Unknown

Dataset Information

0

Rotor Syndrome: Glucuronidated Bile Acidemia From Defective Reuptake by Hepatocytes.


ABSTRACT: Organic anion transporting polypeptide (OATP) 1B1 (gene, solute carrier organic anion transporter family member 1B1 [SLCO1B1]) and OATP1B3 (SLCO1B3) serve as transporters for hepatic uptake of important endogenous substances and several commonly prescribed drugs. Inactivation of both proteins together causes Rotor syndrome. How this OATP1B1/1B3 defect disturbs bile acid (BA) metabolism is largely unknown. In this study, we performed detailed BA analysis in 3 patients with genetically diagnosed Rotor syndrome. We found that BAs glucuronidated at the C-3 position (BA-3G) accounted for 50% or more of total BAs in these patients. In contrast but similarly to healthy controls, only trace amounts of BA-3G were detected in patients with constitutional indocyanine green excretory defect (OATP1B3 deficiency) or sodium-taurocholate cotransporting polypeptide (NTCP; gene, solute carrier family 10 member 1 [SLC10A1]) deficiency. Therefore, substantial amounts of BA-3G are synthesized in hepatocytes. The cycling pathway of BA-3G, consisting of excretion from upstream hepatocytes and uptake by downstream hepatocytes by OATP1B1/1B3 may exist to reduce the burden on upstream hepatocytes. Conclusion: Detailed BA analysis revealed glucuronidated bile acidemia in patients with Rotor syndrome. Further exploration of the physiologic role of glucuronidated BAs is necessary.

SUBMITTER: Kimura A 

PROVIDER: S-EPMC8034574 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC9780789 | biostudies-literature
| S-EPMC3266790 | biostudies-literature
| S-EPMC7469617 | biostudies-literature
2012-01-16 | GSE33733 | GEO
| S-EPMC7337260 | biostudies-literature
2012-01-16 | E-GEOD-33733 | biostudies-arrayexpress
| S-EPMC4750580 | biostudies-other
| S-EPMC7073417 | biostudies-literature
| S-EPMC4852394 | biostudies-literature
| S-EPMC7288213 | biostudies-literature