Bile alcohols mammals

In 1974, Setoguchi et al. found that patients with cerebrotendinous xanthomatosis had an impaired sjTithesis of bile acids and excreted large amounts of C27 bile alcohols in bile and feces [76]. Since then, a number of investigations have revealed the occurrence of bile alcohols in mammals. It is now recognized that, when new analytical methods are applied, traces of bile alcohols can be detected even in biological fluids from healthy humans. Table 3 lists all the known bile alcohols identified in mammals. 

Since bile alcohols in mammals may be present in unconjugated form or as glucuronides or sulfate esters, studies of these compounds require techniques for group separation of the different forms. Ion-exchange chromatography has been used for this purpose [77-79]. Bile alcohol glucuronides may be deconjugated by... 

Trace amounts of bile alcohols resembling those excreted in CTX and in the patient with cholestasis were found in the bile of normal rabbit [93]. The following compounds were identified 5 -cholestane-3a,7a,12a,25,26-pentol 5j8-cholestane-3o,7a,12 ,25-tetrol (245)-5 - and 5 8-cholestane-3a,7a,12a,24-tetrols 24-nor-5)8-cholestane-3a,7a,12 .25-tetrol [93]. This result and our unpublished observations on the presence of bile alcohols in the bile of healthy humans suggest that bile alcohols can be produced even in healthy mammals although in much smaller quantities. 

VI) Metabolism of bile alcohols and primitive bile acids in mammals... 

The natural distribution and the chemical structure of bile alcohols and primitive bile acids indicate that these compounds found in lower vertebrates are evolutionary precursors of the common bile acids found in mammalian species. Haslewood proposed that the mechanism of conversion of cholesterol to the common bile acids in mammals is a recapitulation of the evolution of bile salts and thus would entail the intermediary formation of bile alcohols and primitive bile adds similar to or the same as those found in lower species [120]. Thus, studies have been carried out to test whether the naturally occurring bile alcohols and primitive bile acids are intermediates in the biosynthetic pathway between cholesterol and the C24 bile acids in mammals. There is no doubt that such studies contributed to the elucidation of the sequence of reactions in the biosynthesis of the mammalian C24 bile acids. 

Studies on the biosynthesis of bile alcohols and primitive bile acids in lower vertebrates will provide additional information on the formation of the common bile acids in mammals and will help to clarify the molecular evolution of bile salts. However, such studies have been carried out only in a few species of lower vertebrates. 

Bile adds components of bile which serve as emuldfying agents. They are steroid carboxylic adds linked to taurine or glycine by a peptide bond. According to the constituent amino add, they are called glycocholic or taurocholic acids. Ihe former predominate in human and bovine bile, the latter in canine bile. B. a. are characteristic of mammals in lower vertebrates the same function is performed by Bile alcohols (see). In mammals, the pattern of B.a. is often spedfic for the spedes. 

Phosphates of pharmaceutical interest are often monoesters (Sect. 9.3), and the enzymes that are able to hydrolyze them include alkaline and acid phosphatases. Alkaline phosphatase (alkaline phosphomonoesterase, EC 3.1.3.1) is a nonspecific esterase of phosphoric monoesters with an optimal pH for catalysis of ca. 8 [140], In the presence of a phosphate acceptor such as 2-aminoethanol, the enzyme also catalyzes a transphosphorylation reaction involving transfer of the phosphoryl group to the alcohol. Alkaline phosphatase is bound extracellularly to membranes and is widely distributed, in particular in the pancreas, liver, bile, placenta, and osteoplasts. Its specific functions in mammals remain poorly understood, but it seems to play an important role in modulation by osteoplasts of bone mineralization. 

Sterols and Cholesterol. Natural sterols are crystalline C76 C1(1 steroid alcohols containing an aliphatic side chain at C17. Sterols were first isolated as lionsaponifiable fractions of lipids from various plant and animal sources and have been identified in almost all types of living organisms. By far, the most common sterol in vertebrates is cholesterol (8). Cholesterol serves two principal functions in mammals. First, cholesterol plays a role in the structure and function of biological membranes.. Secondly, cholesterol serves as a central intermediate in the biosynthesis of many biologically active steroids, including bile acids, corticosteroids, and sex hormones. 

Among the sterols of the least specialized animals we find Cgg or compounds. Sterols of this type differ in the type and degree of unsaturation, and in the nature of the radical attached at C-24, etc. (Bergmann, 1952). On the other hand, from a series of studies by Haslewood and co-workers, we see that in teleost fishes or Elasmobranchs, Amphibians, crocodiles and alligators, in a lizard, in Chelonians (turtles and tortoises) and in some birds, the bile salts contain C27, Cjg (or possibly Cgg) alcohols and acids whilst in snakes and mammals, substances of this type are not found. But the presence of Cgg bile acids has been demonstrated in snakes, teleost fishes, mammals and birds, but not in Elasmobranchs, Batracians or reptiles such as the Crocodilians and the Chelonians. 

Sterols are a class of lipids containing a common steroid core of a fused four-ring structure with a hydrocarbon side chain and an alcohol group. Cholesterol is the primary sterol lipid in mammals and is an important constituent of cellular membranes. Oxidization and/or metabolism of cholesterol yield numerous oxysterols, steroids, bile acids, etc., many of which are important signaling molecules in biological systems. Cholesteryl esters esterified with a variety of fatty acyls are enriched in... 

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