Plasma Disappearance of Conjugated and Unconjugated C14 Bilirubin in the Rat with Obstructive Jaundice

Ali, Meer; Billing, Barbara H.

doi:10.3181/00379727-124-31737

Cited by 10 publications

(2 citation statements)

References 1 publication

(1 reference statement)

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“…The ratio of the specific activities obtained using method i to those using method ii averaged 0.96+0.03 (mean +SEM). These ratios compare favorably with other comparable data in the literature (16)(17)(18).…”

Section: Validity Of Methodssupporting

confidence: 80%

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

Jones¹,

Shrager²,

Bloomer³

et al. 1972

J. Clin. Invest.

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Section: Validity Of Methodssupporting

confidence: 80%

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

Jones¹,

Shrager²,

Bloomer³

et al. 1972

J. Clin. Invest.

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“…This can be inferred from the fact that bilirubin is virtually undetectable in normal rat plasma (47), even though the bilirubin production rate (mg/kg per day), estimated from the total (49), is approximately the same as in man. Furthermore, intravenously injected unconjugated radiobilirubin is cleared from the plasma of the rat with an initial Ti of only 1-2 min (50,51), and 80-95% of the injected dose is recoverable in the bile at the end of 1 hr (50,52). In man, the initial plasma Ti for intravenously injected bilirubin-14C averaged 18 min in the current studies, and recovery of isotopic bilirubin in the bile was correspondingly slow (Fig.…”

mentioning

confidence: 89%

Studies of bilirubin kinetics in normal adults

Berk¹,

Howe²,

Bloomer³

et al. 1969

J. Clin. Invest.

222

132

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A B S T R A C T This report describes studies of bilirubin kinetics in 13 healthy young adults. The plasma content of unconjugated bilirubin-14C was determined at frequent intervals for 24-30 hr after the intravenous injection of a tracer dose of unconjugated isotopic bilirubin. Fecal and urinary radioactivity were measured for 7 days. During this time cumulative recovery averaged 96% of the injected dose. The plasma curves were processed by digital computer. For the 30 hr experimental period, a sum of three exponentials, with average half-times of 18, 81, and 578 min, was required to describe the data. Using the plasma curve integral method, the hepatic bilirubin clearance (47 +10 ml/min, mean +SD), the bilirubin production rate (3.8 ±0.6 mg/kg per day), and the mean red blood cell life span (101 ±13 days) were calculated directly from the parameters of this function. To gain further insight into the metabolism of unconjugated bilirubin, the data were also used to determine the parameters of a multicompartmental model. In the model proposed, plasma unconjugated bilirubin exchanges with two additional pools, one of which is thought to represent extrahepatic extravascular, and the other intrahepatic unconjugated bilirubin. Bilirubin is eliminated from the system via the proposed intrahepatic pool. From the data and the model, pool sizes and exchange rates between compartments were calculated, and the liver: plasma concentration gradient estimated. These studies provide a detailed analysis of the kinetics of unconjugated bilirubin in a healthy normal population and are intended to serve as a reference point for studies of abnormal states.

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New concepts in bilirubin chemistry, transport and metabolism: Report of the second international bilirubin workshop, April 9–11, 1992, trieste, Italy

Tiribelli

Ostrow

1993

Hepatology

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This article is a summary of the presentations and discussions at the multidisciplinary International Bilirubin Workshop held in Trieste, Italy, in April 1992. Areas discussed included the following: (a) chemistry and physical chemistry; (b) conjugation and its genetic defects; ( c ) hepatocytic transport and its regulation; (d) the alternate pathways of bilirubin metabolism when conjugation is defective; and (e) the mechanisms of bilirubin toxicity and treatment of neonatal jaundice.Chemical Structure and Function. The fully protonated diacid form of unconjugated bilirubin (UCB) is held in a relatively rigid, ridge-tile conformation by a trio of internal hydrogen bonds between each of the two -COOH groups and the opposite dipyrromethenone half of the molecule. This internal bonding accounts for the very low water solubility and high pK'a values (both greater than 8.0) of UCB diacid. Ionization of the -COOH groups loosens these internal bonds so that the monoanion and dianion of UCB are progressively more water soluble than the diacid and interact more avidly with bile salts and albumin. At physiological pH values the major unbound species of UCB in plasma and bile is the diacid, and the major unbound anion is the monoanion (HB-). UCB diacid binds best to phospholipid membranes, whereas the monoanion appears to be the species preferentially transported across membranes, with cotransport of a proton. Bile is mildly supersaturated with UCB diacid and the dianion salt CaB but massively supersaturated with the monoanion salt Ca(HB),, which thus most readily precipitates in pigment gallstones. Peroxidation and polymerization of calcium bilirubinates, catalyzed by divalent metal cations (e.g., Cu2+), is the likely mechanism for formation of the black pigment network polymer in pigment gallstones.Biliary excretion of bile pigments requires the presence of an ionized -COO-group that is not internally bonded. Microsomal conjugation of bile pigments, by contrast, requires an internally bonded -COOH group. This explains why UCB-IXa diacid is not itself secreted into bile but is readily converted to monoglucuronide and diglucuronide conjugates (CB) that can be secreted. Hepatic uptake, or intracellular trafficking of bilirubins, is apparently regulated by differences in the affinity of binding to, and rates of dissociation from, plasma albumin and various cellular membranes and proteins, as well as rates of diffusion across the unstirred water layer. UCB, CB and heme exhibit potent physiological antioxidant properties.Coly'ugution and Its Genetic Defects. The supergene and messenger RNAs (mRNAs) for the UDP-glucuronosyltransferases (UGTs), family 1, which conjugate phenols and UCB, have been characterized in human and rat liver tissue. Each UGT shares a common C-terminal half, encoded by four constant exons at the 3' end of the gene. Mutations in these exons cause deficiencies of all UGTl isozymes. The variable upstream portion of the gene contains six unique exons, each with its own promoter; each exon encodes the N-termina...

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Plasma Disappearance of Conjugated and Unconjugated C14 Bilirubin in the Rat with Obstructive Jaundice

Cited by 10 publications

References 1 publication

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

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

Studies of bilirubin kinetics in normal adults

New concepts in bilirubin chemistry, transport and metabolism: Report of the second international bilirubin workshop, April 9–11, 1992, trieste, Italy

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