2.A.65 The Bilirubin Transporter (BRT) Family
The BRT family consists of a single protein, the 'bilitranslocase', a hepatic plasma membrane bilirubin transporter involved in the uptake of bilirubin and other organic anions from the blood into liver cells. The protein contains a bilirubin-binding motif, and it binds bilirubin with exceptionally high affinity (2 nM) (Battiston et al., 1998). This motif is also present in α-phycocyanines, biliproteins present in cyanobacteria. BRT also takes up a variety of cholephilic organic anions such as bromosulphophthalein (BSP), the related phthalein thymol blue, the antibiotic, rifamycin, and the vitamin precursor, nicotinic acid (Župerl et al., 2011). Sulfobromophthalein has been shown to be transported electrogenically (Passamonti et al., 2005). The carrier may exist in two interchangeable forms with high (5 μM for BSP) and low (37 μM for BSP) affinities for its substrates. Phenylmethylsulfonyl fluoride inactivates bilitranslocase (Passamonti et al., 1999).
The bilitranslocase exhibits 3-5 peaks of hydrophobicity, each of a length sufficient to pass through the membrane as an α-helix. The first is a 'certain' transmembrane α-helix spanner (TMS) according to the TopPred program, and the amphipathicity of two more have been reported (Choudhury et al. 2013). The topology is therefore uncertain. The rat bilitranslocase shows sequence similarity with no other protein in the NCBI database as of July 2012, not even in mice or humans. However, it may be more wide spread (Petrussa et al., 2010). One of the putative TMSs has been shown to be α-helical (Perdih et al., 2012). Rat liver shows increased expression of bilitranslocase from animals with obstructive cholestasis (Brandoni et al., 2010). Bilitranslocase mediates the uptake of some flavenoids such as cyanidin-3-glucoside which may have a protective effect against oxidative stress (Ziberna et al., 2012).
The presumed transport reaction catalyzed by bilitranslocase is:
Bilirubin (out) + nNa+ (out) → bilirubin (in) + nNa+ (in)