Bilirubin Metabolism in the Fœtus

Schmid, Rudi; Buckingham, Sue; Mendilla, Gloria A.; Hammaker, Lydia

doi:10.1038/1831823a0

Cited by 39 publications

(20 citation statements)

References 5 publications

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“…Therefore, homogenates were used in this study to eliminate any errcr resulting from a failure of bilirubin to penetrate intact cell wall. Activity of BGT is related to the concentration of unconjugated bilirubin, according to SCHMID et al [19]. These authors were unsuccessful in an attempt to stimulate glucuronidation of o-aminophenol by intraperitoneal loading with sodium antralinate.…”

Section: Discussionmentioning

confidence: 99%

Effects of Unconjugated Bilirubin on Bilirubin-UDP-Glucuronyl Transferase Activity in Liver of Newborn Rats

Bakken

1969

Pediatr Res

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ExtractThe bilirubin-UDP-glucuronyl transferase (BGT) activity in liver of newborn rats was measured to determine if unconjugated bilirubin could be the trigger substance of glucuronyl transferase activity. Comparison was made among norma! rats, newborn rats, and rats of mothers that had been given varying doses of unconjugated bilirubin during pregnancy.Three groups of pregnant Wistar rats were used for the experiments. Group I received bilirubin by intravenous injection once a day during the last five days of pregnancy. Group I1 received a suspension of bilirubin by intraperitoneal injection during the sixteenth to twenty-first day of pregnancy. Group I11 served as controls.Activity was determined by a modification of the method of LATHE and WALKER 114.1. Total bilirubin was determined in the incubates according to the method of FOG and BAKKEN [9], while conjugated and unconjugated bilirubin were determined by methods described by FOG and BAKKEN [lo].BGT activity was measured as bilirubin conjugated per gram wet weight liver per hour (table I). Normal newborn rats were unable to conjugate bilirubin at birth, while newborn rats of mothers that had been injected with 150 mg bilirubin for more than 24 hours showed BGT activity a t birth. Newborn rats of mothers that had received 150 mg bilirubin less than 24 hours before delivery showed no BGT activity in liver at birth, but the enzyme was activated earlier after birth in these rats than it was in normal rats.The results show that unconjugated bilirubin triggers UDP-glucuronyl transferase and thus functions as an activator for excretion of bilirubin. SpeculationThe finding that unconjugated bilirubin functions as a trigger for bilirubin-UDP-glucuronyl transferase activity does not explain the molecular mechanism that leads to increased enzyme activity. Further studies are needed to show whether the increased level of activity after birth is due to a new production of ribonucleic acid (RNA), to activation of a protein already present, or to inactivation or withdrawal of an inhibitor. The possible relation between the level of bilirubin in the serum and the conjugating capacity in the newborn should also be studied.

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Section: Discussionmentioning

confidence: 99%

Effects of Unconjugated Bilirubin on Bilirubin-UDP-Glucuronyl Transferase Activity in Liver of Newborn Rats

Bakken

1969

Pediatr Res

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“…After injection of '4C-labeled bilirubin-Illa or -XIIIa in four Wistar rats, 75-88% of the label of the addministered Illa isomer and 75% of that of the XIIIa isomer appeared in bile collected over the subsequent 3 h. Approximately half (52% for the Illa isomer and 49-59% for the XIIIa isomer) of the label was excreted as BDG. In two Gunn rats, only 4 and 5%, respectively, of injected Illa or XIIIa isomer was recovered in bile in 3 h and bilirubin glucuronides could not be detected. These results are similar to those obtained with bilirubin (29), and show that Gunn rats are unable to conjugate bilirubin-IIIa and -XIIIa.…”

Section: Experimental Series Imentioning

confidence: 99%

“…INTRODUCTION Bilirubin,' the principal degradation product of heme in mammals (1), is excreted in bile largely in the form of polar derivatives in which one or both propionic acid ,8-substituents of the pigment are esterified with a sugar, predominantly glucuronic acid (2,3). This conjugation is thought to disrupt the multiple intramolecular hydrogen bonds responsible for the nonpolar character of bilirubin and thereby renders the pigment excretable in bile (4). It is well established that formation of bilirubin monoglucuronide (BMG) is catalyzed by microsomal uridine diphosphate (UDP)-glucuronosyltransferase [UDP-glucuronate /3-glucuronosyltransferase (acceptor unspecific), EC 2.4.1.17], with UDP-glucuronic acid (UDPGlcUA) serving as sugar donor (5).…”

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confidence: 99%

Mechanism of Bilirubin Diglucuronide Formation in Intact Rats

Blanckaert¹,

Gollan²,

Schmid³

1980

J. Clin. Invest.

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A B S T R A C T Although it is well established that bilirubin monoglucuronide is formed in the liver from bilirubin by a microsomal bilirubin uridine diphosphate (UDP)-glucuronosyltransferase, the subcellular site of conversion of monoglucuronide to diglucuronide and the molecular mechanism involved in diglucuronide synthesis have not been identified. Based on in vitro studies, it has been proposed that two fundamentally different enzyme systems may be involved in diglucuronide synthesis in rat liver: (a) a microsomal UDP-glucuronosyltransferase system requiring UDPglucuronic acid as sugar donor or (b) a transglucuronidation mechanism that involves transfer ofa glucuronosyl residue from one monoglucuronide molecule to another, catalyzed by a liver plasma membrane enzyme. To clarify the mechanism by which bilirubin monoglucuronide is converted in vivo to diglucuronide, three different experimental approaches were used. First, normal rats were injected with either equal amounts of bilirubin-

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“…In 1958 we suggested that transient familial neonatal hyperbilirubinemia may result from increased amounts of a substance in the serum of certain * Submitted for publication January 26,1965; accepted May 12, 1965. This study was supported in part by research grants from the National Institutes of Health (AM-02019, pregnant women that inhibits the hepatic conjugation of bilirubin (9,10). Studies of serum inhibitor factor activity were, therefore, performed during subsequent pregnancies in some of these patients.…”

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confidence: 99%