Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology, and Therapeutics

Abstract

Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease.

Olfactory sensitivity to bile fluid and bile salts in the European eel (Anguilla anguilla), goldfish (Carassius auratus) and Mozambique tilapia (Oreochromis mossambicus) suggests a `broad range' sensitivity not confined to those produced by conspecifics alone

“…The evolutionary history of bile salts is characterized by a process of progressive oxidation and carbon loss, from sulphated C 27 bile alcohols to taurine-conjugated C 24 bile acids (Haslewood, 1967;Hofmann and Hagey, 2008). However, the immature eel is quite unusual, in that its immature form uses taurine-conjugated C 24 bile acids, but at sexual maturation, it goes through an apparent regression back to C 27 bile alcohol forms, a process hitherto unseen in any vertebrate group.…”

“…Bile salts, which are a key constituent of bile, are steroidal compounds with a characteristic fused four-carbon-ring skeleton often found conjugated with glycine, taurine, cysteine or sulphate groups (Goto et al, 2003;Hofmann, 1999;Moschetta et al, 2005). In modern mammals, bile salts are mostly C 24 carboxylic acids, whereas in primitive mammals, cartilaginous fish and reptiles, C 27 acids and alcohols are found (Haslewood, 1967;Hofmann and Hagey, 2008;Moschetta et al, 2005).…”

Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls

“…[1][2][3] Chemically they share a steroidal skeleton with an unusual cis fusion between rings A and B, a short lateral chain ending in a carboxylic moiety and different numbers of hydroxyl groups on the α-face. These structural characteristics contribute to their facial amphiphilia, associated with a convex hydrophobic α-face and a concave and hydrophilic β-face (Fig.…”

Recent insights into the function and regulation of the bile salt export pump (ABCB11)

“…The gall bladder is a concentration and storage device for bile salts and other bile constituents (1). Thereafter, bile salts enter the duodenum, where they assist in the absorption of lipids and fat soluble vitamins.…”

“…There, bile salts are taken up from the sinusoidal blood plasma by hepatocytes, where their journey starts again. This process of bile salt circling through the gut to the liver is known as enterohepatic circulation (1)(2)(3)(4).…”