Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1968 Apr;47(4):823–835. doi: 10.1172/JCI105776

Renal tubular transport of proline, hydroxyproline, and glycine

III. Genetic basis for more than one mode of transport in human kidney

Charles R Scriver 1
PMCID: PMC297232  PMID: 5641621

Abstract

Impaired renal tubular transport of proline, hydroxyproline, and glycine was inherited as an autosomal recessive trait in two Ashkenazi-Jewish pedigrees and one French-Canadian family; the heterozygotes for the trait exhibited hyperglycinuria only. Intestinal transport of imino acids and glycine was not impaired in homozygotes. It is possible that more than one mutant allele may occur at a locus controlling tubular transport of the imino acids and glycine, since one subject with the imino-glycinuric phenotype had one parent who was not hyperglycinuric.

More than 60% of the specific tubular transport function is still available in homozygotes for absorption of imino acids and glycine at endogenous substrate concentrations; however, this persistent transport is already saturated at these concentrations in contrast to the large capacity available in normal subjects. Furthermore, the glycine portion of this persistent transport is noninhibitable by imino acids in contrast to the normal situation. The imino acids can inhibit each other's uptake in mutant and normal phenotypes. Two modes of transport for the imino acids and glycine are proposed to explain these observations: (1) a common system with high capacity, and (2) two additional systems, each with low capacity (one-tenth or less of the common system). One of these systems is apparently shared by proline and hydroxyproline. The mutant allele(s) observed in this investigation occur at the locus for the common system.

Full text

PDF

Selected References

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

  1. BOJESEN E. A method for determination of inulin in plasma and urine. Acta Med Scand Suppl. 1952;266:275–282. doi: 10.1111/j.0954-6820.1952.tb13376.x. [DOI] [PubMed] [Google Scholar]
  2. Brodehl J., Gellissen K., Kowalewski S. Isolierter Defekt der tubulären Cystin-Rückresorption in einer Familie mit idiopathischem Hypoparathyroidismus. Klin Wochenschr. 1967 Jan 1;45(1):38–40. doi: 10.1007/BF01745737. [DOI] [PubMed] [Google Scholar]
  3. CUSWORTH D. C., DENT C. E. Renal clearances of amino acids in normal adults and in patients with aminoaciduria. Biochem J. 1960 Mar;74:550–561. doi: 10.1042/bj0740550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Christensen H. N. Some transport lessons taught by the organic solute. Perspect Biol Med. 1967 Spring;10(3):471–494. doi: 10.1353/pbm.1967.0032. [DOI] [PubMed] [Google Scholar]
  5. DE VRIES A., KOCHWA S., LAZEBNIK J., FRANK M., DJALDETTI M. Glycinuria, a hereditary disorder associated with nephrolithiasis. Am J Med. 1957 Sep;23(3):408–415. doi: 10.1016/0002-9343(57)90320-0. [DOI] [PubMed] [Google Scholar]
  6. DRUMMOND K. N., MICHAEL A. F., ULSTROM R. A., GOOD R. A. THE BLUE DIAPER SYNDROME: FAMILIAL HYPERCALCEMIA WITH NEPHROCALCINOSIS AND INDICANURIA; A NEW FAMILIAL DISEASE, WITH DEFINITION OF THE METABOLIC ABNORMALITY. Am J Med. 1964 Dec;37:928–948. doi: 10.1016/0002-9343(64)90134-2. [DOI] [PubMed] [Google Scholar]
  7. Dent C. E. A study of the behaviour of some sixty amino-acids and other ninhydrin-reacting substances on phenol-;collidine' filter-paper chromatograms, with notes as to the occurrence of some of them in biological fluids. Biochem J. 1948;43(2):169–180. [PMC free article] [PubMed] [Google Scholar]
  8. Finerman G. A., Rosenberg L. E. Amino acid transport in bone. Evidence for separate transport systems for neutral amino and imino acids. J Biol Chem. 1966 Apr 10;241(7):1487–1493. [PubMed] [Google Scholar]
  9. Goodman S. I., McIntyre C. A., Jr, O'Brien D. Impaired intestinal transport of proline in a patient with familial iminoaciduria. J Pediatr. 1967 Aug;71(2):246–249. doi: 10.1016/s0022-3476(67)80081-7. [DOI] [PubMed] [Google Scholar]
  10. Grenson M. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. II. Evidence for a specific lysine-transporting system. Biochim Biophys Acta. 1966 Oct 31;127(2):339–346. doi: 10.1016/0304-4165(66)90388-6. [DOI] [PubMed] [Google Scholar]
  11. HARRIS H., MITTWOCH U., ROBSON E. B., WARREN F. L. The pattern of amino-acid excretion in cystinuria. Ann Hum Genet. 1955 Feb;19(3):196–208. doi: 10.1111/j.1469-1809.1955.tb01344.x. [DOI] [PubMed] [Google Scholar]
  12. JOSEPH R., RIBIERRE M., JOB J. C., GIRAULT M. Maladie familiale associant des convulsions à début très précoce, une hyperalbuminorachie et une hyperaminoacidurie. Arch Fr Pediatr. 1958;15(3):374–387. [PubMed] [Google Scholar]
  13. MILNE M. D., CRAWFORD M. A., GIRAO C. B., LOUGHRIDGE L. W. The metabolic disorder in Hartnup disease. Q J Med. 1960 Jul;29:407–421. [PubMed] [Google Scholar]
  14. MILNE M. D. DISORDERS OF AMINO-ACID TRANSPORT. Br Med J. 1964 Feb 8;1(5379):327–336. doi: 10.1136/bmj.1.5379.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miller M. C. Familial cirrhosis with hepatoma. Am J Dig Dis. 1967 Jun;12(6):633–638. doi: 10.1007/BF02233502. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Morikawa T., Tada K., Ando T., Yoshida T., Yokoyama Y., Arakawa T. Prolinuria: defect in intestinal absorption of imino acids and glycine. Tohoku J Exp Med. 1966 Oct;90(2):105–116. doi: 10.1620/tjem.90.105. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Rosenberg L. E., Downing S., Durant J. L., Segal S. Cystinuria: biochemical evidence for three genetically distinct diseases. J Clin Invest. 1966 Mar;45(3):365–371. doi: 10.1172/JCI105351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. SCRIVER C. R., DAVIES E., CULLEN A. M. APPLICATION OF A SIMPLE MICROMETHOD TO THE SCREENING OF PLASMA FOR A VARIETY OF AMINOACIDOPATHIES. Lancet. 1964 Aug 1;2(7353):230–232. doi: 10.1016/s0140-6736(64)90183-7. [DOI] [PubMed] [Google Scholar]
  22. SCRIVER C. R., EFRON M. L., SCHAFER I. A. RENAL TUBULAR TRANSPORT OF PROLINE, HYDROXYPROLINE, AND GLYCINE IN HEALTH AND IN FAMILIAL HYPERPROLINEMIA. J Clin Invest. 1964 Mar;43:374–385. doi: 10.1172/JCI104922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. SCRIVER C. R. HARTNUP DISEASE: A GENETIC MODIFICATION OF INTESTINAL AND RENAL TRANSPORT OF CERTAIN NEUTRAL ALPHA-AMINO ACIDS. N Engl J Med. 1965 Sep 2;273:530–532. doi: 10.1056/NEJM196509022731005. [DOI] [PubMed] [Google Scholar]
  24. SCRIVER C. R., WILSON O. H. POSSIBLE LOCATIONS FOR A COMMON GENE PRODUCT IN MEMBRANE TRANSPORT OF IMINO-ACIDS AND GLYCINE. Nature. 1964 Apr 4;202:92–93. doi: 10.1038/202092a0. [DOI] [PubMed] [Google Scholar]
  25. Scriver C. R., Davies E. Endogenous renal clearance rates of free amino acids in pre-pubertal children. (Employing an accelerated procedure for elution chromatography of basic amino acids on ion exchange resin). Pediatrics. 1965 Oct;36(4):592–598. [PubMed] [Google Scholar]
  26. Scriver C. R., Goldman H. Renal tubular transport of proline, hydroxyproline, and glycine. II. Hydroxy-l-proline as substrate and as inhibitor in vivo. J Clin Invest. 1966 Aug;45(8):1357–1363. doi: 10.1172/JCI105443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Scriver C. R. Membrane transport in disorders of imino-acid metabolism. Am J Dis Child. 1967 Jan;113(1):170–174. doi: 10.1001/archpedi.1967.02090160220038. [DOI] [PubMed] [Google Scholar]
  28. Scriver C. R., Wilson O. H. Amino acid transport: evidence for genetic control of two types in human kidney. Science. 1967 Mar 17;155(3768):1428–1430. doi: 10.1126/science.155.3768.1428. [DOI] [PubMed] [Google Scholar]
  29. Tada K., Morikawa T., Ando T., Yoshida T., Minagawa A. Prolinuria: a new renal tubular defect in transport of proline and glycine. Tohoku J Exp Med. 1965 Nov 25;87(2):133–143. doi: 10.1620/tjem.87.133. [DOI] [PubMed] [Google Scholar]
  30. Wilson O. H., Scriver C. R. Specificity of transport of neutral and basic amino acids in rat kidney. Am J Physiol. 1967 Jul;213(1):185–190. doi: 10.1152/ajplegacy.1967.213.1.185. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES