The enzymatic formation of bilirubin glucuronide

Schmid, Rudi; Hammaker, Lydia; Axelrod, Julius

doi:10.1016/0003-9861(57)90103-0

Cited by 114 publications

(21 citation statements)

References 14 publications

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“…These have shown that glucuronic acid is transferred to bilirubin from uridine diphosphate glucuronic acid in a reaction catalyzed by the enzyme, glucuronyl transferase, which is present in the microsomes of the liver (24,28,29 (32). The bile, however, was colorless and contained only traces of unconjugated bilirubin.…”

Section: The Gunn Ratmentioning

confidence: 99%

Bile Pigments of Jaundice*

Hoffman¹,

Whitcomb²,

Butt³

et al. 1960

J. Clin. Invest.

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Current concepts concerning the formation and metabolism of bile pigments hold that bilirubin is formed from the catabolism of hemoglobin by the reticuloendothelial system, mainly in bone marrow and spleen, and that the bilirubin is then transported to the liver where it is modified and excreted. via the biliary system. These concepts are based largely on the studies by Mann, Magath and Bollman (1, 2) of the effect of total hepatectomy on mammals which show that after complete extirpation of the liver, indirect-reacting bile pigment was formed and accumulated in the serum progressively during the survival period of the animal. Bollman and Mann (3) noted that as the amount of bilirubin in the blood increased after hepatectomy, the van den Bergh reaction changed from an indirect to a direct reaction and bilirubin began to appear in the urine.Since the original work of van den Bergh, Snapper and Muller (4, 5) on the application of the Ehrlich diazo reaction to the quantitative measurement of the serum bilirubin and their observation of the differing character of the reaction in various types of jaundice, many investigators have sought to determine the fundamental basis for these differences. Despite a voluminous literature on the subject which has accumulated for more than 40 years, disagreement and lack of exact knowledge are still evident. In this paper we can cite only recent surveys encompassing the many concepts which have been proposed (6-9).

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Section: The Gunn Ratmentioning

confidence: 99%

Bile Pigments of Jaundice*

Hoffman¹,

Whitcomb²,

Butt³

et al. 1960

J. Clin. Invest.

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“…Free, water-insoluble, indirect-reacting bilirubin is conjugated prior to excretion, predominantly as an ester monoglucuronide and a diglucuronide, forming the water-soluble, direct-reacting pigments I and II, respectively (1)(2)(3)(4)(5)(6). The conjugation of bilirubin with glucuronic acid, in the presence of uridine diphosphate glucuronic acid which serves as a glucuronyl donor, is brought about by the enzyme, glucuronyl transferase.…”

mentioning

confidence: 99%

Sulfate and Glucuronide Conjugates of Bilirubin in Experimental Liver Injury*

Schoenfield¹,

Bollman²,

Hoffman³

1962

J. Clin. Invest.

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Free, water-insoluble, indirect-reacting bilirubin is conjugated prior to excretion, predominantly as an ester monoglucuronide and a diglucuronide, forming the water-soluble, direct-reacting pigments I and II, respectively (1-6). The conjugation of bilirubin with glucuronic acid, in the presence of uridine diphosphate glucuronic acid which serves as a glucuronyl donor, is brought about by the enzyme, glucuronyl transferase. It has been shown that conjugated bilirubin also contains nonglucuronide conjugates (7-13).Isselbacher and McCarthy (12), using S35-labeled sulfate, identified bilirubin sulfate chromatographically and radioautographically in the bile of rats, cats, and humans and in the serum and urine of rats with ligated bile ducts. They observed that the enzymatic biosynthesis of bilirubin sulfate in vitro involves active sulfate and requires adenosine triphosphate. These same authors speculated that the proportions of glucuronide and sulfate conjugates might be altered in certain disease states.The present study was designed to investigate the relative proportions of glucuronide and sulfate conjugates of bilirubin of laboratory animals after hepatic injury. We also examined the relative proportions of pigments I and II under these same conditions (14). MATERIALS AND METHODSExperimental conditions. Male Wistar rats, weighing 250 to 300 g, were used. Each experimental group contained 6 animals except those groups used for study of bile from the isolated liver, each of which contained 4 animals. To accomplish acute injury, animals were exposed in a closed chamber to vapors of carbon tetrachloride of constant concentration (25 mg CC1, per 50 L air) for 7 hours. Bile fistulas were prepared by cannulating the common bile ducts with polyethylene catheters. The common bile duct was ligated securely with two ties of * Abridgment of thesis submitted by Dr. Schoenfield to the Faculty of the Graduate School of the University of Minnesota in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medicine.4-0 braided silk and the duct was cut between the ties for studies of short (acute) obstruction (24 hours) and of prolonged obstruction (6 to 10 days). In one group acute obstruction was accomplished after exposure to CCl4. This was done to study the added effect of carbon tetrachloride injury on the plasma pigments inasmuch as the exposure alone did not produce jaundiced plasma. Rat liver perfusion preparations (15) were utilized in the study of pigments in bile produced by the isolated liver in response to acute CC14 injury.After bile fistulas were prepared in the control groups and in the other groups in which CC14 was given later, 100 tec inorganic radioactive sulfate (S3O,) in normal saline solution was injected intraperitoneally or into the isolated liver system. Bile was then collected for 5 hours on ice and in the dark. For study of the plasma pigments the radioactive-labeled sulfate was administered immediately after obstruction in the acute experiments and 24 hours prior to the ti...

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“…The conjugation of bilirubin is believed to occur mainly in the liver (4,5). In vitro, formation of bilirubin glucuronide has been demonstrated with a system containing liver microsomes as the enzyme source and uridine diphosphate glucuronic acid as the glucuronic acid donor (5,6). Since conjugation of bilirubin appears to be essential for its excretion in the bile, a defect in the glucuronide forming mechanism would result in impaired pigment excretion and, hence, in retention of free bilirubin in the blood.…”

mentioning

confidence: 99%