Bile salt-dependent pathway

Bile is produced by the hepatocytes and modified by the cholan-giocytes that line the bile ducts. Adults produce approximately 400-800 mL of bile daily. The bile salt-dependent pathway produces approximately 225 mL/day, the bile salt-independent pathway produces approximately 225 mL/day, and cholangiocytes produce a further 150 mL/day. 

The bile salt-dependent pathway relies on conjugated bile salts being excreted from the hepatocytes into the hepatic canaliculi via the... 

Stimulation of bile flow in the biliary system. The bile salt-dependent pathway, which allows bile flow, is described above. 

The bile salt-independent pathway depends on osmotically active solutes such as glutathione and bicarbonate to generate water flow into the canaliculi. It has been shown that bile flow continues at zero bile salt excretion, i.e. a bile salt-independent process. 

Utilising a reversion assay in Salmonella enterica, Prieto et al reported an increased frequency of point mutations following bile-salt exposure. Mutations were predominantly nucleotide substitutions (GC to AT transitions) and -1 frameshift mutations.The frameshifts were dependent on SOS induction and linked to the activity of DinB polymerase (Pol IV). The authors proposed that the GC to AT transitions stimulated by bile, could have arisen from oxidative processes giving rise to oxidised cytosine residues. Consistent with this hypothesis, the authors demonstrated that strains of S. enterica-lacking enzymes required for base-excision repair (endonuclease III and exonuclease IV) and the removal of oxidised bases, demonstrated increased bile-acid sensitivity compared with competent strains. In another study using E. coli, resistance to the DNA-damaging effects of bile was associated with Dam-directed mismatch repair, a pathway also involved with the repair of oxidative DNA lesions. ... 

Michel WC (1999) Cyclic nucleotide-gated channel activation is not required for activity-dependent labeling of zebrafish olfactory receptor neurons by amino adds. Biol Signals Recept 8 338-347 Michel WC, Derbidge DS (1997) Evidence of distinct amino acid and bile salt receptors in the olfactory system of the zebrafish, Danio rerio. Brain Res 764 179-187 Michel WC, Sanderson MJ, Olson JK, Lipschitz DL (2003) Evidence of a novel transduction pathway mediating detection of polyamines by the zebrafish olfactory system. J Exp Biiol 206 1697-1706... 

Dietary riboflavin is present mostly as a phosphate, which is rapidly hydrolyzed before absorption in the duodenum.In humans, the rapid, saturable absorption of riboflavin following an oral dose suggests that it is transported by a carrier-mediated pathway located predominantly in duodenal enterocytes. The process may be sodium-dependent. Bile salts enhance absorption of riboflavin. Fecal riboflavin is derived from the intestinal mucosa and the intestinal flora. This is the predominant excretory route for the vitamin. 

BSEP is a liver-specific and ATP-dependent transport protein that mediates the excretion of bile salts into bile and is expressed on the apical plasma membrane domain (canalicular surface) of hepatocytes (Lam et al., 2010). Bile formation and excretion is an essential biological process in higher vertebrates and is an important route of xenobiotic elimination, which also plays a key role in intestinal dissolution and absorption of lipids, vitamins, and fat-soluble food components. Bile salts are synthesized within hepatocytes by cytochrome P450-mediated metabolism of cholesterol and are key components of bile (Hofmann and Hagey, 2008). Bile formation and bile flow are regulated physiologically by complex mechanisms, which in hepatocytes include nuclear hormone receptor-mediated transcriptional pathways and a variety of posttranscriptional processes (Kullak-Ublick et al., 2004 Gonzalez, 2012). 

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