The Measurement of the Synthetic Rate of Bilirubin from Hepatic Hemes in Patients with Acute Intermittent Porphyria

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1971 Nov 1

PMID 5096511

Citations 4

Authors

E A Jones

J R Bloomer

N I BERLIN

Affiliations

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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 delta-aminolevulinic acid-4-(14)C. The proportion of total bilirubin production which is derived from hepatic hemes is calculated from the ratio of the mean (14)C 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-(14)C 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.

Citing Articles

Degradation of endogenous hepatic heme by pathways not yielding carbon monoxide. Studies in normal rat liver and in primary hepatocyte culture.

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Quantitative studies of the delivery of hepatic-synthesized bilirubin to plasma utilizing -aminolevulinic acid-4- 14 C and bilirubin- 3 H in man.

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The porphyrias: a review.

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Role of ineffective erythropoiesis in anaemia of RA.

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References

REEVE E, PEARSON J, MARTZ D . Plasma protein synthesis in the liver: method for measurement of albumin formation in vivo. Science. 1963; 139(3558):914-6. DOI: 10.1126/science.139.3558.914. View

Watson C, LOWRY P, SBOROV V, HOLLINSHEAD W, Kohan S, MATTE H . A simple method of isolation of crystalline stercobilin or urobilin from feces. J Biol Chem. 1953; 200(2):697-701. View

Yamamoto T, SKANDERBEG J, Zipursky A, ISRAELS L . THE EARLY APPEARING BILIRUBIN: EVIDENCE FOR TWO COMPONENTS. J Clin Invest. 1965; 44:31-41. PMC: 442016. DOI: 10.1172/JCI105124. View

LONDON I, West R, SHEMIN D, Rittenberg D . On the origin of bile pigment in normal man. J Biol Chem. 1950; 184(1):351-8. View

GRAY C, Neuberger A, SNEATH P . Studies in congenital porphyria. 2. Incorporation of 15N in the stercobilin in the normal and in the porphyric. Biochem J. 1950; 47(1):87-92. PMC: 1275165. DOI: 10.1042/bj0470087. View

ROBINSON S, Tsong M, BROWN B, Schmid R . The sources of bile pigment in the rat: studies of the "early labeled" fraction. J Clin Invest. 1966; 45(10):1569-86. PMC: 292838. DOI: 10.1172/JCI105463. View

COOKSON G, Rimington C . Porphobilinogen. Biochem J. 1954; 57(3):476-84. PMC: 1269786. DOI: 10.1042/bj0570476. View

LANDAW S, Callahan Jr E, Schmid R . Catabolism of heme in vivo: comparison of the simultaneous production of bilirubin and carbon monoxide. J Clin Invest. 1970; 49(5):914-25. PMC: 535764. DOI: 10.1172/JCI106311. View

ROBINSON S, Lester R, CRIGLER Jr J, Tsong M . Early-labeled peak of bile pigment in man. Studies with glycine-14C and delta-aminolevulinic acid-3H. N Engl J Med. 1967; 277(25):1323-9. DOI: 10.1056/NEJM196712212772501. View

10.

Barrett V, Berk P, Menken M, BERLIN N . Bilirubin turnover studies in normal and pathologic states using bilirubin-14C. Ann Intern Med. 1968; 68(2):355-77. DOI: 10.7326/0003-4819-68-2-355. View

11.

Neuberger A, Scott J . Aminolaevulinic acid and porphyrin biosynthesis. Nature. 1953; 172(4389):1093-4. DOI: 10.1038/1721093a0. View

12.

Levitt M, Schacter B, Zipursky A, ISRAELS L . The nonerythropoietic component of early bilirubin. J Clin Invest. 1968; 47(6):1281-94. PMC: 297284. DOI: 10.1172/JCI105820. View

13.

Bloomer J, Berk P, Bonkowsky H, Stein J, BERLIN N, TSCHUDY D . Blood volume and bilirubin production in acute intermittent porphyria. N Engl J Med. 1971; 284(1):17-20. DOI: 10.1056/NEJM197101072840104. View

14.

Berk P, HOWE R, Bloomer J, BERLIN N . Studies of bilirubin kinetics in normal adults. J Clin Invest. 1969; 48(11):2176-90. PMC: 297471. DOI: 10.1172/JCI106184. View

15.

Mauzerall D, Granick S . The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. J Biol Chem. 1956; 219(1):435-46. View

16.

BERLIN N, Neuberger A, Scott J . The metabolism of delta -aminolaevulic acid. 1. Normal pathways, studied with the aid of 15N. Biochem J. 1956; 64(1):80-90. PMC: 1199693. DOI: 10.1042/bj0640080. View

17.

Weber A, SCHALM L . Quantitative separation and determination of bilirubin and conjugated bilirubin in human serum. Clin Chim Acta. 1962; 7:805-10. DOI: 10.1016/0009-8981(62)90063-3. View

18.

ROBINSON S, OWEN Jr C, FLOCK E, Schmid R . Bilirubin formation in the liver from nonhemoglobin sources. Experiments with isolated, perfused rat liver. Blood. 1965; 26(6):823-9. View

19.

HOWE R, Berk P, Bloomer J, BERLIN N . Preparation and properties of specifically labeled radiochemically stable 3H-bilirubin. J Lab Clin Med. 1970; 75(3):499-502. View

20.

ISRAELS L, Yamamoto T, SKANDERBEG J, Zipursky A . Shunt bilirubin: evidence for two components. Science. 1963; 139(3559):1054-5. DOI: 10.1126/science.139.3559.1054. View