Physiological and molecular biochemical mechanisms of bile formation

Figure 7 Mechanisms of the transport of bile acids, water, and electrolytes through the hepatocyte (transcellular pathway) and intercellular space (paracellular pathway). Localization and function of sinusoidal and canalicular hepatocellular transporters. The Na⁺-dependent sinusoidal uptake of bile salts (BS) is mediated by Na⁺-dependent taurocholate cotransport peptide. The Na⁺-independent hepatic uptake of organic anions (OA^-), BSs and type II organic cations (OC⁺) is mediated by members of the OATP family. Sinusoidal uptake of type I OC⁺ is mediated by OCT1. Transport across the canalicular membrane is driven mainly by ATP-dependent export pumps. MDR1 mediates canalicular excretion of amphiphilic type II OC⁺ and other hydrophobic compounds. MDR3 functions as a PC flippase. BSEP mediates apical excretion of BSs. MRP2 transports non-bile-salt organic anions, such as bilirubin glucuronides (BGs), GSH, and sulfated/glucuronidated bile salts. Canalicular transport of HCO₃^- is mediated by the Cl^-/HCO₃^- exchanger AE2. AQP9 and AQP8 are involved in the transport of water across the sinusoidal and the canalicular membrane, respectively. The nature of the water channels in human liver has been characterized[84]. GC: Golgi apparatus (complex); ER: Endoplasmic reticulum; N: Nucleus.