Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1971 Nov;50(11):2259–2265. doi: 10.1172/JCI106723

The measurement of the synthetic rate of bilirubin from hepatic hemes in patients with acute intermittent porphyria

E A Jones 1, J R Bloomer 1, N I Berlin 1
PMCID: PMC292167  PMID: 5096511

Abstract

A new method for the direct measurement in vivo of the synthetic rate of bilirubin from hepatic hemes is proposed. This method depends on the application of the labeled precursor-product relationship to the hepatic pool of porphobilinogen, which is a common precursor of both urinary porphobilinogen and hepatic-synthesized bilirubin. The hepatic pool of porphobilinogen is labeled by means of an intravenous injection of δ-aminolevulinic acid-4-14C. The proportion of total bilirubin production which is derived from hepatic hemes is calculated from the ratio of the mean 14C specific activities of stercobilin and porphobilinogen estimated in pooled specimens of feces and urine, respectively. The method can be most readily applied to patients with acute intermittent porphyria, as the appreciable quantities of prophobilinogen in the urine of these patients greatly facilitate the measurement of porphobilinogen-14C specific activity. In three patients with acute intermittent porphyria, values obtained for the synthetic rate of bilirubin from hepatic hemes were 20.7, 15.8, and 13.3% of total bilirubin production.

Full text

PDF
2259

Selected References

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

  1. BERLIN N. I., NEUBERGER A., SCOTT J. J. The metabolism of delta -aminolaevulic acid. 1. Normal pathways, studied with the aid of 15N. Biochem J. 1956 Sep;64(1):80–90. doi: 10.1042/bj0640080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barrett V., Berk P. D., Menken M., Berlin N. I. Bilirubin turnover studies in normal and pathologic states using bilirubin-14C. Ann Intern Med. 1968 Feb;68(2):355–377. doi: 10.7326/0003-4819-68-2-355. [DOI] [PubMed] [Google Scholar]
  3. Berk P. D., Howe R. B., Bloomer J. R., Berlin N. I. Studies of bilirubin kinetics in normal adults. J Clin Invest. 1969 Nov;48(11):2176–2190. doi: 10.1172/JCI106184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bloomer J. R., Berk P. D., Bonkowsky H. L., Stein J. A., Berlin N. I., Tschudy D. P. Blood volume and bilirubin production in acute intermittent porphyria. N Engl J Med. 1971 Jan 7;284(1):17–20. doi: 10.1056/NEJM197101072840104. [DOI] [PubMed] [Google Scholar]
  5. COOKSON G. H., RIMINGTON C. Porphobilinogen. Biochem J. 1954 Jul;57(3):476–484. doi: 10.1042/bj0570476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. GRAY C. H., NEUBERGER A., SNEATH P. H. A. Studies in congenital porphyria. 2. Incorporation of 15N in the stercobilin in the normal and in the porphyric. Biochem J. 1950 Jun-Jul;47(1):87–92. doi: 10.1042/bj0470087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Howe R. B., Berk P. D., Bloomer J. R., Berlin N. I. Preparation and properties of specifically labeled radiochemically stable 3H-bilirubin. J Lab Clin Med. 1970 Mar;75(3):499–502. [PubMed] [Google Scholar]
  8. ISRAELS L. G., YAMAMOTO T., SKANDERBEG J., ZIPURSKY A. Shunt bilirubin: evidence for two components. Science. 1963 Mar 15;139(3559):1054–1055. doi: 10.1126/science.139.3559.1054. [DOI] [PubMed] [Google Scholar]
  9. LONDON I. M., WEST R., SHEMIN D., RITTENBERG D. On the origin of bile pigment in normal man. J Biol Chem. 1950 May;184(1):351–358. [PubMed] [Google Scholar]
  10. Landaw S. A., Callahan E. W., Jr, Schmid R. Catabolism of heme in vivo: comparison of the simultaneous production of bilirubin and carbon monoxide. J Clin Invest. 1970 May;49(5):914–925. doi: 10.1172/JCI106311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Levitt M., Schacter B. A., Zipursky A., Israels L. G. The nonerythropoietic component of early bilirubin. J Clin Invest. 1968 Jun;47(6):1281–1294. doi: 10.1172/JCI105820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. MAUZERALL D., GRANICK S. The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. J Biol Chem. 1956 Mar;219(1):435–446. [PubMed] [Google Scholar]
  13. NEUBERGER A., SCOTT J. J. Aminolaevulinic acid and porphyrin biosynthesis. Nature. 1953 Dec 12;172(4389):1093–1094. doi: 10.1038/1721093a0. [DOI] [PubMed] [Google Scholar]
  14. REEVE E. B., PEARSON J. R., MARTZ D. C. Plasma protein synthesis in the liver: method for measurement of albumin formation in vivo. Science. 1963 Mar 8;139(3558):914–916. doi: 10.1126/science.139.3558.914. [DOI] [PubMed] [Google Scholar]
  15. Robinson S. H., Lester R., Crigler J. F., Jr, Tsong M. Early-labeled peak of bile pigment in man. Studies with glycine-14C and delta-aminolevulinic acid-3H. N Engl J Med. 1967 Dec 21;277(25):1323–1329. doi: 10.1056/NEJM196712212772501. [DOI] [PubMed] [Google Scholar]
  16. Robinson S. H., Owen C. A., Jr, Flock E. V., Schmid R. Bilirubin formation in the liver from nonhemoglobin sources. Experiments with isolated, perfused rat liver. Blood. 1965 Dec;26(6):823–829. [PubMed] [Google Scholar]
  17. Robinson S. H., Tsong M., Brown B. W., Schmid R. The sources of bile pigment in the rat: studies of the "early labeled" fraction. J Clin Invest. 1966 Oct;45(10):1569–1586. doi: 10.1172/JCI105463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. WATSON C. J., LOWRY P. T., SBOROV V. E., HOLLINSHEAD W. H., KOHAN S., MATTE H. O. A simple method of isolation of crystalline stercobilin or urobilin from feces. J Biol Chem. 1953 Feb;200(2):697–701. [PubMed] [Google Scholar]
  19. WEBER A. P., SCHALM L. Quantitative separation and determination of bilirubin and conjugated bilirubin in human serum. Clin Chim Acta. 1962 Nov;7:805–810. doi: 10.1016/0009-8981(62)90063-3. [DOI] [PubMed] [Google Scholar]
  20. YAMAMOTO T., SKANDERBEG J., ZIPURSKY A., ISRAELS L. G. THE EARLY APPEARING BILIRUBIN: EVIDENCE FOR TWO COMPONENTS. J Clin Invest. 1965 Jan;44:31–41. doi: 10.1172/JCI105124. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES