Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Aug;58(2):298–305. doi: 10.1172/JCI108472

Jejunal Perfusion of Simple and Conjugated Folates in Tropical Sprue

José J Corcino 1,2, Ann M Reisenauer 1,2, Charles H Halsted 1,2
PMCID: PMC333183  PMID: 16695965

Abstract

Absorption of labeled simple 3′,5′,9′-3H pteroylmonoglutamate, ([3H]PG-1) and conjugated pteroyl-μ[14C]glutamyl-γ-hexaglutamate, ([14C]PG-7) folates was assessed in six patients with tropical sprue, before and after 6 mo of treatment, utilizing jejunal perfusion and urinary recovery techniques. Degradation products of [14C]PG-7 which were produced during perfusion were identified by DEAE-cellulose column chromatography. Jejunal mucosal activities of folate conjugase, lactase, sucrase, and maltase were measured in every patient. Malabsorption of both [3H]PG-1 and [14C]PG-7 was found in every untreated patient, with significant improvement after therapy. The urinary excretion of 3H and 14C paralleled the luminal disappearance of both isotopes. The chromatographic patterns of intraluminal degradation products of [14C]PG-7 obtained during perfusion did not differ from those previously found in normal subjects and were similar in studies performed before and after treatment. The activity of folate conjugase was increased in the mucosa of the untreated patients when compared to the post-treatment levels while the activities of mucosal lactase, sucrase, and maltase were originally low and increased significantly after therapy. These observations suggest that folate conjugase originates at a different mucosal locus than the brush border disaccharidases, and are consistent with previous evidence that folate conjugase is an intracellular enzyme. The present studies have demonstrated unequivocal malabsorption of both simple and conjugated folates in tropical sprue. In tropical sprue, folate malabsorption is the reflection of impaired folate transport and not of impaired hydrolysis.

Full text

PDF
298

Selected References

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

  1. BUTTERWORTH C. E., Jr, SANTINI R., Jr, FROMMEYER W. B., Jr THE PTEROYLGLUTAMATE COMPONENTS OF AMERICAN DIETS AS DETERMINED BY CHROMATOGRAPHIC FRACTIONATION. J Clin Invest. 1963 Dec;42:1929–1939. doi: 10.1172/JCI104879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baugh C. M., Krumdieck C. L., Baker H. J., Butterworth C. E., Jr Studies on the absorption and metabolism of folic acid. I. Folate absorption in the dog after exposure of isolated intestinal segments to synthetic pteroylpolyglutamates of various chain lengths. J Clin Invest. 1971 Oct;50(10):2009–2021. doi: 10.1172/JCI106694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Butterworth C. E., Jr, Baugh C. M., Krumdieck C. A study of folate absorption and metabolism in man utilizing carbon-14--labeled polyglutamates synthesized by the solid phase method. J Clin Invest. 1969 Jun;48(6):1131–1142. doi: 10.1172/JCI106070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cooper H., Levitan R., Fordtran J. S., Ingelfinger F. J. A method for studying absorption of water and solute from the human small intestine. Gastroenterology. 1966 Jan;50(1):1–7. [PubMed] [Google Scholar]
  5. Dahlqvist A. Assay of intestinal disaccharidases. Anal Biochem. 1968 Jan;22(1):99–107. doi: 10.1016/0003-2697(68)90263-7. [DOI] [PubMed] [Google Scholar]
  6. GROSSOWICZ N., MANDELBAUM-SHAVIT F., DAVIDOFF R., ARONOVITCH J. Microbiologic determination of folic acid derivatives in blood. Blood. 1962 Nov;20:609–616. [PubMed] [Google Scholar]
  7. Gerson C. D., Cohen N., Hepner G. W., Brown N., Herbert V., Janowitz H. D. Folic acid absorption in man: enhancing effect of glucose. Gastroenterology. 1971 Aug;61(2):224–227. [PubMed] [Google Scholar]
  8. Godwin H. A., Rosenberg I. H. Comparative studies of the intestinal absorption of [3H]pteroylmonoglutamate and [3H]pteroylheptaglutamate in man. Gastroenterology. 1975 Aug;69(2):364–373. [PubMed] [Google Scholar]
  9. Godwin H. A., Rosenberg I. H., Ferenz C. R., Jacobs P. M., Meienhofer J. The synthesis of biologically active pteroyloligo- 0L-glutamates (folic acid conjugates). Evaluation of ( 3 H)pteroylheptaglutamate for metabolic studies. J Biol Chem. 1972 Apr 25;247(8):2266–2271. [PubMed] [Google Scholar]
  10. HERBERT V., BAKER H., FRANK O., PASHER I., SOBOTKA H., WASSERMAN L. R. The measurement of folic acid activity in serum: a diagnostic aid in the differentiation of the megaloblastic anemias. Blood. 1960 Feb;15:228–235. [PubMed] [Google Scholar]
  11. Halsted C. H., Baugh C. M., Butterworth C. E., Jr Jejunal perfusion of simple and conjugated folates in man. Gastroenterology. 1975 Feb;68(2):261–269. [PubMed] [Google Scholar]
  12. Halsted C. H., Reisenauer A., Back C., Gotterer G. S. In vitro uptake and metabolism of pteroylpolyglutamate by rat small intestine. J Nutr. 1976 Apr;106(4):485–492. doi: 10.1093/jn/106.4.485. [DOI] [PubMed] [Google Scholar]
  13. Hoffbrand A. V., Necheles T. F., Maldonado N., Horta E., Santini R. Malabsorption of folate polyglutamates in tropical sprue. Br Med J. 1969 May 31;2(5656):543–547. doi: 10.1136/bmj.2.5656.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoffbrand A. V., Peters T. J. The subcellular localization of pteroyl polyglutamate hydrolase and folate in guinea pig intestinal mucosa. Biochim Biophys Acta. 1969 Dec 30;192(3):479–485. doi: 10.1016/0304-4165(69)90397-3. [DOI] [PubMed] [Google Scholar]
  15. Jägerstad M., Lindstrand K., Nordén A., Westesson A. K., Lindberg T. The folate conjugase activity of the intestinal mucosa in celiac disease. Scand J Gastroenterol. 1974;9(3):255–259. [PubMed] [Google Scholar]
  16. Klipstein F. A., Beauchamp I., Corcino J. J., Maldonado M., Tomasini J. T., Maldonado N., Rubio C., Schenk E. A. Nutritional status and intestinal function among rural populations of the West Indies. II. Barrio Nuevo, Puerto Rico. Gastroenterology. 1972 Nov;63(5):758–767. [PubMed] [Google Scholar]
  17. Krumdieck C. L., Baugh C. M. Radioactive assay of folic acid polyglutamate conjugase(s). Anal Biochem. 1970 May;35(1):123–129. doi: 10.1016/0003-2697(70)90017-5. [DOI] [PubMed] [Google Scholar]
  18. Krumdieck C. L., Baugh C. M. The solid-phase synthesis of polyglutamates of folic acid. Biochemistry. 1969 Apr;8(4):1568–1572. doi: 10.1021/bi00832a036. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Rosenberg I. H., Godwin H. A. The digestion and absorption of dietary folate. Gastroenterology. 1971 Mar;60(3):445–463. [PubMed] [Google Scholar]
  21. Rosenberg I. H., Streiff R. R., Godwin H. A., Castle W. B. Absorption of polyglutamic folate: participation of deconjugating enzymes of the intestinal mucosa. N Engl J Med. 1969 May 1;280(18):985–988. doi: 10.1056/NEJM196905012801804. [DOI] [PubMed] [Google Scholar]
  22. SPRAY G. H. An improved method for the rapid estimation of vitamin B12 in serum. Clin Sci. 1955 Nov;14(4):661–667. [PubMed] [Google Scholar]
  23. Schenk E. A., Klipstein F. A. Tropical jejunitis (tropical enteropathy). A protocol for the evaluation of small bowel biopsies. Am J Clin Nutr. 1972 Oct;25(10):1108–1117. doi: 10.1093/ajcn/25.10.1108. [DOI] [PubMed] [Google Scholar]

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

RESOURCES