Review
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World J Gastroenterol. Oct 14, 2013; 19(38): 6398-6407
Published online Oct 14, 2013. doi: 10.3748/wjg.v19.i38.6398
New insights in bilirubin metabolism and their clinical implications
Eva Sticova, Milan Jirsa
Eva Sticova, Milan Jirsa, Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague 4, Czech Republic
Eva Sticova, Third Faculty of Medicine, Charles University, 10000 Prague 10, Czech Republic
Author contributions: Sticova E wrote the manuscript; Jirsa M edited the manuscript.
Supported by The Project (Ministry of Health, Czech Republic) for Development of Research Organization 00023001 (IKEM, Prague, Czech Republic), Institutional support
Correspondence to: Sticova Eva, MD, Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech Republic. eva.sticova@ikem.cz
Telephone: +420-236-055229 Fax: +420-241-721666
Received: April 28, 2013
Revised: July 18, 2013
Accepted: August 8, 2013
Published online: October 14, 2013
Processing time: 170 Days and 13.4 Hours
Core Tip

Core tip: Experiments with Oatp1a/1b-null mice and Oatp1a/1b; Abcc3 combination knockout mice plainly demonstrated that even under physiologic conditions a substantial portion of bilirubin glucuronides is not excreted directly into bile but is transported back to the blood by Abcc3. Oatp1a/1b activity accentuated in downstream (centrizonal) hepatocytes allows efficient reuptake of bilirubin conjugates, with a subsequent possibility being safely eliminated by excretion into bile. This and molecular findings in Rotor syndrome suggest that human transporters MRP3 and OATP1Bs form a sinusoidal liver-to-blood cycle which mediates shifting (hopping) of bilirubin and other substrates from periportal to centrizonal hepatocytes (References 18, 19, 22, 125).