HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zucker, S. D. Articles by Hoppin, A. G. Search for Related Content PubMed PubMed Citation Articles by Zucker, S. D. Articles by Hoppin, A. G. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 16, 10852-10862, April 16, 1999

Unconjugated Bilirubin Exhibits Spontaneous Diffusion through Model Lipid Bilayers and Native Hepatocyte Membranes

Stephen D. Zucker, Wolfram Goessling^¶, and Alison G. Hoppin

From the  Division of Digestive Diseases, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0595, the ^¶ Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, and the  Division of Pediatric Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts 02114

The liver is responsible for the clearance and metabolism of unconjugated bilirubin, the hydrophobic end-product of heme catabolism. Although several putative bilirubin transporters have been described, it has been alternatively proposed that bilirubin enters the hepatocyte by passive diffusion through the plasma membrane. In order to elucidate the mechanism of bilirubin uptake, we measured the rate of bilirubin transmembrane diffusion (flip-flop) using stopped-flow fluorescence techniques. Unconjugated bilirubin rapidly diffuses through model phosphatidylcholine vesicles, with a first-order rate constant of 5.3 s¹ (t_1/2 = 130 ms). The flip-flop rate is independent of membrane cholesterol content, phospholipid acyl saturation, and lipid packing, consistent with thermodynamic analyses demonstrating minimal steric constraint to bilirubin transmembrane diffusion. The coincident decrease in pH of the entrapped vesicle volume supports a mechanism whereby the bilirubin molecule crosses the lipid bilayer as the uncharged diacid. Transport of bilirubin by native rat hepatocyte membranes exhibits kinetics comparable with that in model vesicles, suggesting that unconjugated bilirubin crosses cellular membranes by passive diffusion through the hydrophobic lipid core. In contrast, there is no demonstrable flip-flop of bilirubin diglucuronide or bilirubin ditaurate in phospholipid vesicles, yet these compounds rapidly traverse isolated rat hepatocyte membranes, confirming the presence of a facilitated uptake system(s) for hydrophilic bilirubin conjugates.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				P. Keshavan, T. L. Deem, S. J. Schwemberger, G. F. Babcock, J. M. Cook-Mills, and S. D. Zucker Unconjugated Bilirubin Inhibits VCAM-1-Mediated Transendothelial Leukocyte Migration J. Immunol., March 15, 2005; 174(6): 3709 - 3718. [Abstract] [Full Text] [PDF]

				J D Ostrow and C Tiribelli Bilirubin, a curse and a boon Gut, December 1, 2003; 52(12): 1668 - 1670. [Full Text] [PDF]

				D. Mesotten, G. Van den Berghe, C. Liddle, S. Coulter, F. McDougall, R. C. Baxter, and P. J. D. Delhanty Growth Hormone Modulation of the Rat Hepatic Bile Transporter System in Endotoxin-Induced Cholestasis Endocrinology, September 1, 2003; 144(9): 4008 - 4017. [Abstract] [Full Text] [PDF]

				P. Wang, R. B. Kim, J. R. Chowdhury, and A. W. Wolkoff The Human Organic Anion Transport Protein SLC21A6 Is Not Sufficient for Bilirubin Transport J. Biol. Chem., May 30, 2003; 278(23): 20695 - 20699. [Abstract] [Full Text] [PDF]

				S. D. Zucker, W. Goessling, E. J. Bootle, and C. Sterritt Localization of bilirubin in phospholipid bilayers by parallax analysis of fluorescence quenching J. Lipid Res., September 1, 2001; 42(9): 1377 - 1388. [Abstract] [Full Text] [PDF]

				W. Goessling and S. D. Zucker Role of apolipoprotein D in the transport of bilirubin in plasma Am J Physiol Gastrointest Liver Physiol, August 1, 2000; 279(2): G356 - G365. [Abstract] [Full Text] [PDF]

				E. Battaglia and J. Gollan A Unique Multifunctional Transporter Translocates Estradiol-17beta -Glucuronide in Rat Liver Microsomal Vesicles J. Biol. Chem., June 22, 2001; 276(26): 23492 - 23498. [Abstract] [Full Text] [PDF]