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. 1982 Jul;70(1):23–29. doi: 10.1172/JCI110598

Metabolism of heme and bilirubin in rat and human small intestinal mucosa.

F Hartmann, D M Bissell
PMCID: PMC370221  PMID: 6806320

Abstract

Formation of heme, bilirubin, and bilirubin conjugates has been examined in mucosal cells isolated from the rat upper small intestine. Intact, viable cells were prepared by enzymatic dissociation using a combined vascular and luminal perfusion and incubated with an isotopically labeled precursor, delta-amino-[2,3-3H]levulinic acid. Labeled heme and bile pigment were formed with kinetics similar to those exhibited by hepatocytes. Moreover, the newly formed bilirubin was converted rapidly to both mono- and diglucuronide conjugates. In addition, cell-free extracts of small intestinal mucosa from rats or humans exhibited a bilirubin-UDP-glucuronyl transferase activity that was qualitatively similar to that present in liver. The data suggest that the small intestinal mucosa normally contributes to bilirubin metabolism.

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Selected References

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

  1. Anand B. S., Narang A. P., Dilawari J. B., Koshy A., Datta D. V. Bilirubin glucuronyl transferase activity in the human gastric and duodenal mucosa--a preliminary report. Indian J Med Res. 1980 Jan;71:109–111. [PubMed] [Google Scholar]
  2. Bissell D. M., Guzelian P. S. Phenotypic stability of adult rat hepatocytes in primary monolayer culture. Ann N Y Acad Sci. 1980;349:85–98. doi: 10.1111/j.1749-6632.1980.tb29518.x. [DOI] [PubMed] [Google Scholar]
  3. Bissell D. M., Hammaker L. E. Cytochrome P-450 heme and the regulation of hepatic heme oxygenase activity. Arch Biochem Biophys. 1976 Sep;176(1):91–102. doi: 10.1016/0003-9861(76)90144-2. [DOI] [PubMed] [Google Scholar]
  4. Blanckaert N. Analysis of bilirubin and bilirubin mono- and di-conjugates. Determination of their relative amounts in biological samples. Biochem J. 1980 Jan 1;185(1):115–128. doi: 10.1042/bj1850115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blanckaert N., Gollan J., Schmid R. Bilirubin diglucuronide synthesis by a UDP-glucuronic acid-dependent enzyme system in rat liver microsomes. Proc Natl Acad Sci U S A. 1979 Apr;76(4):2037–2041. doi: 10.1073/pnas.76.4.2037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Correia M. A., Schmid R. Effect of cobalt on microsomal cytochrome P-450: differences between liver and intestinal mucosa. Biochem Biophys Res Commun. 1975 Aug 18;65(4):1378–1384. doi: 10.1016/s0006-291x(75)80382-2. [DOI] [PubMed] [Google Scholar]
  7. FULOP M., SANDSON J., BRAZEAU P. DIALYZABILITY, PROTEIN BINDING, AND RENAL EXCRETION OF PLASMA CONJUGATED BILIRUBIN. J Clin Invest. 1965 Apr;44:666–680. doi: 10.1172/JCI105179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Franco D., Preaux A. M., Bismuth H., Berthelot P. Extra hepatic formation of bilirubin glucuronides in the rat. Biochim Biophys Acta. 1972 Nov 24;286(1):55–61. doi: 10.1016/0304-4165(72)90087-6. [DOI] [PubMed] [Google Scholar]
  9. Grandchamp B., Bissell D. M., Licko V., Schmid R. Formation and disposition of newly synthesized heme in adult rat hepatocytes in primary culture. J Biol Chem. 1981 Nov 25;256(22):11677–11683. [PubMed] [Google Scholar]
  10. Hartmann F., Owen R., Bissell D. M. Characterization of isolated epithelial cells from rat small intestine. Am J Physiol. 1982 Feb;242(2):G147–G155. doi: 10.1152/ajpgi.1982.242.2.G147. [DOI] [PubMed] [Google Scholar]
  11. Hoensch H., Woo C. H., Raffin S. B., Schmid R. Oxidative metabolism of foreign compounds in rat small intestine: cellular localization and dependence on dietary iron. Gastroenterology. 1976 Jun;70(6):1063–1070. [PubMed] [Google Scholar]
  12. LABBE R. F., NISHIDA G. A new method of hemin isolation. Biochim Biophys Acta. 1957 Nov;26(2):437–437. doi: 10.1016/0006-3002(57)90033-1. [DOI] [PubMed] [Google Scholar]
  13. LESTER R., HAMMAKER L., SCHMID R. A new therapeutic approach to unconjugated hyperbilirubinaemia. Lancet. 1962 Dec 15;2(7268):1257–1257. doi: 10.1016/s0140-6736(62)92820-9. [DOI] [PubMed] [Google Scholar]
  14. LESTER R., SCHMID R. Intestinal absorption of bile pigments. I. The enterohepatic circulation of bilirubin in the rat. J Clin Invest. 1963 May;42:736–746. doi: 10.1172/JCI104766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mahon W. A., Inaba T., Stone R. M. Metabolism of flurazepam by the small intestine. Clin Pharmacol Ther. 1977 Aug;22(2):228–233. doi: 10.1002/cpt1977222228. [DOI] [PubMed] [Google Scholar]
  16. OSTROW J. D., HAMMAKER L., SCHMID R. The preparation of crystalline bilirubin-C14. J Clin Invest. 1961 Aug;40:1442–1452. doi: 10.1172/JCI104375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pantuck E. J., Hsiao K. C., Kuntzman R., Conney A. H. Intestinal metabolism of phenacetin in the rat: effect of charcoal-broiled beef and rat chow. Science. 1975 Feb 28;187(4178):744–746. doi: 10.1126/science.1114320. [DOI] [PubMed] [Google Scholar]
  18. Raffin S. B., Woo C. H., Roost K. T., Price D. C., Schmid R. Intestinal absorption of hemoglobin iron-heme cleavage by mucosal heme oxygenase. J Clin Invest. 1974 Dec;54(6):1344–1352. doi: 10.1172/JCI107881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. SCHMID R., HAMMAKER L. METABOLISM AND DISPOSITION OF C14-BILIRUBIN IN CONGENITAL NONHEMOLYTIC JAUNDICE. J Clin Invest. 1963 Nov;42:1720–1734. doi: 10.1172/JCI104858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Scharf R., Ullrich V. In vitro induction of drug monooxygenase activity by phenobarbital in the isolated mouse jejunum. Naunyn Schmiedebergs Arch Pharmacol. 1973;278(3):329–332. doi: 10.1007/BF00500295. [DOI] [PubMed] [Google Scholar]
  21. Singh J., Schwarz L. R., Wiebel F. J. A rapid enzymic procedure for the determination of picomole amounts of UDP-glucuronic acid. Biochem J. 1980 Aug 1;189(2):369–372. doi: 10.1042/bj1890369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. TURNBULL A., CLETON F., FINCH C. A. Iron absorption. IV. The absorption of hemoglobin iron. J Clin Invest. 1962 Oct;41:1897–1907. doi: 10.1172/JCI104646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takesue Y., Sato R. Enzyme distribution in subcellular fractions of intestinal mucosal cells. J Biochem. 1968 Dec;64(6):873–883. doi: 10.1093/oxfordjournals.jbchem.a128969. [DOI] [PubMed] [Google Scholar]
  24. Wattenberg L. W. Effects of dietary constituents on the metabolism of chemical carcinogens. Cancer Res. 1975 Nov;35(11 Pt 2):3326–3331. [PubMed] [Google Scholar]
  25. Wong K. P. Measurement of nanogram quantities of UDP-glucuronic acid in tissues. Anal Biochem. 1977 Oct;82(2):559–563. doi: 10.1016/0003-2697(77)90194-4. [DOI] [PubMed] [Google Scholar]
  26. Zampaglione N. G., Mannering G. J. Properties of benzpyrene hydroxylase in the liver, intestinal mucosa and adrenal of untreated and 3-methylcholanthrene-treated rats. J Pharmacol Exp Ther. 1973 Jun;185(3):676–685. [PubMed] [Google Scholar]

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