;44:442–448. doi: 10.1172/JCI105157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. THIER S., FOX M., SEGAL S., ROSENBERG L. E. CYSTINURIA: IN VITRO DEMONSTRATION OF AN INTESTINAL TRANSPORT DEFECT. Science. 1964 Jan 31;143(3605):482–484. doi: 10.1126/science.143.3605.482. [DOI] [PubMed] [Google Scholar]
  31. YUNIS A. A., ARIMURA G. K., KIPNIS D. M. AMINO ACID TRANSPORT IN BLOOD CELLS. I. EFFECT OF CATIONS ON AMINO ACID TRANSPORT IN HUMAN LEUKOCYTES. J Lab Clin Med. 1963 Sep;62:465–476. [PubMed] [Google Scholar]

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