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. 1974 Oct;54(4):810–818. doi: 10.1172/JCI107821

Formation and Excretion of Pyrrole-2-Carboxylate in Man

Anne M Heacock 1, Elijah Adams 1
PMCID: PMC301621  PMID: 4430715

Abstract

A detailed investigation of the purification of pyrrole-2-carboxylate (PCA) from human and rat urine indicates that previously reported mean values overestimate the correct quantity of free PCA by a factor of approximately three for rat urine and approximately five for human urine. Although several criteria of purity were satisfied by a previous method, pyrrole-reactive impurities were still present in the final fractions. These impurities are separated from PCA by chromatography through an amino acid analyzer ion-exchange resin. With the corrected method, normal human values for endogenous urinary PCA in 16 individuals averaged 0.51 μmol/day, with a range of 0.20-1.3 μmol and a SD of 0.31 μmol. The probable source of human PCA is free hydroxy-L-proline, as inferred from the high value for PCA in the urine of a subject with hereditary hydroxyprolinemia, and from the threeto eightfold elevation in PCA excretion by two normal subjects after a large oral load of hydroxyl-L-proline. Subcutaneous administration of [2-14C]PCA to a single human subject indicated almost complete conversion of the exogenous compound to derivatives, which are largely excreted in the urine. Data are discussed suggesting that much or all of the PCA in human urine may be formed in urine from a labile precursor, presumably Δ1-pyrroline-4-hydroxy-2-carboxylate.

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Selected References

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

  1. Adams E. Metabolism of proline and of hydroxyproline. Int Rev Connect Tissue Res. 1970;5:1–91. doi: 10.1016/b978-0-12-363705-5.50007-5. [DOI] [PubMed] [Google Scholar]
  2. BOUTHILLIER L. P., LETELLIER G. The formation of 2-pyrrolecarboxylic acid from hydroxy-D- and allohydroxy-D-proline. Can J Biochem Physiol. 1956 Nov;34(6):1123–1129. [PubMed] [Google Scholar]
  3. EFRON M. L., BIXBY E. M., PRYLES C. V. HYDROXYPROLINEMIA. II. A RARE METABOLIC DISEASE DUE TO A DEFICIENCY OF THE ENZYME "HYDROXYPROLINE OXIDASE". N Engl J Med. 1965 Jun 24;272:1299–1309. doi: 10.1056/NEJM196506242722501. [DOI] [PubMed] [Google Scholar]
  4. Efron M. L., Bixby E. M., Hockaday T. D., Smith L. H., Jr, Meshorer E. Hydroxyprolinemia. 3. The origin of free hydroxyproline in hydroxyprolinemia. Collagen turnover. Evidence for biosynthetic pathway in man. Biochim Biophys Acta. 1968 Sep 3;165(2):238–250. doi: 10.1016/0304-4165(68)90052-4. [DOI] [PubMed] [Google Scholar]
  5. Finlay T. H., Adams E. Kinetic and structural studies of hydroxyproline 2-epimerase. J Biol Chem. 1970 Oct 25;245(20):5248–5260. [PubMed] [Google Scholar]
  6. GERBER G. B., GERBER G., ALTMAN K. I. Some interrelated aspects of proline and hydroxyproline metabolism. Nature. 1960 Mar 12;185:767–768. doi: 10.1038/185767a0. [DOI] [PubMed] [Google Scholar]
  7. GERBER G. B., TRAELNES K. R., WOOD D., ALTMAN K. I. THE QUANTITATIVE DETERMINATION OF PYRROLE-2-CARBOXYLIC ACID IN URINE. Clin Chim Acta. 1964 Feb;9:185–187. doi: 10.1016/0009-8981(64)90015-4. [DOI] [PubMed] [Google Scholar]
  8. GOTTSCHALK A. 2-Carboxypyrrole: its preparation from and its precursor in mucoproteins. Biochem J. 1955 Oct;61(2):298–307. doi: 10.1042/bj0610298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gryder R. M., Adams E. Inducible degradation of hydroxyproline in Pseudomonas putida: pathway regulation and hydroxyproline uptake. J Bacteriol. 1969 Jan;97(1):292–306. doi: 10.1128/jb.97.1.292-306.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heacock A. M., Adams E. Hydroxy-L-proline as a substrate for hog kidney D-amino acid oxidase. Biochem Biophys Res Commun. 1974 Mar 15;57(1):279–285. doi: 10.1016/s0006-291x(74)80387-6. [DOI] [PubMed] [Google Scholar]
  11. Heacock A. M., Adams E. Source of pyrrole-2-carboxylate in mammalian urine. Biochem Biophys Res Commun. 1973 Jan 23;50(2):392–397. doi: 10.1016/0006-291x(73)90853-x. [DOI] [PubMed] [Google Scholar]
  12. Kivirikko K. I. Urinary excretion of hydroxyproline in health and disease. Int Rev Connect Tissue Res. 1970;5:93–163. doi: 10.1016/b978-0-12-363705-5.50008-7. [DOI] [PubMed] [Google Scholar]
  13. LETELLIER G., BOUTHILLIER L. P. Synthesis of 2-pyrrolecarboxylic (C14O2H) acid and study of its metabolism in the intact rat. Can J Biochem Physiol. 1957 Oct;35(10):811–817. [PubMed] [Google Scholar]
  14. NEUMAN R. E., LOGAN M. A. The determination of hydroxyproline. J Biol Chem. 1950 May;184(1):299–306. [PubMed] [Google Scholar]
  15. RADHAKRISHNAN A. N., MEISTER A. Conversion of hydroxyproline to pyrrole-2-carboxylic acid. J Biol Chem. 1957 May;226(1):559–571. [PubMed] [Google Scholar]
  16. 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]
  17. Singh R. M., Adams E. Enzymatic deamination of delta-1-pyrroline-4-hydroxy-2-carboxylate to 2,5-dioxovalerate (alpha-ketoglutaric semialdehyde). J Biol Chem. 1965 Nov;240(11):4344–4351. [PubMed] [Google Scholar]
  18. WOLF G., BERGER C. R. The metabolism of hydroxyproline in the intact rat; incorporation of hydroxyproline into protein and urinary metabolites. J Biol Chem. 1958 Jan;230(1):231–240. [PubMed] [Google Scholar]
  19. Weiss P. H., Klein L. The quantitative relationship of urinary peptide hydroxyproline excretion to collagen degradation. J Clin Invest. 1969 Jan;48(1):1–10. doi: 10.1172/JCI105957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. YONEYA T., ADAMS E. Hydroxyproline metabolism. V. Inducible allohydroxy-D-proline oxidase of Pseudomonas. J Biol Chem. 1961 Dec;236:3272–3279. [PubMed] [Google Scholar]
  21. Yamanishi Y., Iguchi M., Oyama H., Matsumura Y. Collagen metabolism. I. Significance of urinary pyrrole-2-carboxylic acid. J Clin Endocrinol Metab. 1972 Jul;35(1):55–58. doi: 10.1210/jcem-35-1-55. [DOI] [PubMed] [Google Scholar]

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